Kajian farmakodinamik i kesan pelbagai tingkat dos propranolol terhadap beberapa parameter klinikal dan farmakokinetik dos terpilih pada pesakit sirosis hepar dikalangan populasi Melayu

Abstract
Pharmacodynamic of different doses of propranolol on several clinical parameters for controlling variceal bleeding has been studied in 12 liver cirrhotic Malay patients at steady-state levels (1 0 male and 2 female). Eleven of them were posthepatitis B cirrhosis and another one was biliary cirrhosis. There has been no properly conducted research done in pharmacodynamics and pharmacokinetics of propranolol in .. cirrhotic Malay patients. Regimeruof three doses of propranolol were 10 mg, 20 mg and 30 mg peroral thrice a day. The effects of three doses of propranolol on reducing heart rate (HR) were significantly different between 10 mg vs 20 mg and 10 mg vs 30 mg (P < 0.001 and P < 0.01), respectively, but between 20 mg vs 30 mg doses, there were no significant difference. The 20 mg was able to reduce HR maximally. On the other hand, the propranolol effects on reducing V max and V mean of portal vein, there were significant difference between 10 mg vs 20 mg and 20 mg vs 30 mg (P < 0.05 and P < 0.01 ), respectively, but between 10 mg vs 30 mg, there were no significant difference. Reduction of V max more than 10% of baseline were achieved by I 0 mg and 20 mg, however, 20 mg caused more reduction than 10 mg. The pharmacodynamic studies of different clinical parameters showed that among the doses tested, 20 mg x 3/day (60 mg/day) was the most appropriate dose for the cirrhotic Malay patients. It was observed that this dose was the optimal dose required to reduce maximum blood flow velocity in the portal vein of these patients. This dose was much smaller than the dose used in Caucasians suffering from the same disease (80-320 mg/day). It has been mentioned that V max was a reliable criterion to evaluate the efficacy of the drugs which are capable of decreasing the velocity of blood flow in the portal vein. In our study, there was no correlation between a decline in pulse rate and a decrease in V max, in propranolol users. Therefore, this indicated that reduction in pulse rate was not a reliable parameter to elucidate the blood flow in the portal vein. Consequently, the chosen dose of 20 mg x 3/day propranolol in cirrhotic Malay patients was ยท used irrespective of the ability to reduce the HR. Pharmacodynamic
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Keywords
Farmakokinetik dos , Sirosis hepar
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