Antimycobacterial Antibiotics Flashcards
Rifamycins
Rufamycins:
Drugs:
- Oral or IV rifampin (rifampicin)
- Oral rifabutin
Mechanism of action:
- Obstruct bacterial protein synthesis by inhibiting bacterial DNA-dependent RNA-polymerase, thus preventing transcription
- Bactericidal
CNS penetration:
- Only when meninges are inflamed
Route of elimination:
- Biliary
Clinical use:
- Mycobacteria
- Tuberculosis
- In combination with dapsone and clofazimine: leprosy
- Haemophilus influenzae type b prophylaxis
- Gram-negative coccobacillus that can cause life-threatening acute epiglottitis in children
- Meningococcal prophylaxis
Adverse effects:
- Harmless orange discolouration of body fluids (e.g., urine, tears)
- Flulike symptoms (fever, arthralgia and in severe cases hemolytic anemia, thrombocytopenia, renal failure)
- Hepatotoxicity
- Resistance develops rapidly if used as monotherapy.
- CYP induction (CYP3A4, CYP2C9)
Contraindications:
- Hepatic failure (relative contraindication)
- Pregnancy (relative contraindication)
The 4Rs’ of rifampin: RNA polymerase inhibition, Ramping up of cytochrome P450 activity, Red or orange coloured urine, and Rapid development of resistance if used alone
Isoniazid
Mechanism of action:
- Prevents cell wall synthesis by inhibiting the synthesis of mycolic acid
- Bactericidal
CNS penetration:
-Variable (20–100% of serum concentration)
Route of elimination:
- Renal
Clinical use:
- Treatment and prophylaxis of M. tuberculosis; first-line for monotherapy of latent TB
Adverse effects:
- Hepatotoxicity
- Drug-induced lupus erythematosus
- Vitamin B6 deficiency (should be combined with pyridoxine to avoid these adverse effects) (Causes peripheral neuropathy, sideroblastic anemia, aplastic anemia, thrombocytopenia and optic neuropathy)
Contraindications:
- Hepatic failure (relative contraindication)
- Pregnancy (relative contraindication)
**INH Injures Neurons and Hepatocytes!
**Neurotoxicity and lupus may be prevented by supplementing with pyridoxine (vitamin B6)!
Pyrazinamide
Mechanism of action:
- Not completely understood.
- Bactericidal
CNS penetration:
- Only when meninges are inflamed
Route of elimination:
- Renal
Clinical use:
- M. tuberculosis
Adverse effects:
- Hyperuricemia → gout
- Hepatotoxicity
Contraindications:
- Hepatic failure (relative contraindication)
- Pregnancy (relative contraindication)
Ethambutol
Mechanism of action:
- Prevents cell wall synthesis by inhibiting arabinosyltransferase
- Bacteriostatic
CNS penetration:
- Only when meninges are inflamed
Route of elimination:
- Primarily renal
Clinical use:
- M. tuberculosis
- M. avium-intracellulare
Adverse effects:
- Optic neuritis, retrobulbar neuritis → ↓ visual acuity and red-green color-blindness→ can result in irreversible blindness
- Resistance develops rapidly if used as a monotherapy.
Contraindications:
- Children (relative contraindication)
**EYEthambutol causes optic neuropathy!
Dapsone
Mechanism of action:
- Prevents synthesis of folic acid by acting as a competitive antagonist of para-aminobenzoic acid (PABA)
- Bactericidal or bacteriostatic
Route of elimination:
- Mostly renal
Clinical use:
- M. leprae
- Alternative to TMP/SMX for the prophylaxis of P. jiroveci pneumonia
- Alternative to sulfadiazine + pyrimethamine for toxoplasmosis
- In combination with pyrimethamine as an alternative to standard therapy for chloroquine-resistant malaria
Adverse effects:
- Methemoglobinemia
- Triggers haemolytic anemia in G6PD-deficient patients
- Gastrointestinal side effects
- Peripheral neuropathies
Contraindications:
- Patients with G6PD deficiency
