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PYRAZINAMIDE - Mechanism, Resistance, Pharmacokinetics, Clinical Uses, Adverse Effects. (Urdu/Hindi)

Pyrazinamide is a synthetic pyrazine analog of nicotinamide. It is also called as pyrazinoic acid amide, pyrazine carboxylamine, pyrazinecarboxyamide. It is a prodrug that is activated by an enzyme called as nicotinamidase/pyrazinamidase which is encoded by gene pncA by mycobacterium into pyrazinoic acid. PYZ passively diffuse into the cell and converted into POA and this POA then went out by efflux pump into acidic extracellular environment where it combines with Hydrogen ion to form protonated form of acid. This protonated form POAH or HPOA has high lipid solubility due to which it diffuse back to cell and cause acidic environment by dissociating itself into Hydrogen ion and POA. this can further lead to either inhibition of fatty acid synthesis type 1 which further cause inhibition of mycolic acid, or it can cause the reduction of pH in the cell or disruption in the transportation system of Cell membrane. Pyrazinamide shows its action only in acidic extracellular environment. Resistance is caused by mutation in gene pncA which decreases the affinity of enzyme for pyrazinamide. single point mutation can lead to 70% resistant clinical isolates. Pharmacokinetics;90% bioavailibility orally and well distributed and cross BBB when meninges are inflamed. Half life of 8-11 hours. parent drug is metabolized by liver and metabolites are renally cleared. Clinically it is used in 25mg/kg/d. it is sterilizing agent as it kills intracellular organisms which are residing inside cells. and thus pyrazinamide decrease the relapse and resistance. it also reduces the treatment course to 6 months.Adverse effects are that it can cause liver damage when taken 45-50mg/kg in 15%of patients, jaundice, nausea, vomiting, drug fever, photosensitivity and hyperuricemia are some other adverse effects. In pregnancy it should be avoided as there is no such data against its teratogenicity. it has no known antidote yet. References: Goodman & Gilman's The Pharmacological Basis of Therapeutics Basic And Clinical Pharmacology by Bertram G. Katzung #Pyrazinamide #Mycobacteriumtuberculosis #PyrazinoicAcid