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General Information:
Pyrazinamide is an essential first-line anti-tuberculosis (TB) medication used in combination with other drugs for the treatment of Mycobacterium tuberculosis infections. It is a prodrug that is converted into its active form, pyrazinoic acid, within the bacterial cell, disrupting bacterial growth.
Chemical Properties:
Chemical Name: Pyrazine-2-carboxamide
Molecular Formula: CHNO
Molecular Weight: 123.11 g/mol
CAS Number: 98-96-4
Appearance: White to pale yellow crystalline powder
Solubility: Soluble in water and ethanol, slightly soluble in ether
Melting Point: 189192C
Mechanism of Action:
Pyrazinamide is a prodrug that is activated by bacterial pyrazinamidase (PncA) to pyrazinoic acid (POA), which disrupts membrane potential and intracellular pH homeostasis in Mycobacterium tuberculosis, leading to bacterial cell death. It is most effective in acidic environments, making it especially useful against TB bacteria in macrophages and necrotic lung lesions.
Pharmacokinetics:
Absorption: Well absorbed orally
Metabolism: Primarily metabolized in the liver to pyrazinoic acid
Excretion: Eliminated through urine (mainly as metabolites)
Half-life: 910 hours (may be prolonged in renal impairment)
Therapeutic Uses & Indications:
Treatment of active tuberculosis (TB)
Always used in combination with other TB drugs (e.g., rifampicin, isoniazid, ethambutol) to prevent drug resistance
Works effectively against dormant TB bacteria within acidic lesions
Dosage & Administration:
Adults:
Standard dose: 1530 mg/kg per day (maximum 2 g/day)
Intermittent therapy (twice weekly): 5070 mg/kg
Pediatric dosage: 1530 mg/kg per day
Administration: Taken orally, usually once daily with food to reduce gastrointestinal side effects
Side Effects:
Hepatotoxicity (most serious risk) liver enzyme elevation, jaundice, hepatitis
Hyperuricemia (may cause gout attacks)
Gastrointestinal disturbances nausea, vomiting, loss of appetite
Arthralgia (joint pain)
Skin rash, photosensitivity
Precautions & Contraindications:
Contraindicated in:
Severe liver disease
Acute gout
Use with caution in:
Patients with kidney impairment
Pregnant or breastfeeding women (only if benefits outweigh risks)
Drug Interactions:
Rifampicin & Isoniazid: Increased risk of liver toxicity
Allopurinol & Probenecid: May affect uric acid levels
Alcohol: Increases liver toxicity risk
Storage & Stability:
Store at room temperature (1530C)
Keep in a tightly closed container, away from light and moisture
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