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Flashcards in TB Drugs Deck (11):
1

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

2

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.

3

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)

4

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

5

2nd line drugs

Aminoglycosides, moxifloxacin, and bedaquiline

6

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

7

General mechanism of FQ's

Inhibit topoisomerase

8

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

9

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

10

Dapsone
Use
Mechansim

Tx leprosy
Inhibits folate synthesis

11

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.