The pharmacodynamics of propranolol were studied in 12 cirrhotic Malay patients. Fifteen healthy Malay volunteers were selected and several clinical parameters were obtained. The effects of three doses of propranolol in reducing the heart rate (HR) of these patients were observed to be significantly different. These differences were seen at dosing of 10 mg vs 20 mg and 10 mg vs 30 mg (P<0.001 and P<0.01, respectively). However, no significant difference was seen for doses between 20 mg vs 30 mg. At 20 mg the reduction in HR is more pronounced than the effect seen with the other two doses. The effects of propranolol in reducing V(max) and V(mean) of portal vein blood flow were found to be not significant at doses of 10 mg vs 30 mg, but between 10 mg vs 20 mg and 20 mg vs 30 mg there was significant difference (P<0.05 and P<0.01, respectively). Reduction of V(max) of more than 10% of baseline was achieved at doses of 10 mg and 20 mg. However, at a dose of 20 mg a more significant reduction was observed than at a dose of 10 mg. Dose-concentration-effect relationship was seen to be significantly different between HR reduction and propranolol concentration of the three steady-state levels (P<0.001). Similar results were obtained with V(max) and V(mean). The V(max) was found to be a reliable parameter for the assessment of therapeutic effect of the drugs in conferring changes in portal haemodynamics of liver cirrhotic patients. Further, Child-Pugh score is thought to be an important supporting factor in evaluating prognosis. The results of this pharmacodynamics studies suggest that the optimal dose of propranolol may be 20 mg propranolol thrice daily for cirrhotic Malay patients.
Keywords: pharmacodynamics; portal hypertension; post-hepatitic cirrhosis; propranolol.