Antimycobacterials

Question 1

Treatment of TB First-Line Drugs

Answer 1

Isoniazid
Rifampin
Ethambutol
Pyrazinamide
Streptomycin

Question 2

Isoniazid

Answer 2

Adverse side effects: Neurotoxicity (esp. peripheral neurtitis) with slow acetylators but if given with pyridoxine (B6) then improved
Hepatotoxicity (10-20%)

Question 3

Isoniazid Mechanism of Action

Answer 3

cidal for actively growing bacilli and inhibits mycolic acid
drug is activated by catalase peroxidase (KatG protein) and targets the enoyl-acyl carrier protein reductase (InhA protein)

Question 4

Rifampin

Answer 4

MoA: inhibits DNA-dependent RNA polymerase thereby suppressing RNA synthesis
Cidal for intra and extraceullar forms
Use in combination
Adverse effects: hepatotoxicity, potent inducer of multiple CYPs caused increased metabolism of other drugs (3A4, 2C9, 2C19, 1A2), orange-red color

Question 5

Ethambutol

Answer 5

MOA: interferes with arabinosyl transferase, blocking cell wall synthesis
Tuberculostatic
Spont. resistance so use in combination
Distribute to CSF
Side effects: optic neuritis (5-15%), no hepatotoxic

Question 6

Pyrazinamide (PZA)

Answer 6

MOA: blocks mycolic acid synthesis by inhibiting fatty acid synthase 1
Cidal
Use in combination (important component for short-term therapy)
Well distributed in CNS (useful drug for central CNS involvement)
Adverse effects: Hepatic damage (and fatal potentially when used with rifampin)
Rifampin+pyrazinamide are effective combination

Question 7

Streptomycin

Answer 7

Aminglycoside
MoA: bind to several ribosomal sites (30S/50S) and stops initiation and causes mRNA misreading
Cidal
Usually reserved for most serious forms of TB
Adverse effects: Ototoxicity, Nephrotoxicity

Question 8

Multi-Drug Regimens for Treating TB

Answer 8

Short-course: uncomplicated pulmonary TB–> isoniazid plus rifampin plus pyrazinamide
Disseminated TB or potential drug -resistant strain–> rifampin plus isoniazide plus pyrazinamide and ethambutol
Toxic drugs used initially for short periods of time

Question 9

Eradication vs. Stasis of TB infections

Answer 9

Intracellular and extracellular and Bactericidal :
Isoniazid
Rifampin
Pyrazinamide

Question 10

M. Avium intracellulare complex (MAC)

Answer 10

opportunistic infections in AIDS

MAC less fatal than TB so if find ADP then institute anti-TB regimen until agent is identified

Question 11

Rifabutin

Answer 11

Treat MAC
Single agent prophylaxis of MAC in AiDS patients
Also alternate to rifampin for multi-drug treatment of MAC
Side effects: similar to rifampin but less frequent and drug interactions similar to rifampin but to al esser extent (less potent CYP inducer)

Question 12

Clarithromycin

Answer 12

Treat MAC
Part of multi-drug regiment for treatment of MAC in AIDS patients
Also for MAC prophylaxis
Cidal even in intracellular forms for MAC

Question 13

Leprosy (Hansen’s Disease)

Answer 13

Causative agent: mycobacterium leprae
2 major types: lepromatous and tuberculoid
Only specialists should treat leprosy; National Hansen’s Disease Program in Baton Rouge, Louisiana

Question 14

Dapsone

Answer 14

Treat Leprosy
MOA: Structural analog of para-ambobenzoic acid (PABA); inhibits downstream synthesis of folic acid
Bacteriostatic
Use in combination with other drugs
Alternative for prophylaxis of Pneumocystis jivoreci in AIDS patients
Metabolism- slow and fast acetylators
Adverse effects: hemolytic anemia, methemglobinemia

Question 15

Treatment for Leprosy

Answer 15

Dapsone
Clofazimine
Rifampin

Question 16

Clofazimine

Answer 16

MoA: binds to DNA, interferes with reproduction and growth
Combination therapy
Side effects: red-brown pigmentation of the skin