Chemotherapy V

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    Chemotherapy V

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    Fluoroquinolones (FQ)

    Quinolone antimicrobials having one or more

    fluorine substitutions

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    Classification

    I generation FQ

    Norfloxacin

    Ciprofloxacin

    Ofloxacin

    Pefloxacin

    II generation FQ

    Lomefloxacin

    Levofloxacin

    Sparfloxacin

    Gatifloxacin

    Moxifloxacin

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    Pcokinetics of FQs

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    Therapeutic applications of FQs

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    Uses of FQS

    Gonorrhoea

    Chancroid

    Bacterial gastroenteritis caused by Shigella,

    Salmonella and Campy. Jejuni Typhoid

    Bone & soft tissue infection

    Tuberculosis

    Gram (-) septecemia Meningitis

    Conjunctivitis

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    Adverse effects

    Headache

    Dizziness

    Nephrotoxicity

    Diarrhea

    Nausea

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    Drug interactions

    Plasma concentration oftheophylline, caffine

    and warfarin are increased by ciprofloxacin

    NSAIDS may enhance the CNS toxicity of FQs

    seizures are reported

    Antacids may decrease the absorption of FQS

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    Anti tubercular drugs

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    Tuberculosis

    Mycobacteria are slender, rod-shaped bacteriawith lipid-rich cell walls

    that stain poorly with the Gram stain,

    but once stained, the walls cannot be easilydecolorized by treatment with acidified organicsolvents.

    Hence, they are termed acid-fast.

    The most widely encountered mycobacterialinfection is tuberculosis

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    Anti TB drugs

    I line drugs

    Isoniazid (H)

    Rifampin (R)

    Pyrazinamide(Z) Ethambutol (E)

    Streptomycin (S)

    II line drugs

    Cycloserine

    Kanamycin

    Amikacin Capreomycin

    Ethionamide

    PAS

    Ciprofloxacin Clarithromycin

    Azithromycin

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    Isoniazid

    antibacterial activity ofisoniazid is limited to

    mycobacteria.

    readily absorbed from the gastrointestinal

    tract and is widely distributed throughout the

    tissues and body fluids, including the CSF

    Metabolism largely involves acetylation

    excreted in the urine partly as unchanged drug

    and partly in the acetylated form

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    Rifampin

    one of the most active antituberculosis agents

    also effective against most Gram-positive

    bacteria as well as many Gram-negative

    species

    Rifampicin is given orally and is widely

    distributed in the tissues and body fluids

    excreted partly in the urine and partly in the

    bile

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    Rifampin

    Induced hepatic microsomal enzyme which

    increase the degradation of self as wells as

    many other drugs like warfarin,

    glucocorticoids, narcotic analgesics, oral

    antidiabetic drugs, dapsone and oestrogen

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    Ethambutol

    Ethambutol has no effect on organisms other

    than mycobacteria

    Ethambutol is given orally and is well

    absorbed

    it is taken up by erythrocytes and slowly

    released

    partly metabolized and is excreted in the urine

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    Pyrizinamide

    Pyrazinamide is inactive at neutral pH but

    tuberculostatic at acid pH

    well absorbed after oral administration and is

    widely distributed penetrating well into the

    meninges

    excreted through the kidney, mainly by

    glomerular filtration

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    Streptomycin

    First clinically useful drug against TB

    Administered as i.m. inj., distributed only

    extracellularly

    Not metabolized and excreted unchanged in

    urine via glomerular filtration

    May cause ototoxicity, nephrotoxicity and pain

    at injection site

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    Adverse effects I line anti TB drugs

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    Capreomycin

    Peptide antibiotic given by intramuscular

    injection

    May cause kidney damage and injury to the

    eighth nerve, with consequent deafness and

    ataxia

    Should not be given at the same time as

    streptomycin

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    Cycloserine

    Broad-spectrum antibiotic that inhibits the

    growth of many bacteria, including coliforms

    and mycobacteria

    Rapidly absorbed orally, distributed

    throughout the tissues and body fluids, and

    reaches CSF

    Mostly eliminated in active form in the urine

    Adverse effects: headache and irritability to

    depression, convulsions and psychotic states

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    Therapy of TB: DOTS

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    Drugs used to treat leprosy

    Paucibacillary leprosy

    Characterised by one to five numb patches

    is mainly tuberculoid type

    Treated for 6 months with dapsone and rifampicin

    Multibacillaryleprosy

    Characterised by more than five numb skin

    patches

    is mainly lepromatous type

    and is treated for at least 2 years with rifampicin,

    dapsone and clofazimine

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    Dapsone

    Dapsone is chemically related to the

    sulfonamides

    Dapsone is absorbed orally and widely

    distributed

    There is enterohepatic recycling of the drug,

    but some is acetylated and excreted in the

    urine

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    Dapsone

    May cause haemolysis of red cells

    methaemoglobinaemia, anorexia, nausea and

    vomiting, fever, allergic dermatitis and

    neuropathy

    May also cause lepra reactions

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    Clofazimine

    Clofazimine is a dye of complex structure

    has anti-inflammatory activity and is useful in

    patients in whom dapson causes

    inflammatory side effects

    Skin and urine can develop a reddish colour

    and the lesions a blue-black discoloration

    Nausea, giddiness, headache and

    gastrointestinal disturbances

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    Anti malarial drugs

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    Introduction

    Malaria is an acute infectious disease caused

    by four species of the protozoal genus

    Plasmodium

    P. falciparum, P. vivax, P. malariae & P. ovale

    Parasite is transmitted to humans through the

    bite of a female Anopheles mosquito

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    Chloroquine

    Well absorbed orally

    High affinity for melanin, nuclear chromatin &

    retina

    Partly metabolized by liver and slowly

    excreted in urine

    Side effects: nausea, vomiting, anorexia,

    itching, epigastric pain, difficulty in

    accommodation and headache

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    Chloroquine

    Parenteral administration can cause

    hypotension, cardiac depression, arrhythmias

    and CNS toxicity

    Prolonged use may cause loss of vision

    Loss of hearing, rashes photoallergy, mental

    disturbance and graying of hair

    Should not be co administered with other

    antiarrhythmics (mefloquine, amiodarone,

    etc)

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    Mefloquine

    Developed to deal chloroquine resistant P.

    falciparum

    Oral absorption is slow, high plasma protein

    binding

    Extensive metabolism in liver and primarily

    secreted in bile

    Adverse effects: dizziness, nausea, vomiting,

    diarrhoea, abdominal pain and sinus

    bradycardia

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    Mefloquine

    Neuropsychiatric reactions (disturbed sense of

    balance, ataxia, errors in operating machinery,

    strange dreams, anxiety, hellucination and

    rarely convulsions)

    Rarely, Hematological, hepatic and cutaneous

    toxicity

    Interactions: Halofantrine or quinidine can

    cause QTc lengthening or cardiac arrests

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    Quinine

    Levo rotatory alkaloid from cinchona bark

    Rapidly & completely absorbed orally

    Large fraction is metabolized in liver and

    excreted in urine

    Adverse effects: Cinchonism (ringing in ears,

    nausea, vomiting, headache, mental

    confusion, vertigo, difficulty in hearing and

    visual defects)

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    Pyrimethamine

    Slow absorption & concentrated in organs like

    liver, spleen, kidney & lungs

    Metabolized & excreted in urine

    Adverse effects: Nausea, rashes,

    megaloblastic anemia and granulocytopenia

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    Primaquine

    Readily absorbed after oral ingestion

    Oxidized in liver & excreted in urine

    Adverse effects: Haemolysis,

    methemoglobinemia, tachypnoea & cyanosis

    Should be avoided during pregnancy because

    fetus is G-6-PD deficient

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    Artemisinin derivatives

    Artesunate and arteether

    Adverse effects: nausea, vomiting, abdominal

    pain, itching & drug fever

    Interactions: Concurrent administration of

    artemisinin compounds with terfenadine,

    astemizole, antiarrhythmics, TCA &

    phenothiazine may increase the risk of cardiac

    conduction defects

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