Aaaa Tb Drugs

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first line agents for TB

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isoniazid, rifampin, pyrazinamide, ethambutol, streptomycin

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2nd line agents for TB

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amikacin, cipro, levofloxacin, rifabutin, rifapentine, ethionamide, cycloserine, capreomycin, P-aminosalicylic acid

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MDR TB

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strains resistant to at least the two main first line TB drugs- isoniazid and rifampicin

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XDR TB

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also resistant to the best second line drugs, fluroroquinolones and at least one of three injectible drugs such as amikacin, kanamycin or capreomycin

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isoniazid

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most active drug and good penetration of macrophages

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MOA and MOR of isoniazid

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inhibits synthesis of mycolic acids by targeting inhA,,,,, mutation of inhA gene, mutation of katG gent

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pharmokinetic prop of isoniazid

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liver metabolism, inhibits p450

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adverse reactions of isoniazid

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increased serum aminotransferase, hepatotox, peripheral neuropathy, seizure by decreasing GABA

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contraindications of isoniazid

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allergy, previous isoniazid induced hepatotox, acute liver disease

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MOA rifampin

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inhibits RNA synthesis by binding to the b subunit of bacterial RNA polymerase

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MOR rifampin

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point mutations of rpoB gener

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clinical usesof rifampin

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active tb, alternative to isoniazid prophylaxis, leprosy

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adverse reactions of rifampin

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reddish color in urine sweat tears, rashes, renal failure, hepatitis, thrombocytopenia

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drug interactions

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inducer of most p450 enzymes

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moa ethambutol

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inhibits mycobacterial arabinosyl transferase, interferes with the polymerization of arabinoglycan

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pharmacokinetics

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accumulate in renal failure

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adverse reactions of ethambutol

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dose related retrobulbar neuritis

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pyrazinamide

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prodrug, active against mycobacteria in the acidic lysosomes

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mor pyrazinamide

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mutations in the pncA gene

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adverse reactions of pyrazinamide

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hepatotox, hyperuricemia, polyarthralgia

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whats in rifater

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isoniazid, rifampin, pyrazinmide

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whats in 4-FDC

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isoniazid, rifampin, pyrazinamide, ethambutol

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MOA and clinical use of streptomycin

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aminoglycoside, irreversible inhibition of 30s ribosome, used as an injectable drug

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adverse rxn of streptomycin

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ototox and nephrotox

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amikacin

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aminoglycoside, used for streptomycin resistant TB

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ciprofloxacin and levoflox

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fluoroquinolones, active against m tuburculosis and atypical mycobacteria

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Fifabutin

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inhibit bacterial RNA polymerase, less potent inducer of p450 enzymes, good for hiv infected patients

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rifapentine

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potent inducer of p450 enzymes, avoided in hiv pts, inhibits bacterial RNA polymerase

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ethionamide

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blocks the synthesis of mycolic acid

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aminosalicylic acid

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folate synthesis antagonist

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capreomycin

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protein synthesis inhibitor, injectible for drug resistant TB, adverse rxn are nephrotox and ototox

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cycloserine

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inhibits cell wall synthesis, peripheral neuropathy, cns dysfunction… taken with pyridoxine and serum concentration should be monitored

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treatment for m avium complex (MAC)

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clarithro or azithro+ethambutol with or without rifabutin

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two forms of leprosy

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tuburculoid- PB milder… lepromatous- MB severe

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pb leprosy drugs

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rifampin, dapsone

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mb leprosy drugs

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rifampin, dapsone, clofazimine

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dapsone

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inhibit folate synthesis and dihydropteroate syntheatase, adverse rxn, hemolysis, g6pd, erythema nodosum leprosum

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rifampin

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inhibits rna polymerase, induces p450 enzymes

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clofazimine

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used for sulfone resistant leprosy, adverse rsn, gi intolerance dry skin and discoloration

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m leprae drugs

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dapsone plus rifampin plus clofazimine

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alternative second line drugs for TB

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amikacin, rifabutin rifapentine, cipro, levo, ethionamide, p aminosalacylic acid, capreomycin, cycloserine