Anti-Mycobacterial Drugs Lecture Notes

Overview

• Focus on anti-mycobacterial drugs: their mechanisms, uses, and adverse effects.
• Importance of following along with additional resources linked in the description.

Mechanisms of Action

• Understanding the mechanism is crucial for exams.

1. Rifamycins

• Drugs: Rifampin, Rifabutin.
• Action: Inhibit RNA polymerase.
• Result: Decreased mRNA synthesis, leading to reduced protein synthesis, essential for bacterial survival.

2. Dapsone

• Action: Inhibits the conversion of para-aminobenzoic acid into dihydrofolate in nucleotide formation pathway.
• Result: Reduced nucleotide synthesis, essential for DNA and RNA replication.

3. Streptomycin

• Action: Inhibits the 30S ribosomal subunit.
• Result: Decreased protein synthesis.

4. Isoniazid

• Action: Activated by catalase-peroxidase, binds NAD; inhibits enol reductase.
• Result: Decreased synthesis of mycolic acid, essential for cell wall integrity.

5. Pyrazinamide

• Action: Inhibits fatty acid synthase involved in mycolic acid synthesis.
• Result: Reduced mycolic acid formation.

6. Ethambutol

• Action: Inhibits arabinosyl transferase.
• Result: Decreased synthesis of arabinogalactan, structural component of the cell wall.

Clinical Uses

Tuberculosis (TB)

• Latent TB Treatment:
  • Options: Isoniazid (6-9 months) or Rifampin (4 months).
• Active TB Treatment (RIPE regimen):
  • Rifampin, Isoniazid, Pyrazinamide, Ethambutol for 2 months.
  • Followed by Rifampin and Isoniazid for 4 months.
  • Important: Supplement with B6 to prevent neuropathy.

Leprosy

• Drugs: Dapsone, Rifampin (and sometimes Clofazimine).

Mycobacterium Avium Complex (MAC) Infections

• Treatment: Ethambutol, Rifampin, and a macrolide (Clarithromycin/Azithromycin).
  • In severe cases, consider adding aminoglycosides or fluoroquinolones.

Adverse Effects

Rifampin

• Red-orange urine (harmless), false positive urine opiate tests, CYP450 inducer.

Dapsone

• Methemoglobinemia, G6PD deficiency risk (acute hemolysis), potential for neutropenia.

Isoniazid

• Hepatotoxicity, potential for metabolic acidosis, drug-induced lupus, B6 deficiency leading to neuropathy or seizures.

Pyrazinamide

• Hepatotoxicity, hyperuricemia (watch in gout patients).

Ethambutol

• Optic neuritis (monitor vision).

Streptomycin

• Nephrotoxicity, ototoxicity, contraindicated in pregnancy and myasthenia gravis.

Key Points to Remember

• Always consider the specific mechanisms for each drug.
• Know the differences in treatment regimens based on the type of infection (latent vs. active TB).
• Be aware of the adverse effects and necessary monitoring for each drug.