Exam One Antimycobacterial MOA, AE, USE

Question 1

• Therapeutic Use: Most active TB drug in 4 drug combo.
• MOA: oral Prodrug (acetylated by liver), blocks mycolic acid synthesis killing the cell.
• AE Toxicity: hepatitis and necrosis and hepatocellular damage.
• Resistance: Over-expression of InhA gene, mutation (katG, ahpC, kasA).
• Notes: Well distributed and crosses BBB. Don’t give if pregnant. Peripheral neuropathy, CNS effects.

Answer 1

Isoniazid (INH)

Question 2

• Therapeutic Use: Bacteriostatic in 4 drug combo against TB.
• MOA: inhibits arabinosyl transferase enzymes preventing cell wall synthesis.
• AE Toxicity: Can cause red-green color blindness, retrobulbar neuritis is most serious SE.
• Resistance:
• Notes: Reaches CSF in meningeal inflammation

Answer 2

Ethambutol

Question 3

• Therapeutic Use: used in 4-drug combo against TB.
• MOA: unknown, sterilizing agent to prevent relapse.
• AE Toxicity: Hepatotoxicity, GI problems, hyperuricemia
• Resistance: pncA mutations blocking drug activation
• Notes: synthetic of nicotanimide

Answer 3

Pyrazinamide

Question 4

• Therapeutic Use: Used in 4 drug combo against TB
• MOA: Oral, Inhibits RNA synthesis (bactericidal)
• AE Toxicity: proteinuria, rash, nephritis, flu-like symptoms
• Resistance: rpoB mutation causing inability to bind RNA pol. Some resistance in ALL populations.
• Notes: analog of rifamycin. Take on empty stomach. Crosses BBB
• Makes urine, feces, saliva, sweat, and tears a red orange color!

Answer 4

Rifampin

Question 5

• Therapeutic Use: TB meningitis, MAC, M. kansaii and other mycobacteria.
• MOA: Unknown, effective against extracellular bacilli, used when injectable therapy required, crosses BBB
• AE Toxicity: oto-, nephrotoxicity, impaired renal function.
• Resistance: mutation in rpsL, rrs altering rRNA binding site.
• Notes: use when TB is resistant to other drugs.
Always give in multidrug therapy

Answer 5

Streptomycin

Question 6

• Therapeutic Use: TB
• MOA: Folate synthesis antagonist
• AE Toxicity: GI irritation and hypersensitivity reactions
• Resistance:
• Notes:

Answer 6

p-Aminosalicylic acid

Question 7

• Therapeutic Use: M. leprae (leprosy)
• MOA: inhibit folate synthesis
• AE Toxicity: hemolysis
• Resistance:
• Notes: Use clofazimime in dapsone resistant or allergic pt. Dapsone is sulfone-like. Armadillos!

Answer 7

Clofazimine