Antiviral Rubella Picorna 2011

8/3/2019 Antiviral Rubella Picorna 2011

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ANTIVIRALS

Mary Joyce Saborrido- Teoxon, RMT, MD

FEU-NRMF Institute of Medicine



What to expect?

• To review the viral replication.

• To site the effects of each antiviral drugs.

• To enumerate the different antiviral drugs.

• To identify the uses of each antiviral drugs.

• To discuss the different adverse effect of

each to human.



Steps inViral

Replication

Adsorption. The virus attaches to the host

cell to specific binding of its spikes to cell

receptors.

1

Penetration. The virus is engulfed into a

vesicle and its envelope is

Uncoated, thereby freeing the viral RNA

into the cell cytoplasm.

2

3

Synthesis. Replication

and Protein Production.

Under the control of viral

genes, the cell synthesizes

the basic components of

new viruses: RNAmolecules, capsomers,

spikes.

4

Released. Enveloped viruses bud off of the

membrane, carrying away an envelope with

the spikes. This complete virus or virion isready to infect another cell.

6

5

Assembly. Viral spike proteins are insertedinto the cell membrane for the viral envelope;

nucleocapsid is formed from RNA and

capsomers.

5



Viral penetrationinhibitors

• Amantadine

• Rimantadine



Amantadine & Rimantadine

• MOA: (-) attachment, penetration & uncoating of Influenza A virus

• Use: PROPHYLAXIS only (but can duration of symptoms by 1-2 days)

• Form: PO

• AE: CNS effects (nervousness, insomnia,hallucination, seizure in OD)

• Resistance: Documented



Viral nucleic acid

synthesis inhibitors

• Antiherpetics

•

Antimyxovirus• Antiretrovirals



Acyclovir- MOA

AcyclovirThymidine

Kinase

Acyclovir

monophosphateThymidine

Kinase

DNA Polymerase

(DNA chain termination)

Acyclovir

triphosphate



Acyclovir- HSV & VZV

ViralShedding

Primary

Infection

andRecurrence


http://slidepdf.com/reader/full/antiviral-rubella-picorna-2011 9/39Acyclovir- HSV & VZV



Acyclovir

• Propyhlactic in immunocompromised

• Form: Topical, Oral, IV

• AE: IV (Crystalluria & Neurotoxic)

•

Resistance: due to changes in DNApolymerase

: activity of TK



Famciclovir &

Valacyclovir

•MOA: same as Acyclovir

• Activity against strains

resistant to acyclovir, but notTK - strains



Ganciclovir

• MOA: same as Acyclovir (not DNA chain

termination)

• Resistance: same as Acyclovir

• Use: HSV, VZV, CMV (prophylaxis & Tx)

• Form: Oral, IV and retinal implant

• AE: Dose-limiting hematotoxicity ( WBC,plt),

mucositis, fever, rash, crystalluria, Seizures in

OD



Foscarnet

• MOA: Not an antimetabolite, but still (-) viral

DNA & RNA polymerases

• USE: identical to Ganciclovir, but > activity versus

acyclovir-resistant strains of HSV

• Form: IV

• AE: Dose-limiting nephrotoxicity w/ ATN,

electroltre imbalance Ca+2 tremors and

seizures.



Viral nucleic acid

synthesis inhibitors

Anti-myxovirus drugs



Ribavirin

• MOA: Ribavirin monophosphate IMPdehydrogenase

Ribavirin triphosphate viral RNApolymerase and end-capping of viral RNA

• Form: Aerosol, Topical

• Use: RSV, Infleunza A & B, Lassa fever,

Hantavirus, adjuncts to alpha-interferons inHepa C

• AE: Hematotoxic, Upper airway irritation,Teratogenic



Reverse TranscriptaseInhibitors (RTIs)

Anti-retrovirus drugs



Nucleoside RTIs (NRTIs)

•Components of most combination drugregimens used in HIV infection

• Used 2 NRTIs w/ PI

• Use in HAART ( viral RNA, CD4 cells,opportunistic infxn)



Nonnucleoside RTIs

• Resistance emerges if used

individually

• Additive/ Synergistic agaisnt HIV



Zidovudine (Azidothymidine, ZDV, AZT)

• MOA: Zidovudine triphosphate RT (Viral chain

termination)

• Form: Oral

• AE: Dose-limiting hematotoxicity ( PMN, RBC,

Plt) may require bld transfusion, HA, Asthenia,

myalgia, myopathy, peripheral neuropathy, lacticacidosis

• Resistance: Mutation in the gene that codes RT



Other NRTIs

• MOA: Same as AZT

• Resistance: same as AZT

• AE: Different



Didanosine,DDI

Pancreatitis (major, dose-limiting) – peripheral

neuropathy, hyperuricemia, liverdysfxn

Zalcitabine,DDC

Peripheral neuropathy (major,dose-limiting) – GI distress,pancreatitis, neutropenia, rash

Stavudine,D4T

Peripheral neuropathy (major,dose-limiting) –

myelosuppresion < ZDVLamivudine,3TC

Least toxic of NRTIs, but someGI effects and neutropenia



ProteaseInhibitors (PIs)

Anti-retrovirus drugs



PIs

• MOA: Aspartate protease is a viral enzyme thatcleaves precursor polypeptides in HIV buds toform the proteins of the mature virus core.

• Use: In combination w/ 2 NRTIs

• AE: Indinavir (Nephrolithiasis, GI distress, plt, (-P450)

Ritonavir (GI distress, asthenia, Paresthesia,

(-) P450)Saquinavir (one of the least toxic, has very

low oral bioavailability)



Viral

neuramidase

inhibitors



Zanamivir & Oseltamivir

• MOA: (-) neuramidase of Influenza A

& B, enzymes that prevent clumpingof virions

• Use: PROPHYLAXIS, duration of flu

symptoms by 2-3 days• AE: N & V, Zanamivir (Nasal & Throat

irritation)



MOA Major Drugs

Block viralpenetration/ uncoating Amantadine,Rimantadine

Inhibit viral DNApolymerase

Acyclovir, Foscarnet,Ganciclovir

Inhibit viral RNApolymerase

Foscarnet, Ribavirin

Inhibit viral reverse

transcriptase

AZT, DDI, DDC, D4T,

3TCInhibit viral asapartateprotease

Indinavir, Ritonavir,Saquinavir

Inhibit viralneuramidase

Zanamivir, Oseltamivir



Case # 1

• A 25-year-old woman had

arthralgia and mild rash on herface and spread to her body. She

recalled that she had felt as if she

had flu a few days before theonset of the rash. The rash

disappeared in 4 days.





•

What is the probable causative agent?• A 25-year-old woman had arthralgia

and mild rash (FACE BODY)

• (+) FLU symptoms few days beforerash

• Rash disappead on the 4th day



• What is the probable causative agent?

• VIRAL EXANTHEM?

• Rubeola ?• Rubella ?

• Roseola ?



RUBEOLA RUBELLA ROSEOLA

Measles

Hard Measles

Red Measles

German Measles

Three day Measles

Exanthem

subitum

Infants adults Infants Adults Infants

FEVER RASH

• 3Cs

• COUGH

• COLDS

CONJUNCTIVITIS• Koplik’s spots

• COMPLICATION

FEVER RASH

• Lymphadenopathy

• Arthralgia

FEVER RASH



• Describe the causative agent as to:

• Structure

• Site of replication

• What features of the case pointed to

the diagnosis of rubella infection?

• How was the infection transmitted?



• What precaution could the patient

have taken to prevent this infection?



MMR Vaccine

•Measles: Schwartz/ Moratensubstrains of Edmonston B strain

• Mumps: Jeryl Lynn strain

• Rubella: RA/ 27-3 strain



PICORNAVIRIDAE

• Small ss(+) RNA viruses

• Naked



Enteroviruses (group)

• Summer-fall peak incidence

• Fecal-oral transmission but do not cause diarrhea

• Peak age group <9 years for most

• Stable at pH3

• Resistant to alcohol, detergents because there is no

envelope

• Polio - ECHO - Entero

• Coxsackie A & B - Hepa A



Polio virus

• Most infections are asymptomatic, small %cause fever (viremia).

• Smaller % cause aseptic meningitis• Poliomyelitis (paralysis) (even smaller%)

results from viral damage to anterior hornmotor neurons

• Vaccines: both are trivalent

-Salk (killed/injectable)

- Sabin (live/oral/ best gut immunity)





Coxsackie A

• Herpangina (vesicles on soft palate and

fauces)• Hand-foot-and mouth disease (oral

lesions primarily in the anterior buccalmucosa)

• Aseptic meningitis

• Acute lymphoglandular pharyngitis

• Common cold

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Antiviral Rubella Picorna 2011