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Questions and Answers
What is the mechanism of action of rifamycins?
Which drug is activated by catalase peroxidase within the mycobacterium?
What enzyme does dapsone inhibit in its mechanism of action?
What is a key component synthesized by enol reductase that is inhibited by the isoniazid-NAD complex?
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Which drug is typically included in the RIPE regimen for treating active tuberculosis?
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What is the purpose of B6 supplementation during isoniazid treatment?
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Which side effect is associated with Ethambutol?
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What does ethambutol inhibit in the synthesis of the mycobacterial cell wall?
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What effect does Rifampin have on urine color?
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Which drug combination is typically used to treat Mycobacterium Avium Intracellular Complex (MAC) infections?
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Which drug is often added for severe or disseminated cases of tuberculosis?
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What is a potential adverse effect of Isoniazid?
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Which drug should be monitored for nephrotoxicity?
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Which of the following drugs is primarily used for treating leprosy?
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Which regimen is recommended for treating latent TB?
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Which side effect might result from taking Pyrazinamide?
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What is a significant effect of Dapsone?
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What condition can result from Isoniazid use due to B6 deficiency?
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What is a major concern with the use of Streptomycin?
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Which treatment option is recommended for Mycobacterium avium complex?
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Study Notes
Anti-mycobacterial Drug Mechanisms of Action
- Rifamycins (Rifampin & Rifabutin) inhibit RNA polymerase, preventing the conversion of DNA to mRNA and ultimately protein synthesis, crucial for mycobacterium function.
- Dapsone inhibits the conversion of para-aminobenzoic acid (PABA) into dihydrofolate, a key step in the metabolic pathway for nucleotide synthesis, essential for DNA and RNA formation.
- Streptomycin binds to the 30S ribosomal subunit, preventing its interaction with mRNA, thereby inhibiting protein synthesis.
- Isoniazid is activated within the mycobacterium by catalase peroxidase (Cat G enzyme) to form an active metabolite that binds to NAD. This complex inhibits enol reductase, an enzyme responsible for mycolic acid synthesis, a component of the cell wall.
- Pyrazinamide inhibits fatty acid synthase, an enzyme involved in the synthesis of mycolic acid.
- Ethambutol inhibits arabinosyl transferase, an enzyme that converts arabinose and galactose into arabinogalactan, another crucial cell wall component.
Anti-Mycobacterial Drug Uses
-
Latent Tuberculosis (TB):
- Treated for 6-9 months with either isoniazid (INH) or rifampin (4 months).
-
Active Tuberculosis (TB):
- RIPE regimen for 2 months: rifampin, isoniazid, pyrazinamide, and ethambutol.
- After 2 months, continue with rifampin & isoniazid for 4 months.
- B6 supplementation is essential due to isoniazid's potential to cause B6 deficiency and neurotoxicity.
- Streptomycin may be added for severe or disseminated cases, primarily by infectious disease specialists.
-
Leprosy:
- Typically treated with dapsone and rifampin, sometimes with clofazimine for tuberculoid leprosy.
-
Mycobacterium Avium Intracellular Complex (MAC) Infections:
- Treated with ethambutol, rifampin, and a macrolide (clarithromycin or azithromycin).
- Aminoglycosides and fluoroquinolones may be added for severe or refractory cases.
Rifampin
- Causes red-orange urine: harmless but notable
- False positive urine opiate test: important to know for screening
- Cyp 450 inducer: can reduce efficacy of drugs like NNRTIs (HIV medication), switch to rifabutin for HIV+ patients
- May negatively interact with drugs metabolized by CYP450
Pyrazinamide
- Hepatotoxic: monitor liver function tests (LFTs)
- Hyperuricemia: increases uric acid in blood, potential for gout exacerbation
Ethambutol
- Optic neuritis: potential for visual disturbances, monitor and refer to ophthalmologist
Isoniazid
- Hepatotoxic: monitor liver function tests
- Anion gap metabolic acidosis: can cause both ketoacidosis and lactic acidosis
- Drug-induced lupus: remember the mnemonic SHIP (sulfa drugs, hydralazine, isoniazid, procainamide, phenytoin)
- B6 deficiency: can lead to neuropathy and anemia
- Seizures: may lower seizure threshold, can be refractory to benzodiazepines
Streptomycin
- Nephrotoxic: monitor renal function
- Ototoxic: can damage auditory and vestibular nerves, monitor hearing
- Teratogenic: avoid in pregnancy
- Contraindicated in Myasthenia Gravis: can worsen symptoms
Treatment Regimens
-
Latent TB:
- Isoniazid (INH) 6-9 months
- Rifampin (RIF) 4 months
-
Active TB:
- RIPE regimen (RIF, INH, Pyrazinamide, Ethambutol) for 2 months
- RH regimen (RIF, INH) for 4 months
- Add B6 (pyridoxine) to prevent INH-induced B6 deficiency
- Switch RIF to Rifabutin for HIV+ patients
- Miliary TB or TB meningitis: consider adding Streptomycin
MAC (Mycobacterium avium complex)
- Treatment: Rifampin/Rifabutin, Ethambutol, Macrolide (e.g., Azithromycin)
- Severe/Refractory Cases: add fluoroquinolones or aminoglycosides
Leprosy (Mycobacterium leprae)
-
Treatment:
- Dapsone and Rifampin
- Add Clofazimine for tuberculoid leprosy
Dapsone
- Methemoglobinemia: oxidizes hemoglobin, can cause hypoxia (lack of oxygen in tissues)
- G6PD deficiency: can cause acute hemolytic anemia
- Neutropenia: can suppress neutrophil production
Anti-mycobacterial Drug Mechanisms of Action
- Rifamycins (Rifampin & Rifabutin) block RNA polymerase, preventing protein synthesis, crucial for mycobacterium growth.
- Dapsone inhibits the formation of dihydrofolate, essential for DNA and RNA synthesis.
- Streptomycin binds to the 30S ribosomal subunit, preventing its interaction with mRNA and protein synthesis.
- Isoniazid is activated by catalase peroxidase (Cat G enzyme) to inhibit enol reductase, an enzyme responsible for mycolic acid synthesis, key for mycobacterium cell wall.
- Pyrazinamide inhibits fatty acid synthase, an enzyme for mycolic acid synthesis.
- Ethambutol inhibits arabinosyl transferase, preventing the production of arabinogalactan, crucial for cell wall integrity.
Anti-Mycobacterial Drug Uses
- Latent Tuberculosis (TB): Treated with isoniazid (INH) or rifampin for 6-9 months.
- Active Tuberculosis (TB): Treated with RIPE regimen (rifampin, isoniazid, pyrazinamide, and ethambutol) for 2 months followed by rifampin & isoniazid for 4 months.
- B6 supplementation is essential due to isoniazid's potential for B6 deficiency.
- Streptomycin may be added for severe or disseminated TB cases.
- Leprosy: Typically treated with dapsone and rifampin, sometimes including clofazimine for tuberculoid leprosy.
- Mycobacterium Avium Intracellular Complex (MAC) Infections: Treated with ethambutol, rifampin, and a macrolide (clarithromycin or azithromycin).
- Aminoglycosides and fluoroquinolones may be added for severe or refractory MAC infections.
Rifampin
- Causes red-orange urine: a harmless but notable side effect.
- Can cause false positive urine opiate tests: important for screening.
- Cyp 450 inducer: can reduce efficacy of drugs like NNRTIs (HIV medication).
- May interact with drugs metabolized by CYP450.
Pyrazinamide
- Hepatotoxic: monitor liver function tests (LFTs).
- Hyperuricemia: increases uric acid in blood, potential for gout exacerbation.
Ethambutol
- Optic neuritis: potential for visual disturbances, monitor and refer to ophthalmologist.
Isoniazid
- Hepatotoxic: monitor LFTs
- Anion gap metabolic acidosis: can cause both ketoacidosis and lactic acidosis
- Drug-induced lupus: remember the mnemonic SHIP
- B6 deficiency: can lead to neuropathy and anemia
- Seizures: may lower seizure threshold, can be refractory to benzodiazepines.
Streptomycin
- Nephrotoxic: monitor renal function.
- Ototoxic: can damage auditory and vestibular nerves, monitor hearing.
- Teratogenic: avoid in pregnancy.
- Contraindicated in Myasthenia Gravis: can worsen symptoms.
Treatment Regimens
-
Latent TB:
- Isoniazid (INH) 6-9 months
- Rifampin (RIF) 4 months
-
Active TB:
- RIPE regimen (RIF, INH, Pyrazinamide, Ethambutol) for 2 months
- RH regimen (RIF, INH) for 4 months
- Add B6 (pyridoxine) to prevent INH-induced B6 deficiency
- Switch RIF to Rifabutin for HIV+ patients
- Miliary TB or TB meningitis: consider adding Streptomycin
MAC (Mycobacterium avium complex)
- Treatment: Rifampin/Rifabutin, Ethambutol, Macrolide (e.g., Azithromycin)
- Severe/Refractory Cases: add fluoroquinolones or aminoglycosides
Leprosy (Mycobacterium leprae)
-
Treatment:
- Dapsone and Rifampin
- Add Clofazimine for tuberculoid leprosy
Dapsone
- Methemoglobinemia: oxidizes hemoglobin, can cause hypoxia (lack of oxygen in tissues).
- G6PD deficiency: can cause acute hemolytic anemia.
- Neutropenia: can suppress neutrophil production.
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Description
Explore the mechanisms of action of various anti-mycobacterial drugs including Rifamycins, Dapsone, Streptomycin, Isoniazid, Pyrazinamide, and Ethambutol. This quiz will test your understanding of how these drugs inhibit various processes critical for mycobacterial survival. Perfect for students of pharmacology and microbiology!
