5 (Student Presentation) - Anti tuberculosis: Pyrazinamide

Question 1

MoA of Pyrazinamide

Answer 1

PZA –> converted by PZase –> POA

In M. tuberculosis, Influx HPOA > Efflux POA –> Cytosol acidification –> membrane function disruption

Question 2

PK of Pyrazinamide

Answer 2

Absorption: Rapid through GI tract; reduced bioavailability when taken with a high-fat meal

Distribution: 10% bound to plasma proteins; widely distributed throughout body tissues, fluids, and CSF

Metabolism: Undergo oxidation in the liver to become 5-hydroxypyrazinamide

Excretion: Oral drug (70% metabolites, 4% unchanged drug excreted in the urine)

Question 3

Common side effects of Pyrazinamide

Answer 3

Hepatoxicity, Hyperuricemia, and Arthralgia

Question 4

Side effect management of Pyranizamide

Answer 4

Hepatoxicity –> Withdrawal if liver injury detected

Hyperuricemia –> Asymptomatic (no significant treatment), Gout Formation (Take NSAIDs for acute condition or urate-lowering drugs for recurrent gout + monitoring of uric acid level and hydration)

Arthralgia and Myalgia –> Take aspirin