Pharmacology of combined alpha-beta-blockade. II. Haemodynamic effects of labetalol.
The cardinal haemodynamic disturbance in established hypertension is an increased total peripheral resistance and a subnormal blood flow, particularly during exercise. The spontaneously occurring changes in central haemodynamics have been followed in young males with essential hypertension over a 17-year period: a gradual increase in total peripheral resistance and blood pressure, and a gradual fall in cardiac output and stroke volume, have been demonstrated. Labetalol is a unique antihypertensive agent which induces both alpha- and beta-blockade. Numerous studies have shown that when labetalol is given intravenously to patients with mild to moderate essential hypertension, blood pressure falls within a few minutes-partly due to reduction in cardiac output and heart rate and partly due to reduction in total peripheral resistance. In most series the average reduction in blood pressure was 17 to 22%, the reduction in total peripheral resistance 11 to 14%, and the reduction in cardiac output 2 to 10%. Thus, the reduction in cardiac output with labetalol is less than that seen after single-dose injection of beta-blockers without intrinsic sympathomimetic activity. After intravenous injection, the blood pressure-lowering effect is most marked in the upright position and during muscular exercise when cardiac output is usually significantly reduced. Labetalol reduces blood pressure in severe hypertension. Intravenous doses of 0.2 to 0.8 mg/kg bodyweight reduce blood pressure by approximately 20%. This hypotensive effect is partly due to a reduction in total peripheral resistance and partly due to a fall in cardiac index. When the reduction in blood pressure is gradual and moderate (less than 20%), it is mainly produced by a reduction in total peripheral resistance. During long term use labetalol induces haemodynamic changes rather similar to those seen after bolus injection. However, during prolonged use there is a tendency to normalisation in cardiac output and stroke volume; the sustained decrease in blood pressure is mainly due to a reduction in total peripheral resistance. In a recent 6-year follow-up study where 15 patients were studied before treatment and after 1 and 6 years on long term labetalol treatment, a tendency to normalisation of central haemodynamics was found. Over the years total peripheral resistance was gradually reduced by 15 to 20% at rest as well as during exercise. Stroke volume gradually increased and after 6 years of treatment was approximately 10% higher than the pretreatment value. This compensated for the reduced heart rate and no significant reduction in cardiac output was seen either during exercise or at rest.(ABSTRACT TRUNCATED AT 400 WORDS)
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D007275:Injections, Intravenous; D007741:Labetalol / Q000494:pharmacology* / Q000627:therapeutic use; D005082:Physical Exertion / Q000187:drug effects; D011187:Posture; D011247:Pregnancy; D011652:Pulmonary Circulation; D012079:Renal Circulation / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D004983:Ethanolamines; D007741:Labetalol