Pyrazinamide (Zinamide(R)) is registered in several countries but not in Sweden. It is sometimes u

Fråga: "Pyrazinamide (Zinamide(R)) is registered in several countries but not in Sweden. It is sometimes used in Sweden in combination with other tuberculostatics, as a "licence drug". The doctor wants to use it in a patient with chronic liver disease caused probably both by excess of alcohol and being a sequalae of previous viral hepatitis.

Therapeutic effect in long term treatment?"

Sammanfattning: The aim of modern tuberculosis chemotherapy is not only to kill the actively multiplying bacilli but also to sterilize the lesions. Pyrazinamide exerts its maximum effect during the initial phase of therapy, due to the elimination of most of the intracellular bacterial population in the early stage of treatment.

Svar: Pyrazinamide is a synthetic pyrazine analog of nicotinamide. It is readily absorbed and widely distributed. Plasma elimination half-life is about 9-10 hours. Pyrazinamide is hydrolysed to pyrazinoic acid and subsequently hydroxylated to 5-hydroxypyrazinoic acid the major excretory product (1). About 30 per cent of the dose is excreted in urine as pyrazinoic acid and 4 per cent as unchanged pyrazinamide within 24 hours (2). It diffuses readily into the CSF.

The most common and serious side effect is hepatotoxicity. Hyperuricemia currently occurs as the renal secretion of uric acid is impaired, probably by the metabolite pyrazinoic acid. Other side effects are arthralgias, malaise, fever, sideroblastic anemia and dysuria (2). Gastrointestinal disturbances, photosensitization, blood coagulation and hematopoietic disorders have been reported (3).

Pyrazinamide is a bactericidal drug with sterilizing properties as it is active on slowly multiplying populations of bacilli, namely the "persisters". It has specific actiony at acidic pH. Such an environment is likely to be widespread in early acute inflammatory lesions and in macrophages (4).

When used alone, resistance may develop within 6 to 8 weeks (2). The addition of pyrazinamide to antitiberculous regimens in the initial phase of treatment (2 months) leads to more rapid conversion to negative cultures, prevents the emergence of resistance and decreases the relapse rate after the end of chemotherapy (4). 1 Goodman and Gilman, The pharmacological basis of therapeutics, 1985; 7th ed: 1207, 1215-1218

2 Martindale, The extra pharmacopoeia, 1982; 28th ed:
3 Meyler/herxheimer, Side effects of drugs, 1985; Annual 9: 270-271, 273
4 Dutt AK, Stead WW: Present chemotherapy for tuberculosis. J Infect Dis 1982; 146: 698-705

5 Girling DJ: The role of pyrazinamide in primary chemotherapy for pulmonary tuberculosis. Tubercle 1984; 65: 1-4