TB Drugs Flashcards
Isoniazid Importance Use Type of AB Mechanism Resistance Duration Metabolism Adverse rxns Precautions
Most important TB drug
Used for active and latent infections
Bactericidal
•Mechanism – Prodrug. Activated by KatG to isonicotinoyl radical, which reacts w/ NAD and NADP, decreasing synthesis of mycolic acid (cell wall) and dihydrofolate reductase (DHFR, nucleic acid synthesis)
•Resistance - mutations in NADH-dependent acyl carrier or katG.
•Given for 6-12 months. 9 months for latent infection.
•Metabolism – slow vs fast acetylators. N-acetyl transferase.
•Adverse rxns – elevated LFTs (stop above 3x), hepatitis, peripheral neuropathy due to pyridoxine (Vit B6) depletion. More likely in slow acetylators.
•Precautions – hepatitis, monitor LFTs, supplement w/ Vit B6
Rifampin Use Type of AB Mechanism Resistance Duration Adverse rxns Precautions
TB. DOC for leprosy, prophylaxis of H flu meningitis, and meningococcus.
Broad spectrum, bactericidal.
•Mechanism – binds RNA polymerase, inhibiting RNA synthesis.
•Resistance – mutations → reduced binding to RNA polymerase
•Given for 6-9 months for TB.
•Adverse rxns – flu-like sxs, strong inducer of CYP enzymes (reduces action of other drugs), orange discoloration of sweat / tears.
•Precautions – hepatic disease, don’t use w/ HIV pxs on protease inhibitors.
Ethambutol Type of AB Mechanism (3 things) Duration Adverse rxns Precautions
Bacteriostatic - only works against actively dividing cells.
•Mechanism – blocks arabinosyl transferase to block cell wall synthesis, inhibits RNA synthesis, and interferes w/ mycolic acid synthesis
•Given for 6-9 months. Does not reduce length of tx, but covers different resistances.
•Adverse rxn – Optic neuritis (causing decreased visual acuity and red/green color blindness, usually reversible). Don’t use in kids b/c it is difficult to assess acuity.
•Precautions – optic neuritis (mainly), gout (interferes w/ uric acid excretion)
Pyrazinamide Type of AB Mechanism ( 3 things) Duration Adverse rxns Precautions
Bacteriostatic at low conc. Bactericidal at high conc.
•Mechanism – Prodrug activated to pyrazinoic acid. Active against mycobacteria living in lysosomes. 3 proposed mechanisms. 1) inhibits FA synthetase, 2) reduces intracellular pH, 3) disrupts membrane transport
•Given for first 2 months in combination w/ isoniazid and rifampin to reduce total therapy time to 6 months.
•Adverse rxns – hepatotoxicity (most serious), hyperuricemia (interferes w/ uric acid excretion)
•Precautions – hepatic disease (mainly), gout
2nd line drugs
Aminoglycosides, moxifloxacin, and bedaquiline
Aminoglycoside AB's Examples Use Mechanism Resistance Toxicity
- Ex: gentamicin, neomycin, streptomycin. All are amino sugars.
- Mainly act against aerobic GNR’s (E coli, Klebsiella, Pseudomonas)
- Mechanism – binds 30S ribosome subunit to block protein synthesis
- Resistance - inactivating enzymes, mutations to ribosome subunits, and efflux pumps
- Toxicity – ototoxicity (CN VIII damage → hearing and balance problems), nephrotoxicity, NMJ blockade, skin rxns / contact dermatitis, Pregnancy D
General mechanism of FQ’s
Inhibit topoisomerase
Moxifloxacin Type of AB Use Mechanism Resistance Adverse rxns Precautions
Broad-spectrum FQ.
Used for allergy / resistance to 1st line drugs. Decreases tx time when added to 4-drug regimen.
•Mechanism – Inhibits DNA duplication / transcription / repair by stabilizing topoisomerase
•Resistance occurs via mutations in topoisomerase and efflux pumps
•Adverse rxns – well tolerated. Some QT lengthening and myasthenia gravis worsening due to NMJ blockade.
•Precautions – prolonged QT and myasthenia gravis
Bedaquiline Use Mechanism Adverse rxns Precautions
Used in adults w/ MDR-TB. Combined w/ at least 3 other drugs.
•Mechanism – binds mycobacterial ATP synthase subunit C, which prevents rotation, and thus ATP synthesis.
•Adverse rxns – QT prolongation
•Precautions – do ECG at baseline and every couple weeks to detect long QT
Dapsone
Use
Mechansim
Tx leprosy
Inhibits folate synthesis
2 phases of TB tx
How long does each last?
When is px changed from one to next?
- Initial (active) phase reduces mycobacterial mass. Usually 2 months.
- Continuation (suppressive) phase prevents relapse. Usually 4 months.
- Disappearance of bacilli from sputum (culture conversion) triggers switch in regimens.
