Podcast
Questions and Answers
What is one of the primary mechanisms of resistance to Isoniazid?
What is one of the primary mechanisms of resistance to Isoniazid?
Which drug interaction is associated with Isoniazid?
Which drug interaction is associated with Isoniazid?
Which of the following is a notable adverse effect of Rifampicin?
Which of the following is a notable adverse effect of Rifampicin?
Which of the following drugs is considered a first-line drug for the treatment of tuberculosis?
Which of the following drugs is considered a first-line drug for the treatment of tuberculosis?
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What occurs if Rifampicin is used alone in treatment?
What occurs if Rifampicin is used alone in treatment?
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What can high doses of Isoniazid potentially lead to?
What can high doses of Isoniazid potentially lead to?
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Rifampicin primarily inhibits which enzyme in bacteria?
Rifampicin primarily inhibits which enzyme in bacteria?
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How does Isoniazid interact with pyridoxine?
How does Isoniazid interact with pyridoxine?
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Which mechanism of resistance is associated with mutations in the katG gene?
Which mechanism of resistance is associated with mutations in the katG gene?
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Which adverse effect is most commonly associated with Pyrazinamide?
Which adverse effect is most commonly associated with Pyrazinamide?
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Which drug class does Levofloxacin belong to as a second line treatment for tuberculosis?
Which drug class does Levofloxacin belong to as a second line treatment for tuberculosis?
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What is the role of the embCAB gene in tuberculosis resistance?
What is the role of the embCAB gene in tuberculosis resistance?
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Which of the following drugs is not recommended for use during pregnancy?
Which of the following drugs is not recommended for use during pregnancy?
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Which adverse effect can be precipitated by Ethambutol?
Which adverse effect can be precipitated by Ethambutol?
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Which mechanism is involved in the resistance against the drug that inhibits DNA synthesis in tuberculosis?
Which mechanism is involved in the resistance against the drug that inhibits DNA synthesis in tuberculosis?
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Which second-line drug is known to inhibit the folate pathway?
Which second-line drug is known to inhibit the folate pathway?
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Study Notes
Tuberculosis Treatment
-
First Line Drugs (FLDs): Oral drugs used for initial treatment
- Isoniazid (INH/H)
- Rifampicin (R)
- Pyrazinamide (Z)
- Ethambutol (E)
Isoniazid (INH)
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Mechanism of Action: Inhibits cell wall synthesis by interfering with mycolic acid synthesis
- Structurally related to vitamin B6
- Activated by KatG in M. Tuberculosis
- Effective on both intracellular and extracellular bacilli
- Resistance Mechanism: Mutations in catalase peroxidase and the promoter gene inhA
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Pharmacokinetics: Penetrates body fluids, accumulates in caseated lesions
- Acetylated in the liver, resulting in faster elimination of the acetyl form
- Uses: Combined with other drugs for treatment; used alone for prophylaxis
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Adverse Effects:
- Allergic reactions
- Hepatotoxicity (increased risk with age, alcohol, drug use)
- Peripheral neuropathy (with high doses), minimized with pyridoxine
- Inhibits metabolism of other drugs (e.g., diphenylhydantoin)
- Drug Interactions: Alcohol and certain medications (e.g., phenytoin, carbamazepine) can affect INH absorption and metabolism
Rifampicin, Rifapentine, Rifabutin
- Mechanism of Action: Inhibits DNA-dependent RNA polymerase
- Bactericidal: Effective against various bacteria (including M. tuberculosis, M. leprae, and others)
- Resistance: Can develop quickly with monotherapy due to mutations in the rpoB gene
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Pharmacokinetics: Well absorbed orally; highly protein-bound; excreted primarily via liver and bile
- Induces hepatic microsomes and therefore affects the metabolism of other drugs
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Adverse effects: Hepatitis (dose-dependent and reversible)
- Nausea, vomiting, dizziness, fatigue, fever, jaundice
- Urine discoloration
- Drug Interactions: Induces metabolism of other drugs like oral contraceptives, anticoagulants, protease inhibitors
Ethambutol (Myambutol)
- Mechanism of Action: Inhibits arabinosyl transferases involved in cell wall biosynthesis
- Mechanism of Resistance: Mutations in embB gene
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Adverse Effects:
- Reversible retrobulbar neuritis (visual impairment)
- Red-green colour vision loss
- Mild gastrointestinal (GI) disturbances
- Potential for gout precipitation (due to decreased urate secretion)
Pyrazinamide
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Mechanism of Action:
- Derivative of nicotinamide
- Converted to pyrazinoic acid by bacterial pyrazinamidase
- Bactericidal, active in acidic environments of macrophage phagosomes (pH 5)
- Resistance Mechanism: Mutations in the pcnA gene (which encodes pyrazinamidase)
- Adverse Effects: Hepatotoxicity, vomiting, anorexia
- Special Considerations: Not recommended for use during pregnancy
- Action on TB: Acts on extracellular tubercle bacilli
- Other Considerations: Hepatotoxicity is a major concern; inhibits urate excretion and can precipitate gout attacks
Second-Line Drugs (SLDs)
- Fluoroquinolones: Levofloxacin, Moxifloxacin, Gatifloxacin
- Other SLDs: Ethionamide, Prothionamide, Cycloserine, Terizidone, Para-aminosalicylic Acid (PAS), Thiacetazone
MIC and Mechanism of Action Table
- Data on Minimum Inhibitory Concentration (MIC), genes involved in resistance, roles in resistance, and mechanism of action for various antituberculosis drugs.
Tuberculosis Treatment Categories
- Detailed descriptions of different treatment categories for latent and active tuberculosis infections, including specific drug combinations and durations.
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Description
This quiz covers key aspects of Isoniazid, a first-line drug used in tuberculosis treatment. Topics include its mechanism of action, resistance mechanisms, pharmacokinetics, uses, and potential adverse effects. Test your knowledge on how this vital medication contributes to effective TB therapy.
