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Obat antivirusObat antivirus
VirusVirusParasit intraseluler obligat dimana virus tersebut memanfaatkan
enzim-enzim metabolik dari sel inang ribosom inang untuk sintesis protein
Kehidupannya sangat tergantung pada sel inang Tak ada yang dapat dibuatnya tanpa sel inang
Struktur virusStruktur virusPartikel virus (virion) terdiri dari
bagian-bagian berikut
1048708 inti asam nukleat DNA or RNA1048708 sering terdapat enzim spesifik
virus1048708 ditutupi oleh protein ldquocapsidrdquo 1048708 kadang-kadang terdapat lipid
pada lapisan terluar ldquoenveloperdquo
Klasifikasi virusKlasifikasi virusDNA viruses
Contain an DNA genome Virus replication
ndash DNA polymerase Examples
ndash Herpes Virusndash Hepatitis B virusndash Epstein-Barr virus
RNA Viruses Contain an RNA genome Virus replication
ndash RNA-dependent RNA polymerasendash Reverse transcriptase
(Retroviruses) Examples
ndash Rubella virusndash Dengue fever virusHepatitis A
virusndash Hepatitis C virusndash HIVndash Influenza virus
Siklus hidup
1Attachment melekatnya virus pada reseptor yang terdapat pada permukaan sel inang
2Entry masuknya virus melewati membran sel inang 3Uncoating uncoating asam nukleat virus4Replication sintesis protein pengatur awal ( cth asam nukleat polimerase sintesis virus baru RNA or DNA sintesis protein pembentuk struktur5 Assembly (maturation) pematangan partikel virus 6 Release pelepasan dari sel
1 2 3
6
5
4
78
bull Banyak virus menginfeksi sel inang spesifik
bull Banyak infeksi virus bersifat self limiting tidak memerlukan pengobatan cth common cold yang disebabkan oleh rinovirus
bull Infeksi virus yang umum seperti influenza chicken pox mumps biasanya dapat diatasi oleh sistem imun tubuh
Virus lain dapat menyebabkan penyakit serius dan fatal sehingga memerlukan pengobatan yang agresif cth HIV (AIDS)
Poin penting
Virus Genera Nucleic Acid Clinical Illness
Adenovirus DNA URTIs Eye infections
Hepadnaviridae DNA Hepatitis B Cancer ()
Herpesvirus DNA Genital herpes Varicella Encephalitis Retinitis
Papillomavirus DNA Papilloma Cancer
Parvovirus DNA Erythema infectiosum
Arenavirus RNA Lymphocytic choriomeningitis
Bunyavirus RNA Encephalitis
Coronavirus RNA URTIs
Influenzavirus RNA Influenza
Paramyxovirus RNA Measles URTIs
Picornavirus RNA Poliomyelitis diarrhea URTIs
Retrovirus RNA Leukemia AIDS
Rhabdovirus RNA Rabies
Togavirus RNA Rubella Yellow fever
Virus Groups of Clinical Importance
Obat anti virusObat anti virus Vaksin sering digunakan untuk membangun
sistem kekebalan sebelum infeksi virus terjadi
Agar efektif antivirus harus dapat menghambat entry atau keluarya virus ke sel inang atau aktif di dalam sel inang
9
Tantangan terapi anti virus replikasi virus yang cepat menyebabkan
sulitnya mengembangkan anti virus yang efektif
Virus dapat bermutasi dengan cepat obat menjadi tidak efektif
Kesulitan obat menemukan virus tanpa mengganggu sel normal inang
10
ANTI-HERPES ANTI VZVANTI-HERPES ANTI VZV
HSV = herpes simplex virusHSV = herpes simplex virusVZV = Varicella Zoster virusVZV = Varicella Zoster virus
ACYCLOVIRACYCLOVIR
Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV
(ebstein bar virus) CMV (cytomegalo virus)
Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi
FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan
dosis BA relatif meningkat sampai 70 setelah
pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk
cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan
plasenta Absorbsi perkutan rendah
Penggunaan dalam terapiPenggunaan dalam terapi
Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg
3xhari
THERAPEUTIC USESTHERAPEUTIC USES
ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS
Efek sampingEfek samping
Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital
ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas
IV- insufisiensi ginjal CNS
PENCICLOVIRPENCICLOVIR
Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV
Aktif terhadap HBV (hepatiis B virus)
MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine
kinase Penciclovir trifosfat merupakan inhibitor
kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir
tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi
Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7
hari seara dengan asiklovir utk infeksi mucocutaneous HSV
Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV
Efek sampingEfek samping
Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak
teridentifikasi
DRUG MECHANISMVIRAL
SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Acylovir Metabolized by thymidine kinase to triphosphate
Herpes simplex 1 amp 2 varicella zoster
Produce abnormal thymidine kinase
Skin irritation burning crystalline nephropathy
IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction
Pencyclovir Oral HSV (coldsores)
Topical
Valacyclovir L-valyl ester of acyclovir converted to acyclovir
Herpes zoster (shingles)
Nausea headache PO Slightly better oral absorption than acyclovir
No clear advantage over acyclovir
Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks
Herpes simplex keratitis No effect on RNA viruses
Resistance develops
Photophobia irritation of conjunctiva amp eyelid
Eyedrops Drug is a halogenated derivative of deoxyuridine
Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate
Shortens duration of herpes zoster amp genital herpes
Minimal toxicity Headache
PO Decrease dose with renal dysfunction
Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells
CMV retinitis amp severe systemic CMV infections
Some resistant strains lack thymidine kinase Cannot activate drug
Granulocytopenia thrombocytopenia
IVPO Excreted unchanged in urine Decrease dose with renal dysfunction
Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)
ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
VirusVirusParasit intraseluler obligat dimana virus tersebut memanfaatkan
enzim-enzim metabolik dari sel inang ribosom inang untuk sintesis protein
Kehidupannya sangat tergantung pada sel inang Tak ada yang dapat dibuatnya tanpa sel inang
Struktur virusStruktur virusPartikel virus (virion) terdiri dari
bagian-bagian berikut
1048708 inti asam nukleat DNA or RNA1048708 sering terdapat enzim spesifik
virus1048708 ditutupi oleh protein ldquocapsidrdquo 1048708 kadang-kadang terdapat lipid
pada lapisan terluar ldquoenveloperdquo
Klasifikasi virusKlasifikasi virusDNA viruses
Contain an DNA genome Virus replication
ndash DNA polymerase Examples
ndash Herpes Virusndash Hepatitis B virusndash Epstein-Barr virus
RNA Viruses Contain an RNA genome Virus replication
ndash RNA-dependent RNA polymerasendash Reverse transcriptase
(Retroviruses) Examples
ndash Rubella virusndash Dengue fever virusHepatitis A
virusndash Hepatitis C virusndash HIVndash Influenza virus
Siklus hidup
1Attachment melekatnya virus pada reseptor yang terdapat pada permukaan sel inang
2Entry masuknya virus melewati membran sel inang 3Uncoating uncoating asam nukleat virus4Replication sintesis protein pengatur awal ( cth asam nukleat polimerase sintesis virus baru RNA or DNA sintesis protein pembentuk struktur5 Assembly (maturation) pematangan partikel virus 6 Release pelepasan dari sel
1 2 3
6
5
4
78
bull Banyak virus menginfeksi sel inang spesifik
bull Banyak infeksi virus bersifat self limiting tidak memerlukan pengobatan cth common cold yang disebabkan oleh rinovirus
bull Infeksi virus yang umum seperti influenza chicken pox mumps biasanya dapat diatasi oleh sistem imun tubuh
Virus lain dapat menyebabkan penyakit serius dan fatal sehingga memerlukan pengobatan yang agresif cth HIV (AIDS)
Poin penting
Virus Genera Nucleic Acid Clinical Illness
Adenovirus DNA URTIs Eye infections
Hepadnaviridae DNA Hepatitis B Cancer ()
Herpesvirus DNA Genital herpes Varicella Encephalitis Retinitis
Papillomavirus DNA Papilloma Cancer
Parvovirus DNA Erythema infectiosum
Arenavirus RNA Lymphocytic choriomeningitis
Bunyavirus RNA Encephalitis
Coronavirus RNA URTIs
Influenzavirus RNA Influenza
Paramyxovirus RNA Measles URTIs
Picornavirus RNA Poliomyelitis diarrhea URTIs
Retrovirus RNA Leukemia AIDS
Rhabdovirus RNA Rabies
Togavirus RNA Rubella Yellow fever
Virus Groups of Clinical Importance
Obat anti virusObat anti virus Vaksin sering digunakan untuk membangun
sistem kekebalan sebelum infeksi virus terjadi
Agar efektif antivirus harus dapat menghambat entry atau keluarya virus ke sel inang atau aktif di dalam sel inang
9
Tantangan terapi anti virus replikasi virus yang cepat menyebabkan
sulitnya mengembangkan anti virus yang efektif
Virus dapat bermutasi dengan cepat obat menjadi tidak efektif
Kesulitan obat menemukan virus tanpa mengganggu sel normal inang
10
ANTI-HERPES ANTI VZVANTI-HERPES ANTI VZV
HSV = herpes simplex virusHSV = herpes simplex virusVZV = Varicella Zoster virusVZV = Varicella Zoster virus
ACYCLOVIRACYCLOVIR
Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV
(ebstein bar virus) CMV (cytomegalo virus)
Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi
FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan
dosis BA relatif meningkat sampai 70 setelah
pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk
cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan
plasenta Absorbsi perkutan rendah
Penggunaan dalam terapiPenggunaan dalam terapi
Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg
3xhari
THERAPEUTIC USESTHERAPEUTIC USES
ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS
Efek sampingEfek samping
Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital
ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas
IV- insufisiensi ginjal CNS
PENCICLOVIRPENCICLOVIR
Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV
Aktif terhadap HBV (hepatiis B virus)
MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine
kinase Penciclovir trifosfat merupakan inhibitor
kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir
tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi
Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7
hari seara dengan asiklovir utk infeksi mucocutaneous HSV
Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV
Efek sampingEfek samping
Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak
teridentifikasi
DRUG MECHANISMVIRAL
SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Acylovir Metabolized by thymidine kinase to triphosphate
Herpes simplex 1 amp 2 varicella zoster
Produce abnormal thymidine kinase
Skin irritation burning crystalline nephropathy
IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction
Pencyclovir Oral HSV (coldsores)
Topical
Valacyclovir L-valyl ester of acyclovir converted to acyclovir
Herpes zoster (shingles)
Nausea headache PO Slightly better oral absorption than acyclovir
No clear advantage over acyclovir
Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks
Herpes simplex keratitis No effect on RNA viruses
Resistance develops
Photophobia irritation of conjunctiva amp eyelid
Eyedrops Drug is a halogenated derivative of deoxyuridine
Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate
Shortens duration of herpes zoster amp genital herpes
Minimal toxicity Headache
PO Decrease dose with renal dysfunction
Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells
CMV retinitis amp severe systemic CMV infections
Some resistant strains lack thymidine kinase Cannot activate drug
Granulocytopenia thrombocytopenia
IVPO Excreted unchanged in urine Decrease dose with renal dysfunction
Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)
ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
Struktur virusStruktur virusPartikel virus (virion) terdiri dari
bagian-bagian berikut
1048708 inti asam nukleat DNA or RNA1048708 sering terdapat enzim spesifik
virus1048708 ditutupi oleh protein ldquocapsidrdquo 1048708 kadang-kadang terdapat lipid
pada lapisan terluar ldquoenveloperdquo
Klasifikasi virusKlasifikasi virusDNA viruses
Contain an DNA genome Virus replication
ndash DNA polymerase Examples
ndash Herpes Virusndash Hepatitis B virusndash Epstein-Barr virus
RNA Viruses Contain an RNA genome Virus replication
ndash RNA-dependent RNA polymerasendash Reverse transcriptase
(Retroviruses) Examples
ndash Rubella virusndash Dengue fever virusHepatitis A
virusndash Hepatitis C virusndash HIVndash Influenza virus
Siklus hidup
1Attachment melekatnya virus pada reseptor yang terdapat pada permukaan sel inang
2Entry masuknya virus melewati membran sel inang 3Uncoating uncoating asam nukleat virus4Replication sintesis protein pengatur awal ( cth asam nukleat polimerase sintesis virus baru RNA or DNA sintesis protein pembentuk struktur5 Assembly (maturation) pematangan partikel virus 6 Release pelepasan dari sel
1 2 3
6
5
4
78
bull Banyak virus menginfeksi sel inang spesifik
bull Banyak infeksi virus bersifat self limiting tidak memerlukan pengobatan cth common cold yang disebabkan oleh rinovirus
bull Infeksi virus yang umum seperti influenza chicken pox mumps biasanya dapat diatasi oleh sistem imun tubuh
Virus lain dapat menyebabkan penyakit serius dan fatal sehingga memerlukan pengobatan yang agresif cth HIV (AIDS)
Poin penting
Virus Genera Nucleic Acid Clinical Illness
Adenovirus DNA URTIs Eye infections
Hepadnaviridae DNA Hepatitis B Cancer ()
Herpesvirus DNA Genital herpes Varicella Encephalitis Retinitis
Papillomavirus DNA Papilloma Cancer
Parvovirus DNA Erythema infectiosum
Arenavirus RNA Lymphocytic choriomeningitis
Bunyavirus RNA Encephalitis
Coronavirus RNA URTIs
Influenzavirus RNA Influenza
Paramyxovirus RNA Measles URTIs
Picornavirus RNA Poliomyelitis diarrhea URTIs
Retrovirus RNA Leukemia AIDS
Rhabdovirus RNA Rabies
Togavirus RNA Rubella Yellow fever
Virus Groups of Clinical Importance
Obat anti virusObat anti virus Vaksin sering digunakan untuk membangun
sistem kekebalan sebelum infeksi virus terjadi
Agar efektif antivirus harus dapat menghambat entry atau keluarya virus ke sel inang atau aktif di dalam sel inang
9
Tantangan terapi anti virus replikasi virus yang cepat menyebabkan
sulitnya mengembangkan anti virus yang efektif
Virus dapat bermutasi dengan cepat obat menjadi tidak efektif
Kesulitan obat menemukan virus tanpa mengganggu sel normal inang
10
ANTI-HERPES ANTI VZVANTI-HERPES ANTI VZV
HSV = herpes simplex virusHSV = herpes simplex virusVZV = Varicella Zoster virusVZV = Varicella Zoster virus
ACYCLOVIRACYCLOVIR
Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV
(ebstein bar virus) CMV (cytomegalo virus)
Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi
FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan
dosis BA relatif meningkat sampai 70 setelah
pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk
cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan
plasenta Absorbsi perkutan rendah
Penggunaan dalam terapiPenggunaan dalam terapi
Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg
3xhari
THERAPEUTIC USESTHERAPEUTIC USES
ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS
Efek sampingEfek samping
Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital
ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas
IV- insufisiensi ginjal CNS
PENCICLOVIRPENCICLOVIR
Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV
Aktif terhadap HBV (hepatiis B virus)
MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine
kinase Penciclovir trifosfat merupakan inhibitor
kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir
tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi
Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7
hari seara dengan asiklovir utk infeksi mucocutaneous HSV
Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV
Efek sampingEfek samping
Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak
teridentifikasi
DRUG MECHANISMVIRAL
SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Acylovir Metabolized by thymidine kinase to triphosphate
Herpes simplex 1 amp 2 varicella zoster
Produce abnormal thymidine kinase
Skin irritation burning crystalline nephropathy
IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction
Pencyclovir Oral HSV (coldsores)
Topical
Valacyclovir L-valyl ester of acyclovir converted to acyclovir
Herpes zoster (shingles)
Nausea headache PO Slightly better oral absorption than acyclovir
No clear advantage over acyclovir
Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks
Herpes simplex keratitis No effect on RNA viruses
Resistance develops
Photophobia irritation of conjunctiva amp eyelid
Eyedrops Drug is a halogenated derivative of deoxyuridine
Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate
Shortens duration of herpes zoster amp genital herpes
Minimal toxicity Headache
PO Decrease dose with renal dysfunction
Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells
CMV retinitis amp severe systemic CMV infections
Some resistant strains lack thymidine kinase Cannot activate drug
Granulocytopenia thrombocytopenia
IVPO Excreted unchanged in urine Decrease dose with renal dysfunction
Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)
ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
Klasifikasi virusKlasifikasi virusDNA viruses
Contain an DNA genome Virus replication
ndash DNA polymerase Examples
ndash Herpes Virusndash Hepatitis B virusndash Epstein-Barr virus
RNA Viruses Contain an RNA genome Virus replication
ndash RNA-dependent RNA polymerasendash Reverse transcriptase
(Retroviruses) Examples
ndash Rubella virusndash Dengue fever virusHepatitis A
virusndash Hepatitis C virusndash HIVndash Influenza virus
Siklus hidup
1Attachment melekatnya virus pada reseptor yang terdapat pada permukaan sel inang
2Entry masuknya virus melewati membran sel inang 3Uncoating uncoating asam nukleat virus4Replication sintesis protein pengatur awal ( cth asam nukleat polimerase sintesis virus baru RNA or DNA sintesis protein pembentuk struktur5 Assembly (maturation) pematangan partikel virus 6 Release pelepasan dari sel
1 2 3
6
5
4
78
bull Banyak virus menginfeksi sel inang spesifik
bull Banyak infeksi virus bersifat self limiting tidak memerlukan pengobatan cth common cold yang disebabkan oleh rinovirus
bull Infeksi virus yang umum seperti influenza chicken pox mumps biasanya dapat diatasi oleh sistem imun tubuh
Virus lain dapat menyebabkan penyakit serius dan fatal sehingga memerlukan pengobatan yang agresif cth HIV (AIDS)
Poin penting
Virus Genera Nucleic Acid Clinical Illness
Adenovirus DNA URTIs Eye infections
Hepadnaviridae DNA Hepatitis B Cancer ()
Herpesvirus DNA Genital herpes Varicella Encephalitis Retinitis
Papillomavirus DNA Papilloma Cancer
Parvovirus DNA Erythema infectiosum
Arenavirus RNA Lymphocytic choriomeningitis
Bunyavirus RNA Encephalitis
Coronavirus RNA URTIs
Influenzavirus RNA Influenza
Paramyxovirus RNA Measles URTIs
Picornavirus RNA Poliomyelitis diarrhea URTIs
Retrovirus RNA Leukemia AIDS
Rhabdovirus RNA Rabies
Togavirus RNA Rubella Yellow fever
Virus Groups of Clinical Importance
Obat anti virusObat anti virus Vaksin sering digunakan untuk membangun
sistem kekebalan sebelum infeksi virus terjadi
Agar efektif antivirus harus dapat menghambat entry atau keluarya virus ke sel inang atau aktif di dalam sel inang
9
Tantangan terapi anti virus replikasi virus yang cepat menyebabkan
sulitnya mengembangkan anti virus yang efektif
Virus dapat bermutasi dengan cepat obat menjadi tidak efektif
Kesulitan obat menemukan virus tanpa mengganggu sel normal inang
10
ANTI-HERPES ANTI VZVANTI-HERPES ANTI VZV
HSV = herpes simplex virusHSV = herpes simplex virusVZV = Varicella Zoster virusVZV = Varicella Zoster virus
ACYCLOVIRACYCLOVIR
Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV
(ebstein bar virus) CMV (cytomegalo virus)
Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi
FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan
dosis BA relatif meningkat sampai 70 setelah
pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk
cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan
plasenta Absorbsi perkutan rendah
Penggunaan dalam terapiPenggunaan dalam terapi
Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg
3xhari
THERAPEUTIC USESTHERAPEUTIC USES
ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS
Efek sampingEfek samping
Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital
ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas
IV- insufisiensi ginjal CNS
PENCICLOVIRPENCICLOVIR
Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV
Aktif terhadap HBV (hepatiis B virus)
MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine
kinase Penciclovir trifosfat merupakan inhibitor
kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir
tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi
Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7
hari seara dengan asiklovir utk infeksi mucocutaneous HSV
Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV
Efek sampingEfek samping
Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak
teridentifikasi
DRUG MECHANISMVIRAL
SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Acylovir Metabolized by thymidine kinase to triphosphate
Herpes simplex 1 amp 2 varicella zoster
Produce abnormal thymidine kinase
Skin irritation burning crystalline nephropathy
IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction
Pencyclovir Oral HSV (coldsores)
Topical
Valacyclovir L-valyl ester of acyclovir converted to acyclovir
Herpes zoster (shingles)
Nausea headache PO Slightly better oral absorption than acyclovir
No clear advantage over acyclovir
Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks
Herpes simplex keratitis No effect on RNA viruses
Resistance develops
Photophobia irritation of conjunctiva amp eyelid
Eyedrops Drug is a halogenated derivative of deoxyuridine
Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate
Shortens duration of herpes zoster amp genital herpes
Minimal toxicity Headache
PO Decrease dose with renal dysfunction
Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells
CMV retinitis amp severe systemic CMV infections
Some resistant strains lack thymidine kinase Cannot activate drug
Granulocytopenia thrombocytopenia
IVPO Excreted unchanged in urine Decrease dose with renal dysfunction
Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)
ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
Siklus hidup
1Attachment melekatnya virus pada reseptor yang terdapat pada permukaan sel inang
2Entry masuknya virus melewati membran sel inang 3Uncoating uncoating asam nukleat virus4Replication sintesis protein pengatur awal ( cth asam nukleat polimerase sintesis virus baru RNA or DNA sintesis protein pembentuk struktur5 Assembly (maturation) pematangan partikel virus 6 Release pelepasan dari sel
1 2 3
6
5
4
78
bull Banyak virus menginfeksi sel inang spesifik
bull Banyak infeksi virus bersifat self limiting tidak memerlukan pengobatan cth common cold yang disebabkan oleh rinovirus
bull Infeksi virus yang umum seperti influenza chicken pox mumps biasanya dapat diatasi oleh sistem imun tubuh
Virus lain dapat menyebabkan penyakit serius dan fatal sehingga memerlukan pengobatan yang agresif cth HIV (AIDS)
Poin penting
Virus Genera Nucleic Acid Clinical Illness
Adenovirus DNA URTIs Eye infections
Hepadnaviridae DNA Hepatitis B Cancer ()
Herpesvirus DNA Genital herpes Varicella Encephalitis Retinitis
Papillomavirus DNA Papilloma Cancer
Parvovirus DNA Erythema infectiosum
Arenavirus RNA Lymphocytic choriomeningitis
Bunyavirus RNA Encephalitis
Coronavirus RNA URTIs
Influenzavirus RNA Influenza
Paramyxovirus RNA Measles URTIs
Picornavirus RNA Poliomyelitis diarrhea URTIs
Retrovirus RNA Leukemia AIDS
Rhabdovirus RNA Rabies
Togavirus RNA Rubella Yellow fever
Virus Groups of Clinical Importance
Obat anti virusObat anti virus Vaksin sering digunakan untuk membangun
sistem kekebalan sebelum infeksi virus terjadi
Agar efektif antivirus harus dapat menghambat entry atau keluarya virus ke sel inang atau aktif di dalam sel inang
9
Tantangan terapi anti virus replikasi virus yang cepat menyebabkan
sulitnya mengembangkan anti virus yang efektif
Virus dapat bermutasi dengan cepat obat menjadi tidak efektif
Kesulitan obat menemukan virus tanpa mengganggu sel normal inang
10
ANTI-HERPES ANTI VZVANTI-HERPES ANTI VZV
HSV = herpes simplex virusHSV = herpes simplex virusVZV = Varicella Zoster virusVZV = Varicella Zoster virus
ACYCLOVIRACYCLOVIR
Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV
(ebstein bar virus) CMV (cytomegalo virus)
Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi
FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan
dosis BA relatif meningkat sampai 70 setelah
pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk
cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan
plasenta Absorbsi perkutan rendah
Penggunaan dalam terapiPenggunaan dalam terapi
Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg
3xhari
THERAPEUTIC USESTHERAPEUTIC USES
ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS
Efek sampingEfek samping
Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital
ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas
IV- insufisiensi ginjal CNS
PENCICLOVIRPENCICLOVIR
Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV
Aktif terhadap HBV (hepatiis B virus)
MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine
kinase Penciclovir trifosfat merupakan inhibitor
kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir
tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi
Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7
hari seara dengan asiklovir utk infeksi mucocutaneous HSV
Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV
Efek sampingEfek samping
Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak
teridentifikasi
DRUG MECHANISMVIRAL
SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Acylovir Metabolized by thymidine kinase to triphosphate
Herpes simplex 1 amp 2 varicella zoster
Produce abnormal thymidine kinase
Skin irritation burning crystalline nephropathy
IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction
Pencyclovir Oral HSV (coldsores)
Topical
Valacyclovir L-valyl ester of acyclovir converted to acyclovir
Herpes zoster (shingles)
Nausea headache PO Slightly better oral absorption than acyclovir
No clear advantage over acyclovir
Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks
Herpes simplex keratitis No effect on RNA viruses
Resistance develops
Photophobia irritation of conjunctiva amp eyelid
Eyedrops Drug is a halogenated derivative of deoxyuridine
Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate
Shortens duration of herpes zoster amp genital herpes
Minimal toxicity Headache
PO Decrease dose with renal dysfunction
Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells
CMV retinitis amp severe systemic CMV infections
Some resistant strains lack thymidine kinase Cannot activate drug
Granulocytopenia thrombocytopenia
IVPO Excreted unchanged in urine Decrease dose with renal dysfunction
Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)
ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
1 2 3
6
5
4
78
bull Banyak virus menginfeksi sel inang spesifik
bull Banyak infeksi virus bersifat self limiting tidak memerlukan pengobatan cth common cold yang disebabkan oleh rinovirus
bull Infeksi virus yang umum seperti influenza chicken pox mumps biasanya dapat diatasi oleh sistem imun tubuh
Virus lain dapat menyebabkan penyakit serius dan fatal sehingga memerlukan pengobatan yang agresif cth HIV (AIDS)
Poin penting
Virus Genera Nucleic Acid Clinical Illness
Adenovirus DNA URTIs Eye infections
Hepadnaviridae DNA Hepatitis B Cancer ()
Herpesvirus DNA Genital herpes Varicella Encephalitis Retinitis
Papillomavirus DNA Papilloma Cancer
Parvovirus DNA Erythema infectiosum
Arenavirus RNA Lymphocytic choriomeningitis
Bunyavirus RNA Encephalitis
Coronavirus RNA URTIs
Influenzavirus RNA Influenza
Paramyxovirus RNA Measles URTIs
Picornavirus RNA Poliomyelitis diarrhea URTIs
Retrovirus RNA Leukemia AIDS
Rhabdovirus RNA Rabies
Togavirus RNA Rubella Yellow fever
Virus Groups of Clinical Importance
Obat anti virusObat anti virus Vaksin sering digunakan untuk membangun
sistem kekebalan sebelum infeksi virus terjadi
Agar efektif antivirus harus dapat menghambat entry atau keluarya virus ke sel inang atau aktif di dalam sel inang
9
Tantangan terapi anti virus replikasi virus yang cepat menyebabkan
sulitnya mengembangkan anti virus yang efektif
Virus dapat bermutasi dengan cepat obat menjadi tidak efektif
Kesulitan obat menemukan virus tanpa mengganggu sel normal inang
10
ANTI-HERPES ANTI VZVANTI-HERPES ANTI VZV
HSV = herpes simplex virusHSV = herpes simplex virusVZV = Varicella Zoster virusVZV = Varicella Zoster virus
ACYCLOVIRACYCLOVIR
Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV
(ebstein bar virus) CMV (cytomegalo virus)
Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi
FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan
dosis BA relatif meningkat sampai 70 setelah
pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk
cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan
plasenta Absorbsi perkutan rendah
Penggunaan dalam terapiPenggunaan dalam terapi
Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg
3xhari
THERAPEUTIC USESTHERAPEUTIC USES
ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS
Efek sampingEfek samping
Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital
ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas
IV- insufisiensi ginjal CNS
PENCICLOVIRPENCICLOVIR
Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV
Aktif terhadap HBV (hepatiis B virus)
MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine
kinase Penciclovir trifosfat merupakan inhibitor
kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir
tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi
Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7
hari seara dengan asiklovir utk infeksi mucocutaneous HSV
Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV
Efek sampingEfek samping
Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak
teridentifikasi
DRUG MECHANISMVIRAL
SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Acylovir Metabolized by thymidine kinase to triphosphate
Herpes simplex 1 amp 2 varicella zoster
Produce abnormal thymidine kinase
Skin irritation burning crystalline nephropathy
IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction
Pencyclovir Oral HSV (coldsores)
Topical
Valacyclovir L-valyl ester of acyclovir converted to acyclovir
Herpes zoster (shingles)
Nausea headache PO Slightly better oral absorption than acyclovir
No clear advantage over acyclovir
Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks
Herpes simplex keratitis No effect on RNA viruses
Resistance develops
Photophobia irritation of conjunctiva amp eyelid
Eyedrops Drug is a halogenated derivative of deoxyuridine
Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate
Shortens duration of herpes zoster amp genital herpes
Minimal toxicity Headache
PO Decrease dose with renal dysfunction
Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells
CMV retinitis amp severe systemic CMV infections
Some resistant strains lack thymidine kinase Cannot activate drug
Granulocytopenia thrombocytopenia
IVPO Excreted unchanged in urine Decrease dose with renal dysfunction
Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)
ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
bull Banyak virus menginfeksi sel inang spesifik
bull Banyak infeksi virus bersifat self limiting tidak memerlukan pengobatan cth common cold yang disebabkan oleh rinovirus
bull Infeksi virus yang umum seperti influenza chicken pox mumps biasanya dapat diatasi oleh sistem imun tubuh
Virus lain dapat menyebabkan penyakit serius dan fatal sehingga memerlukan pengobatan yang agresif cth HIV (AIDS)
Poin penting
Virus Genera Nucleic Acid Clinical Illness
Adenovirus DNA URTIs Eye infections
Hepadnaviridae DNA Hepatitis B Cancer ()
Herpesvirus DNA Genital herpes Varicella Encephalitis Retinitis
Papillomavirus DNA Papilloma Cancer
Parvovirus DNA Erythema infectiosum
Arenavirus RNA Lymphocytic choriomeningitis
Bunyavirus RNA Encephalitis
Coronavirus RNA URTIs
Influenzavirus RNA Influenza
Paramyxovirus RNA Measles URTIs
Picornavirus RNA Poliomyelitis diarrhea URTIs
Retrovirus RNA Leukemia AIDS
Rhabdovirus RNA Rabies
Togavirus RNA Rubella Yellow fever
Virus Groups of Clinical Importance
Obat anti virusObat anti virus Vaksin sering digunakan untuk membangun
sistem kekebalan sebelum infeksi virus terjadi
Agar efektif antivirus harus dapat menghambat entry atau keluarya virus ke sel inang atau aktif di dalam sel inang
9
Tantangan terapi anti virus replikasi virus yang cepat menyebabkan
sulitnya mengembangkan anti virus yang efektif
Virus dapat bermutasi dengan cepat obat menjadi tidak efektif
Kesulitan obat menemukan virus tanpa mengganggu sel normal inang
10
ANTI-HERPES ANTI VZVANTI-HERPES ANTI VZV
HSV = herpes simplex virusHSV = herpes simplex virusVZV = Varicella Zoster virusVZV = Varicella Zoster virus
ACYCLOVIRACYCLOVIR
Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV
(ebstein bar virus) CMV (cytomegalo virus)
Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi
FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan
dosis BA relatif meningkat sampai 70 setelah
pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk
cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan
plasenta Absorbsi perkutan rendah
Penggunaan dalam terapiPenggunaan dalam terapi
Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg
3xhari
THERAPEUTIC USESTHERAPEUTIC USES
ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS
Efek sampingEfek samping
Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital
ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas
IV- insufisiensi ginjal CNS
PENCICLOVIRPENCICLOVIR
Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV
Aktif terhadap HBV (hepatiis B virus)
MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine
kinase Penciclovir trifosfat merupakan inhibitor
kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir
tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi
Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7
hari seara dengan asiklovir utk infeksi mucocutaneous HSV
Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV
Efek sampingEfek samping
Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak
teridentifikasi
DRUG MECHANISMVIRAL
SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Acylovir Metabolized by thymidine kinase to triphosphate
Herpes simplex 1 amp 2 varicella zoster
Produce abnormal thymidine kinase
Skin irritation burning crystalline nephropathy
IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction
Pencyclovir Oral HSV (coldsores)
Topical
Valacyclovir L-valyl ester of acyclovir converted to acyclovir
Herpes zoster (shingles)
Nausea headache PO Slightly better oral absorption than acyclovir
No clear advantage over acyclovir
Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks
Herpes simplex keratitis No effect on RNA viruses
Resistance develops
Photophobia irritation of conjunctiva amp eyelid
Eyedrops Drug is a halogenated derivative of deoxyuridine
Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate
Shortens duration of herpes zoster amp genital herpes
Minimal toxicity Headache
PO Decrease dose with renal dysfunction
Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells
CMV retinitis amp severe systemic CMV infections
Some resistant strains lack thymidine kinase Cannot activate drug
Granulocytopenia thrombocytopenia
IVPO Excreted unchanged in urine Decrease dose with renal dysfunction
Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)
ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
Virus Genera Nucleic Acid Clinical Illness
Adenovirus DNA URTIs Eye infections
Hepadnaviridae DNA Hepatitis B Cancer ()
Herpesvirus DNA Genital herpes Varicella Encephalitis Retinitis
Papillomavirus DNA Papilloma Cancer
Parvovirus DNA Erythema infectiosum
Arenavirus RNA Lymphocytic choriomeningitis
Bunyavirus RNA Encephalitis
Coronavirus RNA URTIs
Influenzavirus RNA Influenza
Paramyxovirus RNA Measles URTIs
Picornavirus RNA Poliomyelitis diarrhea URTIs
Retrovirus RNA Leukemia AIDS
Rhabdovirus RNA Rabies
Togavirus RNA Rubella Yellow fever
Virus Groups of Clinical Importance
Obat anti virusObat anti virus Vaksin sering digunakan untuk membangun
sistem kekebalan sebelum infeksi virus terjadi
Agar efektif antivirus harus dapat menghambat entry atau keluarya virus ke sel inang atau aktif di dalam sel inang
9
Tantangan terapi anti virus replikasi virus yang cepat menyebabkan
sulitnya mengembangkan anti virus yang efektif
Virus dapat bermutasi dengan cepat obat menjadi tidak efektif
Kesulitan obat menemukan virus tanpa mengganggu sel normal inang
10
ANTI-HERPES ANTI VZVANTI-HERPES ANTI VZV
HSV = herpes simplex virusHSV = herpes simplex virusVZV = Varicella Zoster virusVZV = Varicella Zoster virus
ACYCLOVIRACYCLOVIR
Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV
(ebstein bar virus) CMV (cytomegalo virus)
Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi
FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan
dosis BA relatif meningkat sampai 70 setelah
pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk
cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan
plasenta Absorbsi perkutan rendah
Penggunaan dalam terapiPenggunaan dalam terapi
Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg
3xhari
THERAPEUTIC USESTHERAPEUTIC USES
ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS
Efek sampingEfek samping
Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital
ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas
IV- insufisiensi ginjal CNS
PENCICLOVIRPENCICLOVIR
Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV
Aktif terhadap HBV (hepatiis B virus)
MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine
kinase Penciclovir trifosfat merupakan inhibitor
kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir
tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi
Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7
hari seara dengan asiklovir utk infeksi mucocutaneous HSV
Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV
Efek sampingEfek samping
Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak
teridentifikasi
DRUG MECHANISMVIRAL
SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Acylovir Metabolized by thymidine kinase to triphosphate
Herpes simplex 1 amp 2 varicella zoster
Produce abnormal thymidine kinase
Skin irritation burning crystalline nephropathy
IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction
Pencyclovir Oral HSV (coldsores)
Topical
Valacyclovir L-valyl ester of acyclovir converted to acyclovir
Herpes zoster (shingles)
Nausea headache PO Slightly better oral absorption than acyclovir
No clear advantage over acyclovir
Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks
Herpes simplex keratitis No effect on RNA viruses
Resistance develops
Photophobia irritation of conjunctiva amp eyelid
Eyedrops Drug is a halogenated derivative of deoxyuridine
Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate
Shortens duration of herpes zoster amp genital herpes
Minimal toxicity Headache
PO Decrease dose with renal dysfunction
Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells
CMV retinitis amp severe systemic CMV infections
Some resistant strains lack thymidine kinase Cannot activate drug
Granulocytopenia thrombocytopenia
IVPO Excreted unchanged in urine Decrease dose with renal dysfunction
Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)
ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
Obat anti virusObat anti virus Vaksin sering digunakan untuk membangun
sistem kekebalan sebelum infeksi virus terjadi
Agar efektif antivirus harus dapat menghambat entry atau keluarya virus ke sel inang atau aktif di dalam sel inang
9
Tantangan terapi anti virus replikasi virus yang cepat menyebabkan
sulitnya mengembangkan anti virus yang efektif
Virus dapat bermutasi dengan cepat obat menjadi tidak efektif
Kesulitan obat menemukan virus tanpa mengganggu sel normal inang
10
ANTI-HERPES ANTI VZVANTI-HERPES ANTI VZV
HSV = herpes simplex virusHSV = herpes simplex virusVZV = Varicella Zoster virusVZV = Varicella Zoster virus
ACYCLOVIRACYCLOVIR
Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV
(ebstein bar virus) CMV (cytomegalo virus)
Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi
FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan
dosis BA relatif meningkat sampai 70 setelah
pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk
cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan
plasenta Absorbsi perkutan rendah
Penggunaan dalam terapiPenggunaan dalam terapi
Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg
3xhari
THERAPEUTIC USESTHERAPEUTIC USES
ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS
Efek sampingEfek samping
Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital
ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas
IV- insufisiensi ginjal CNS
PENCICLOVIRPENCICLOVIR
Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV
Aktif terhadap HBV (hepatiis B virus)
MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine
kinase Penciclovir trifosfat merupakan inhibitor
kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir
tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi
Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7
hari seara dengan asiklovir utk infeksi mucocutaneous HSV
Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV
Efek sampingEfek samping
Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak
teridentifikasi
DRUG MECHANISMVIRAL
SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Acylovir Metabolized by thymidine kinase to triphosphate
Herpes simplex 1 amp 2 varicella zoster
Produce abnormal thymidine kinase
Skin irritation burning crystalline nephropathy
IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction
Pencyclovir Oral HSV (coldsores)
Topical
Valacyclovir L-valyl ester of acyclovir converted to acyclovir
Herpes zoster (shingles)
Nausea headache PO Slightly better oral absorption than acyclovir
No clear advantage over acyclovir
Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks
Herpes simplex keratitis No effect on RNA viruses
Resistance develops
Photophobia irritation of conjunctiva amp eyelid
Eyedrops Drug is a halogenated derivative of deoxyuridine
Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate
Shortens duration of herpes zoster amp genital herpes
Minimal toxicity Headache
PO Decrease dose with renal dysfunction
Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells
CMV retinitis amp severe systemic CMV infections
Some resistant strains lack thymidine kinase Cannot activate drug
Granulocytopenia thrombocytopenia
IVPO Excreted unchanged in urine Decrease dose with renal dysfunction
Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)
ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
Tantangan terapi anti virus replikasi virus yang cepat menyebabkan
sulitnya mengembangkan anti virus yang efektif
Virus dapat bermutasi dengan cepat obat menjadi tidak efektif
Kesulitan obat menemukan virus tanpa mengganggu sel normal inang
10
ANTI-HERPES ANTI VZVANTI-HERPES ANTI VZV
HSV = herpes simplex virusHSV = herpes simplex virusVZV = Varicella Zoster virusVZV = Varicella Zoster virus
ACYCLOVIRACYCLOVIR
Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV
(ebstein bar virus) CMV (cytomegalo virus)
Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi
FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan
dosis BA relatif meningkat sampai 70 setelah
pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk
cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan
plasenta Absorbsi perkutan rendah
Penggunaan dalam terapiPenggunaan dalam terapi
Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg
3xhari
THERAPEUTIC USESTHERAPEUTIC USES
ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS
Efek sampingEfek samping
Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital
ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas
IV- insufisiensi ginjal CNS
PENCICLOVIRPENCICLOVIR
Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV
Aktif terhadap HBV (hepatiis B virus)
MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine
kinase Penciclovir trifosfat merupakan inhibitor
kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir
tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi
Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7
hari seara dengan asiklovir utk infeksi mucocutaneous HSV
Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV
Efek sampingEfek samping
Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak
teridentifikasi
DRUG MECHANISMVIRAL
SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Acylovir Metabolized by thymidine kinase to triphosphate
Herpes simplex 1 amp 2 varicella zoster
Produce abnormal thymidine kinase
Skin irritation burning crystalline nephropathy
IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction
Pencyclovir Oral HSV (coldsores)
Topical
Valacyclovir L-valyl ester of acyclovir converted to acyclovir
Herpes zoster (shingles)
Nausea headache PO Slightly better oral absorption than acyclovir
No clear advantage over acyclovir
Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks
Herpes simplex keratitis No effect on RNA viruses
Resistance develops
Photophobia irritation of conjunctiva amp eyelid
Eyedrops Drug is a halogenated derivative of deoxyuridine
Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate
Shortens duration of herpes zoster amp genital herpes
Minimal toxicity Headache
PO Decrease dose with renal dysfunction
Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells
CMV retinitis amp severe systemic CMV infections
Some resistant strains lack thymidine kinase Cannot activate drug
Granulocytopenia thrombocytopenia
IVPO Excreted unchanged in urine Decrease dose with renal dysfunction
Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)
ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
ANTI-HERPES ANTI VZVANTI-HERPES ANTI VZV
HSV = herpes simplex virusHSV = herpes simplex virusVZV = Varicella Zoster virusVZV = Varicella Zoster virus
ACYCLOVIRACYCLOVIR
Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV
(ebstein bar virus) CMV (cytomegalo virus)
Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi
FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan
dosis BA relatif meningkat sampai 70 setelah
pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk
cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan
plasenta Absorbsi perkutan rendah
Penggunaan dalam terapiPenggunaan dalam terapi
Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg
3xhari
THERAPEUTIC USESTHERAPEUTIC USES
ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS
Efek sampingEfek samping
Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital
ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas
IV- insufisiensi ginjal CNS
PENCICLOVIRPENCICLOVIR
Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV
Aktif terhadap HBV (hepatiis B virus)
MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine
kinase Penciclovir trifosfat merupakan inhibitor
kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir
tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi
Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7
hari seara dengan asiklovir utk infeksi mucocutaneous HSV
Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV
Efek sampingEfek samping
Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak
teridentifikasi
DRUG MECHANISMVIRAL
SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Acylovir Metabolized by thymidine kinase to triphosphate
Herpes simplex 1 amp 2 varicella zoster
Produce abnormal thymidine kinase
Skin irritation burning crystalline nephropathy
IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction
Pencyclovir Oral HSV (coldsores)
Topical
Valacyclovir L-valyl ester of acyclovir converted to acyclovir
Herpes zoster (shingles)
Nausea headache PO Slightly better oral absorption than acyclovir
No clear advantage over acyclovir
Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks
Herpes simplex keratitis No effect on RNA viruses
Resistance develops
Photophobia irritation of conjunctiva amp eyelid
Eyedrops Drug is a halogenated derivative of deoxyuridine
Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate
Shortens duration of herpes zoster amp genital herpes
Minimal toxicity Headache
PO Decrease dose with renal dysfunction
Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells
CMV retinitis amp severe systemic CMV infections
Some resistant strains lack thymidine kinase Cannot activate drug
Granulocytopenia thrombocytopenia
IVPO Excreted unchanged in urine Decrease dose with renal dysfunction
Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)
ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
ACYCLOVIRACYCLOVIR
Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV
(ebstein bar virus) CMV (cytomegalo virus)
Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi
FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan
dosis BA relatif meningkat sampai 70 setelah
pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk
cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan
plasenta Absorbsi perkutan rendah
Penggunaan dalam terapiPenggunaan dalam terapi
Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg
3xhari
THERAPEUTIC USESTHERAPEUTIC USES
ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS
Efek sampingEfek samping
Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital
ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas
IV- insufisiensi ginjal CNS
PENCICLOVIRPENCICLOVIR
Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV
Aktif terhadap HBV (hepatiis B virus)
MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine
kinase Penciclovir trifosfat merupakan inhibitor
kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir
tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi
Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7
hari seara dengan asiklovir utk infeksi mucocutaneous HSV
Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV
Efek sampingEfek samping
Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak
teridentifikasi
DRUG MECHANISMVIRAL
SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Acylovir Metabolized by thymidine kinase to triphosphate
Herpes simplex 1 amp 2 varicella zoster
Produce abnormal thymidine kinase
Skin irritation burning crystalline nephropathy
IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction
Pencyclovir Oral HSV (coldsores)
Topical
Valacyclovir L-valyl ester of acyclovir converted to acyclovir
Herpes zoster (shingles)
Nausea headache PO Slightly better oral absorption than acyclovir
No clear advantage over acyclovir
Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks
Herpes simplex keratitis No effect on RNA viruses
Resistance develops
Photophobia irritation of conjunctiva amp eyelid
Eyedrops Drug is a halogenated derivative of deoxyuridine
Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate
Shortens duration of herpes zoster amp genital herpes
Minimal toxicity Headache
PO Decrease dose with renal dysfunction
Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells
CMV retinitis amp severe systemic CMV infections
Some resistant strains lack thymidine kinase Cannot activate drug
Granulocytopenia thrombocytopenia
IVPO Excreted unchanged in urine Decrease dose with renal dysfunction
Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)
ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi
FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan
dosis BA relatif meningkat sampai 70 setelah
pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk
cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan
plasenta Absorbsi perkutan rendah
Penggunaan dalam terapiPenggunaan dalam terapi
Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg
3xhari
THERAPEUTIC USESTHERAPEUTIC USES
ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS
Efek sampingEfek samping
Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital
ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas
IV- insufisiensi ginjal CNS
PENCICLOVIRPENCICLOVIR
Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV
Aktif terhadap HBV (hepatiis B virus)
MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine
kinase Penciclovir trifosfat merupakan inhibitor
kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir
tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi
Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7
hari seara dengan asiklovir utk infeksi mucocutaneous HSV
Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV
Efek sampingEfek samping
Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak
teridentifikasi
DRUG MECHANISMVIRAL
SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Acylovir Metabolized by thymidine kinase to triphosphate
Herpes simplex 1 amp 2 varicella zoster
Produce abnormal thymidine kinase
Skin irritation burning crystalline nephropathy
IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction
Pencyclovir Oral HSV (coldsores)
Topical
Valacyclovir L-valyl ester of acyclovir converted to acyclovir
Herpes zoster (shingles)
Nausea headache PO Slightly better oral absorption than acyclovir
No clear advantage over acyclovir
Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks
Herpes simplex keratitis No effect on RNA viruses
Resistance develops
Photophobia irritation of conjunctiva amp eyelid
Eyedrops Drug is a halogenated derivative of deoxyuridine
Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate
Shortens duration of herpes zoster amp genital herpes
Minimal toxicity Headache
PO Decrease dose with renal dysfunction
Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells
CMV retinitis amp severe systemic CMV infections
Some resistant strains lack thymidine kinase Cannot activate drug
Granulocytopenia thrombocytopenia
IVPO Excreted unchanged in urine Decrease dose with renal dysfunction
Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)
ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan
dosis BA relatif meningkat sampai 70 setelah
pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk
cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan
plasenta Absorbsi perkutan rendah
Penggunaan dalam terapiPenggunaan dalam terapi
Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg
3xhari
THERAPEUTIC USESTHERAPEUTIC USES
ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS
Efek sampingEfek samping
Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital
ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas
IV- insufisiensi ginjal CNS
PENCICLOVIRPENCICLOVIR
Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV
Aktif terhadap HBV (hepatiis B virus)
MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine
kinase Penciclovir trifosfat merupakan inhibitor
kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir
tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi
Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7
hari seara dengan asiklovir utk infeksi mucocutaneous HSV
Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV
Efek sampingEfek samping
Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak
teridentifikasi
DRUG MECHANISMVIRAL
SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Acylovir Metabolized by thymidine kinase to triphosphate
Herpes simplex 1 amp 2 varicella zoster
Produce abnormal thymidine kinase
Skin irritation burning crystalline nephropathy
IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction
Pencyclovir Oral HSV (coldsores)
Topical
Valacyclovir L-valyl ester of acyclovir converted to acyclovir
Herpes zoster (shingles)
Nausea headache PO Slightly better oral absorption than acyclovir
No clear advantage over acyclovir
Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks
Herpes simplex keratitis No effect on RNA viruses
Resistance develops
Photophobia irritation of conjunctiva amp eyelid
Eyedrops Drug is a halogenated derivative of deoxyuridine
Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate
Shortens duration of herpes zoster amp genital herpes
Minimal toxicity Headache
PO Decrease dose with renal dysfunction
Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells
CMV retinitis amp severe systemic CMV infections
Some resistant strains lack thymidine kinase Cannot activate drug
Granulocytopenia thrombocytopenia
IVPO Excreted unchanged in urine Decrease dose with renal dysfunction
Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)
ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
Penggunaan dalam terapiPenggunaan dalam terapi
Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg
3xhari
THERAPEUTIC USESTHERAPEUTIC USES
ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS
Efek sampingEfek samping
Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital
ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas
IV- insufisiensi ginjal CNS
PENCICLOVIRPENCICLOVIR
Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV
Aktif terhadap HBV (hepatiis B virus)
MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine
kinase Penciclovir trifosfat merupakan inhibitor
kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir
tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi
Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7
hari seara dengan asiklovir utk infeksi mucocutaneous HSV
Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV
Efek sampingEfek samping
Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak
teridentifikasi
DRUG MECHANISMVIRAL
SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Acylovir Metabolized by thymidine kinase to triphosphate
Herpes simplex 1 amp 2 varicella zoster
Produce abnormal thymidine kinase
Skin irritation burning crystalline nephropathy
IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction
Pencyclovir Oral HSV (coldsores)
Topical
Valacyclovir L-valyl ester of acyclovir converted to acyclovir
Herpes zoster (shingles)
Nausea headache PO Slightly better oral absorption than acyclovir
No clear advantage over acyclovir
Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks
Herpes simplex keratitis No effect on RNA viruses
Resistance develops
Photophobia irritation of conjunctiva amp eyelid
Eyedrops Drug is a halogenated derivative of deoxyuridine
Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate
Shortens duration of herpes zoster amp genital herpes
Minimal toxicity Headache
PO Decrease dose with renal dysfunction
Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells
CMV retinitis amp severe systemic CMV infections
Some resistant strains lack thymidine kinase Cannot activate drug
Granulocytopenia thrombocytopenia
IVPO Excreted unchanged in urine Decrease dose with renal dysfunction
Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)
ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
THERAPEUTIC USESTHERAPEUTIC USES
ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS
Efek sampingEfek samping
Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital
ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas
IV- insufisiensi ginjal CNS
PENCICLOVIRPENCICLOVIR
Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV
Aktif terhadap HBV (hepatiis B virus)
MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine
kinase Penciclovir trifosfat merupakan inhibitor
kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir
tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi
Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7
hari seara dengan asiklovir utk infeksi mucocutaneous HSV
Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV
Efek sampingEfek samping
Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak
teridentifikasi
DRUG MECHANISMVIRAL
SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Acylovir Metabolized by thymidine kinase to triphosphate
Herpes simplex 1 amp 2 varicella zoster
Produce abnormal thymidine kinase
Skin irritation burning crystalline nephropathy
IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction
Pencyclovir Oral HSV (coldsores)
Topical
Valacyclovir L-valyl ester of acyclovir converted to acyclovir
Herpes zoster (shingles)
Nausea headache PO Slightly better oral absorption than acyclovir
No clear advantage over acyclovir
Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks
Herpes simplex keratitis No effect on RNA viruses
Resistance develops
Photophobia irritation of conjunctiva amp eyelid
Eyedrops Drug is a halogenated derivative of deoxyuridine
Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate
Shortens duration of herpes zoster amp genital herpes
Minimal toxicity Headache
PO Decrease dose with renal dysfunction
Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells
CMV retinitis amp severe systemic CMV infections
Some resistant strains lack thymidine kinase Cannot activate drug
Granulocytopenia thrombocytopenia
IVPO Excreted unchanged in urine Decrease dose with renal dysfunction
Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)
ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
Efek sampingEfek samping
Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital
ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas
IV- insufisiensi ginjal CNS
PENCICLOVIRPENCICLOVIR
Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV
Aktif terhadap HBV (hepatiis B virus)
MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine
kinase Penciclovir trifosfat merupakan inhibitor
kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir
tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi
Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7
hari seara dengan asiklovir utk infeksi mucocutaneous HSV
Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV
Efek sampingEfek samping
Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak
teridentifikasi
DRUG MECHANISMVIRAL
SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Acylovir Metabolized by thymidine kinase to triphosphate
Herpes simplex 1 amp 2 varicella zoster
Produce abnormal thymidine kinase
Skin irritation burning crystalline nephropathy
IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction
Pencyclovir Oral HSV (coldsores)
Topical
Valacyclovir L-valyl ester of acyclovir converted to acyclovir
Herpes zoster (shingles)
Nausea headache PO Slightly better oral absorption than acyclovir
No clear advantage over acyclovir
Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks
Herpes simplex keratitis No effect on RNA viruses
Resistance develops
Photophobia irritation of conjunctiva amp eyelid
Eyedrops Drug is a halogenated derivative of deoxyuridine
Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate
Shortens duration of herpes zoster amp genital herpes
Minimal toxicity Headache
PO Decrease dose with renal dysfunction
Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells
CMV retinitis amp severe systemic CMV infections
Some resistant strains lack thymidine kinase Cannot activate drug
Granulocytopenia thrombocytopenia
IVPO Excreted unchanged in urine Decrease dose with renal dysfunction
Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)
ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
PENCICLOVIRPENCICLOVIR
Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV
Aktif terhadap HBV (hepatiis B virus)
MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine
kinase Penciclovir trifosfat merupakan inhibitor
kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir
tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi
Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7
hari seara dengan asiklovir utk infeksi mucocutaneous HSV
Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV
Efek sampingEfek samping
Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak
teridentifikasi
DRUG MECHANISMVIRAL
SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Acylovir Metabolized by thymidine kinase to triphosphate
Herpes simplex 1 amp 2 varicella zoster
Produce abnormal thymidine kinase
Skin irritation burning crystalline nephropathy
IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction
Pencyclovir Oral HSV (coldsores)
Topical
Valacyclovir L-valyl ester of acyclovir converted to acyclovir
Herpes zoster (shingles)
Nausea headache PO Slightly better oral absorption than acyclovir
No clear advantage over acyclovir
Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks
Herpes simplex keratitis No effect on RNA viruses
Resistance develops
Photophobia irritation of conjunctiva amp eyelid
Eyedrops Drug is a halogenated derivative of deoxyuridine
Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate
Shortens duration of herpes zoster amp genital herpes
Minimal toxicity Headache
PO Decrease dose with renal dysfunction
Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells
CMV retinitis amp severe systemic CMV infections
Some resistant strains lack thymidine kinase Cannot activate drug
Granulocytopenia thrombocytopenia
IVPO Excreted unchanged in urine Decrease dose with renal dysfunction
Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)
ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine
kinase Penciclovir trifosfat merupakan inhibitor
kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir
tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi
Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7
hari seara dengan asiklovir utk infeksi mucocutaneous HSV
Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV
Efek sampingEfek samping
Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak
teridentifikasi
DRUG MECHANISMVIRAL
SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Acylovir Metabolized by thymidine kinase to triphosphate
Herpes simplex 1 amp 2 varicella zoster
Produce abnormal thymidine kinase
Skin irritation burning crystalline nephropathy
IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction
Pencyclovir Oral HSV (coldsores)
Topical
Valacyclovir L-valyl ester of acyclovir converted to acyclovir
Herpes zoster (shingles)
Nausea headache PO Slightly better oral absorption than acyclovir
No clear advantage over acyclovir
Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks
Herpes simplex keratitis No effect on RNA viruses
Resistance develops
Photophobia irritation of conjunctiva amp eyelid
Eyedrops Drug is a halogenated derivative of deoxyuridine
Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate
Shortens duration of herpes zoster amp genital herpes
Minimal toxicity Headache
PO Decrease dose with renal dysfunction
Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells
CMV retinitis amp severe systemic CMV infections
Some resistant strains lack thymidine kinase Cannot activate drug
Granulocytopenia thrombocytopenia
IVPO Excreted unchanged in urine Decrease dose with renal dysfunction
Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)
ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7
hari seara dengan asiklovir utk infeksi mucocutaneous HSV
Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV
Efek sampingEfek samping
Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak
teridentifikasi
DRUG MECHANISMVIRAL
SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Acylovir Metabolized by thymidine kinase to triphosphate
Herpes simplex 1 amp 2 varicella zoster
Produce abnormal thymidine kinase
Skin irritation burning crystalline nephropathy
IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction
Pencyclovir Oral HSV (coldsores)
Topical
Valacyclovir L-valyl ester of acyclovir converted to acyclovir
Herpes zoster (shingles)
Nausea headache PO Slightly better oral absorption than acyclovir
No clear advantage over acyclovir
Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks
Herpes simplex keratitis No effect on RNA viruses
Resistance develops
Photophobia irritation of conjunctiva amp eyelid
Eyedrops Drug is a halogenated derivative of deoxyuridine
Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate
Shortens duration of herpes zoster amp genital herpes
Minimal toxicity Headache
PO Decrease dose with renal dysfunction
Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells
CMV retinitis amp severe systemic CMV infections
Some resistant strains lack thymidine kinase Cannot activate drug
Granulocytopenia thrombocytopenia
IVPO Excreted unchanged in urine Decrease dose with renal dysfunction
Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)
ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
Efek sampingEfek samping
Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak
teridentifikasi
DRUG MECHANISMVIRAL
SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Acylovir Metabolized by thymidine kinase to triphosphate
Herpes simplex 1 amp 2 varicella zoster
Produce abnormal thymidine kinase
Skin irritation burning crystalline nephropathy
IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction
Pencyclovir Oral HSV (coldsores)
Topical
Valacyclovir L-valyl ester of acyclovir converted to acyclovir
Herpes zoster (shingles)
Nausea headache PO Slightly better oral absorption than acyclovir
No clear advantage over acyclovir
Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks
Herpes simplex keratitis No effect on RNA viruses
Resistance develops
Photophobia irritation of conjunctiva amp eyelid
Eyedrops Drug is a halogenated derivative of deoxyuridine
Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate
Shortens duration of herpes zoster amp genital herpes
Minimal toxicity Headache
PO Decrease dose with renal dysfunction
Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells
CMV retinitis amp severe systemic CMV infections
Some resistant strains lack thymidine kinase Cannot activate drug
Granulocytopenia thrombocytopenia
IVPO Excreted unchanged in urine Decrease dose with renal dysfunction
Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)
ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
DRUG MECHANISMVIRAL
SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Acylovir Metabolized by thymidine kinase to triphosphate
Herpes simplex 1 amp 2 varicella zoster
Produce abnormal thymidine kinase
Skin irritation burning crystalline nephropathy
IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction
Pencyclovir Oral HSV (coldsores)
Topical
Valacyclovir L-valyl ester of acyclovir converted to acyclovir
Herpes zoster (shingles)
Nausea headache PO Slightly better oral absorption than acyclovir
No clear advantage over acyclovir
Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks
Herpes simplex keratitis No effect on RNA viruses
Resistance develops
Photophobia irritation of conjunctiva amp eyelid
Eyedrops Drug is a halogenated derivative of deoxyuridine
Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate
Shortens duration of herpes zoster amp genital herpes
Minimal toxicity Headache
PO Decrease dose with renal dysfunction
Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells
CMV retinitis amp severe systemic CMV infections
Some resistant strains lack thymidine kinase Cannot activate drug
Granulocytopenia thrombocytopenia
IVPO Excreted unchanged in urine Decrease dose with renal dysfunction
Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)
ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir
CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia
Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase
CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains
Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea
IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction
Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney
Amantadine Prevents virus from entering susceptible cells
Treatment amp prophylaxis of influenza A
Depression CNS toxicity CHF orthostatic hypotension urinary retention
PO Excreted unmetabolized
Rimantadine Analog of amantadine inhibits viral uncoating
Prophylaxis in children
Fewer CNS side effects risk of seizure
PO Prolonged elimination w renal or hepatic dysfunction
Ribavirin Unknown mechanism
RSV Decreased pulmonary function
Aerosol administration Absorbed systemically
May precipitate in ventilator tubing
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
ANTI-INFLUENZAANTI-INFLUENZA
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA
influenza A di dalam cell inang mencegah replikasi
Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
FKFK
Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme
di urinAmantadin dapat diekskresikan lewat ASI
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
Efek sampingEfek samping
Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)
Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
Penggunaan terapiPenggunaan terapi
Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis
(pengobatan)Pencegahan harus dimulai ketika mulai
teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
FKFK
Diserap dengan cepat setelah pemberian oral (BA 80)
Eliminasi di ginjal dalam bentuk tak berubah
Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
Efek sampingEfek samping
Mual rasa tak nyaman di lambung muntah lokal iritasi
Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
ANTI-HEPATITISANTI-HEPATITIS
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV
DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing
diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan
oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas
imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS
NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine
NNRTIbull Efavirenz bull Etravirine bull Nevirapine
PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull
Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
DRUG MECHANISM amp VIRAL SELECTIVITY
CLINICAL USE
VIRAL RESISTANCE
UNDESIRABLE SIDE EFFECTS
PHARMACOKINETICS
NOTES
Zidovudine (AZT)
Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain
HIV Prevention of maternal-fetal transmission of HIV
Mutations in reverse transcriptase
Headaches nausea myalgias anemia neutropenia macrocytosis
PO Well absorbed rapidly metabolized by liver
Acetaminophen increases risk of hematologic toxicity
Didanosine (ddl)Zalcitabine (ddC)Lamivudine
-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group
HIV Mutations in reverse transcriptase
Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain
IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction
Limited utility as a single agent therapy because of viral resistance
Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation
HIV Peripheral neuropathy
PO Not indicated for initial monotherapy of HIV
ANTIVIRAL DRUGS - RETROVIRUSES
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial
RitonavirIndinavirSaquinavirNelfinavir
Inhibts HIV protease Results in immature virion
HIV Mutations in protease sequence reduce affinity of protease inhibitors
GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones
PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration
Potentially serious drug interactions due to P450 competition
NevirapineDelavirdene
Nob-nucleoside inhibitor of HIV reverse transcriptase
HIV Never as monotherapy due to rapid development of resistance
Rapid resistance develops due to mutations in reverse transcriptase
Severe skin rash fever nausea headache
PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene
Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial