40-årig man med essentiell hypertoni, tidigare (till mars 1980) behandlad med Apresolin. Nu Peripre

Fråga: 40-årig man med essentiell hypertoni, tidigare (till mars 1980) behandlad med Apresolin. Nu Peripress (1 1/2 mg x 3), Seloken (100 mg x 3), Salures K 1x1.

I somras (1981) hade patienten ASAT (0.83), ALAT (1.27). 15 september var gamma-GT 0.99 (no < 0.90) och ASAT (0.55), ALAT (0.87). 27/11 var ALAT 0.72, ASAT 0.55 och gamma-GT 1.33. ALP normala. Frågan är om dessa prover kan sättas i samband med medicineringen? Är med säkerhet ej alkoholmissbrukare.

Sammanfattning: There have been no case report of liver enzyme changes due to prazosin therapy for essential hypertension, nor were there similar documentations for metoprolol and bendroflumethiazide in the literature. However, rare instances of jaundice or serum aminotransferase changes attributed to the use of propranolol or chlorothiazide, respectively, have been observed. This case of hepatic complication during combined treatment with prazosin, metoprolol and bendroflumethiazide should be reported to Socialstyrelsens biverkningsnämnd.

Svar: This patient had liver function test changes, revealed as increase of serum aminotransferase and gamma-GT levels, during the combined treatment with prazosin, metoprolol and bendroflumethiazide. The question is whether these drugs or any one of them could be the cause of liver function changes?

As yet, there have been no case report of liver function changes directly attributed to the use of any of the three drugs (1-4). Hence, the thiazide diuretics, the beta-blocking agents or prazosin may be administered to patients with liver diseases. However, the relationship between them and liver damage may still be commented.

One wellknown fact is that excessive diureses with potassium depletion predisposes to hepatic precoma and coma (5,6). Besides, rare instances of jaundice have been observed during chlorothiazide therapy. The pattern of serum bilirubin, serum cholesterol, cephalin flocculation and serum glutamic oxalacetate transaminase changes (ASAT) and histologic findings were consistent with intracellular obstructive jaundice and the mechanism was considered to be hypersensitivity (7). Very rarely reported, the prototype beta-adrenoceptor blocking agent, propranolol, has produced mild increases in ASAT activity (8). Data about the effect either of metoprolol or of prazosin on serum aminotransferase and on gamma-GT are lacking (4,9). They are eliminated by hepatic metabolism (10,11). In addition, this patient have had hydrallazine therapy till March 1980. A recent report about hydrallazine-induced hepatitis has been published (12). This describes abnormal liver function tests after the hydrallazine therapy.

According to the record from 1965 to 1981 of Swedish National Board of Health, of 2965 cases of liver damage complications only one, three, one and thirteen were ascribed to bendroflumethiazide, metoprolol, prazosin and hydrallazine respectively. 1 Whitfield JB, Moss DW, Neale G, Orme M, Breckenridge A: Changes in plasma gamma-glutamyl transpeptidase activity associated with alterations in drug metabolism in man. Br Med J 1973; 1: 316-318 2 Zimmerman HJ, Hepatotoxicity, 1978, p. 518. Appleton-Century-Crofts, New York 3 Husserl FE, Messerli FH: Adverse effects of antihypertensive drugs. Drugs 1981; 22: 188-210 4 Brogden RN, Heel RC, Speight TM, Avery GS: Metoprolol: a review of its pharmacological properties and therapeutic efficacy in hypertension and angina pectoris. Drugs 1977; 14: 321-348 5 Sherlock S, Senewiratne B, Scott A, Walker JG: Complications of diuretics therapy in hepatic cirrhosis. Lancet 1966; I: 1049-1052 6 Goodman and Gilman, The pharmacological basis of therapeutics, 6th ed, 1980 7 Drerup AL, Alexaner WA, Lumb GD, Cummins AJ, Clark GM: Jaundice occurring in a patient treated with chlorothiazide. N Engl J Med 1958; 259: 534-536 8 Davies DM, Textbook of adverse drug reaction, 2nd ed, 1981, p. 368. Oxford University Press 9 Prazosin research group in Japan: Open studies with prazoscin in the treatment of essential hypertension. Med J Aust Spec Suppl 1977; 2: 38-41 10 Jaillon P: Clinical pharmacokinetics of prazosin. Clin Pharmacokinet 1980; 5: 365-376 11 Regårdh CG, Jordö L, Ervik M, Lundborg P, Olsson R, Rönn O: Pharmacokinetics of metoprolol in patients with hepatic cirrhosis. Clin Pharmacokinet 1981; 6: 375-388 12 Barnett DB, Hudson SA, Golightly PW: Hydrallazine-induced hepatitis? Br Med J 1980; 280: 1165-1166