Antimycobacterials Flashcards
Isoniazid
30-
Antimycobacterial - Tuberculosis
Tx: Actively growing TB (part of core therapy, given with another anti-TB), Latent TB (given alone)
Side Effects: Hepatotoxicity (highly correlated with increased age, adds to hepatotoxicity of other anti-TB, monitor hepatic function, acetylated by N-acetyltransferase-2 and metabolized into acetylhydrazine, which forms hepatotoxic intermediate), Neurotoxicity, esp. peripheral neuritis (increased risk in slow acetylators, improve with pyridoxine vitamin B6 admin since rx interferes with B6 function)
Mechanism: Inhibits synthesis of mycolic acid (outer membrane component) when activated by mycobacterial catalase-peroxidase (KatG), which inhibits enoyl-acyl protein carrier reductase (InhA)
Resistance: KatG mutation that does not activate rx, InhA mutation that does not bind to active rx, Increased resistance in larger cities with more international travel to TB-endemic areas
Pharmacology: Cidal for actively growing TB, both intra- and extracellular forms, N-acetylation under genetic control
Rifampin
30-01-16
Antimycobacterial - Tuberculosis
Tx: Disseminated TB (high lipophilicity, part of core therapy, given with other anti-TB)
Side Effects: Hepatotoxicity (more likely for long-term therapy to tx TB, not short term to tx conventional bacteria, adds to hepatotoxicity of isoniazid), Potent inducer of multiple CYPs (increased metabolism of 70% all rx), Orange-red color
Mechanism (same as conventional bacteria): Inhibits DNA-dependent RNA polymerase to suppress RNA synthesis
Pharmacology: Cidal for intra- and extracellular forms, NEVER used alone, Well-distributed (high lipophilicity), Metabolized in liver by deacetylation (CYP-mediated)
Antimycobacterial - Leprosy
Tx: Mycobacterium leprae (part of almost all anti-leprosy combos)
Tx regimens for leprosy
Tuberculoid disease = 1 yr, only 2 rx = dapsone + rifampin
Lepromatous disease = 2 yr, all 3 rx
Ethambutol
30-01-19
Antimycobacterial - Tuberculosis
Tx: TB (given with other anti-TB, NOT hepatotoxic)
Side Effects: Optic neuritis (reversible after rx stopped, decreased visual acuity, red-green blindness, low incidence of permanent blindness), Generally well-tolerated, NOT hepatotoxic (advantage when given in combo)
Mechanism: Prevents cell wall synthesis by inhibiting arabinosyl transferase, preventing arabinogalactin polymerizationResistance: Arabinosyl transferase mutation that does not bind rx
Pharmacology: Static if given alone, but does not interfere with other cidal rx, weakens outer membrane barrier to enhance rx entry, Affects both intra- and extracellular forms, Well absorbed and distributed (including CSF)
Pyrazinamide
30-01-21
Antimycobacterial - Tuberculosis
Tx: Disseminated TB into CNS, Short-term combo therapy for TB (part of core therapy)
Side Effects: Hepatic damage (adds to hepatotoxicity of other anti-TB, severe/fatal esp. when combined with rifampin = PZA withdrawn after 2 mo to minimize hepatic damage)
Mechanism: Blocks mycolic acid synthesis by inhibiting fatty acid synthase I
Pharmacology: Cidal for intra- and extracellular forms, Well-absorbed, Widely distributed, including CNS
Streptomycin
30-01-23
Antimycobacterial - Aminoglycoside (Tuberculosis)
Tx: Reserved for most serious TB forms, e.g. disseminated, advanced (least used 1st line agent due to high toxicitiy, only initial therapy before withdrawn after two weeks as bacterial number reduced)
Side Effects (all aminoglycosides): Ototoxicity (hearing and balance), Nephrotoxicity
Mechanism: Binds to several ribosomal sites at 30S/50S interface, stopping initiation and inducing mRNA misreading
Pharmacology: Cidal for extracellular forms ONLY
Rifabutin
30-01-30
Antimycobacterial - Atypical Mycobacteria (MOTT)
Tx: Single-agent prophylaxis of M. avium intracellulare (MAC) in AIDS pts, Alternate to rifampin for mult-rx tx MAC or rifampin-resistant TB
Side Effects: Similar to rifampin but less frequent, Less potent CYP inducer = rx intxn lesser extent
Mechanism:
Pharmacology: Lipophilic rifampin analog, MAC less fatal than TB, so AFB but no ID yet = assume TB and institute anti-TB regimen until ID, then can switch if MAC ID
Antimycobacterial - Leprosy
Clarithromycin
30-01-32
Antimycobacterial - Atypical Mycobacteria (MOTT)
Tx: MAC in AIDS pt (multi-rx regimen, both prophylaxis and tx)
Side Effects: Inhibits CYP3A4, but NO CYP induction (potential advantage over rifabutin, does NOT intxt with anti-HIV)
Pharmacology: Cidal for MAC, even for intracellular forms (static for conventional bacteria)
Dapsone
30-01-37
Antimycobacterial - Leprosy
Tx: Mycobacterium leprae (combo w/other rx), Alternative to TMP/SMX (first line) for prophylaxis and tx Pneumocystis jiroveci (carinii) in AIDS pts
Side Effects: Both dose dependent (more common at higher doses), Hemolytic anemia, Methomoglobinemia (iron and Hb converted to Fe3+ = does NOT transport O2)Mechanism: Structural analog of p-aminobenzoic acid (PABA) that blocks dihydropteroate synthase and inhibits folic acid synthesis (similar to isoniazid)
Pharmacology: Static, Metabolized by NAT-2, Slow and fast acetylators
Clofazimine
30-01-39
Antimycobacterial - Leprosy
Tx: Mycobacterium leprae (incl. dapsone-resistant leprosy, combo therapy only), MAC in AIDS pts (combo therapy)
Side Effects: Red-brown pigmentation of skin, Generally well-tolerated
Mechanism: Binds to DNA, interfering with reproduction and growth (not well understood)
Pharmacology: Highly lipophilic, Longest half-life (2 mo)
Ciclopirox
31
Antifungal
Tx: Mild to moderate fungal nail infxn (ONLY FDA approved topical rx, often toenail infxn since feet in shoes = warm and moist envt)
Side Effects: N/A
Mechanism: Possibly inhibits metal-dependent fungal enz by metal chelation to prevent infxn of new tissue as new nail grows out (one year), NO eradication
Pharmacology: Static, Forms = topical
Griseofulvin
31-02-22
Tx: Recalcitrant dermatophytic infxn of skin, hair, nails, Therapy for children (esp. for tinea capitis)
Side Effects: Well-tolerated, Increased metabolism of several rx (CYP inducer), Contraindicated in pts with porphyria and advanced liver disease, Use with caution in pts with penicillin allergies (produced in Penicillium)
Mechanism: Interferes with microtubule function/mitotic spindle/mitosis, stopping growth and preventing infxn of new tissue (NO eradication)
Pharmacology: Form = oral
