Antimycobacterial agents Flashcards
Impact of mycobacterial growth and physiology on effective tx of mycobacterial infections
acid fast stain, rod shaped
grow intracellularly so need drugs to go into cell
Slow growing - dormancy within granulomas, replicate in macrophages - efffects how quickly drugs work
Emergence of multidrug resistant TB and its implications for the tx of infection
things havent improved in last 20 years
about 10% resistant to isoniazid
and 1-3% multi drug resistant
First line anti TB drugs and explain their MOA
- Rifampin - member of rifamycin family, inhib RNA synthesis of bacteria, into tissue well, for active TB also alternative for latent TB, resistant is 1 in a million, well absorbed, quick peak, widely distributed,
- Isoniazid - inhib things that produce mycolic acid, bacteriocydal, penetrates macrophage (active against both extra/intracellular organisms), less effective against atypical m. avium, looks like pyridoxine (B6). Is a prodrug, safest/most effective
Resistance is usually mut in Kat G - no activation of prodrug, overexpress of Inh A protein, always use 2 drugs when tx active TB, good absorption, peaks quick, It is acetylated in liver - doesnt effect its effectiveness, however slow acetylators are more likely to develop toxicity - Ethambutol - inhib mycolic acid by inhib arabinosyl transferase, rarely on its own, multidrug tx, M. Avium tx, Pt mutations in genes for arabinosyl transferase infers resistance, well absorbed/dist
- Pyranzinamide - inhiib mycolic acid maybe, exculsively in multidrug tx, prodrug conv by pyrazinomydase, when TB is in macrophages it is acidic - this attacks well, for ACTIVE TB, resistance sometimes from mut in pyrazinomidase enzyme, well absorbed/distributed, gets into the macrophages
If multidrug resistance
Streptomyciin: Interferes iwth protein synthesis, doesnt’ get into the macrophage very well, use is act of desperation, Injectable, poor tissue penetration
List drugs used in treating leprosy and their MOA
Multidrug - multi years - 5
- Dapsone - inhib folic acid synth, concentrates in skin
- Clofazimine - dye, intercalates into bacterial DNA, buildup in fat, reddish brown skin
- Rifampin
Describe the adverse effects of first line antiTB drugs
- Isoniazid: Hepatitis from inc in liver enzymes, risk increases in older indiv/alcoholics, Peripheral Neuropathy - seen more in slow metabolizers and malnourished/alcoholic/diabetic/aids, supplement with B6
- Rifampin: GI disturbance, Nervous symptoms, Hepatitis, Red/Orange color in urine/feces/sweat/tears/saliva, strong inducer of CYP450s, increases metabolism of other drugs, especially antiretrovirals, use Rifabutin in HIV patients, same family but less rxn with CYP450s,
Describe recommended tx of infections caused by M. Avium complex
Combination tx
- Rifampin (or rifabutin for HIV)
- Macrolide abx
- Ethambutol
Explain the considerations necessary when tx patients on antiretroviral therapy
Rifampin induces the CYP450 system which increases the metabolism of other drugs including antiiretroviral drugs. so in pnts with HIV, substitute with Rifabutin - which is a less potent inducer of CYP450
Describe the adverse effects of first line antiTB drugs
- Isoniazid: Hepatitis from inc in liver enzymes, risk increases in older indiv/ALCOHOLICS, Peripheral Neuropathy - seen more in slow metabolizers and malnourished/alcoholic/diabetic/aids, supplement with B6
- Rifampin: GI disturbance, Nervous symptoms, Hepatitis, Red/Orange color in urine/feces/sweat/tears/saliva, strong inducer of CYP450s, increases metabolism of other drugs, especially antiretrovirals, use Rifabutin in HIV patients, same family but less rxn with CYP450s,
- Pyrazinamide - Hepatotoxicity (ALCOHOLICS), Hyperuricemia - small percentage develop gout
- Ethambutol - Retrobulbar Neuritis (rare in kids mostly, impaired vision, red green color blind), Hyperuricemia (small % get gout)
Streptomycin: Ototoxicity and Neurotic
