Dose‐response curves for heart rate, cardiac output, arterial blood pressure, and pulmonary artery pressure were obtained in 37 patients with ischemic heart disease after intravenous administration of six increasing doses of propranolol, atenolol, practolol, pindolol, CPEP (1 ‐[2‐cyanophenoxy]‐3β‐[3‐phenylureido]‐ethylamino‐2‐propanol), and BMMP (1‐t‐butylamino‐3‐[2‐N‐methylcarbamoyl‐methoxyphenoxy]propan‐2‐ol‐hydrochloride). The doses were equipotent, as indicated by reduction in exercise‐induced tachycardia. The dose‐response curves for cardiac output and heart rate can be divided into three groups according to the degree of intrinsic sympathomimetic activity. One group without intrinsic sympathomimetic activity included propranolol and atenolol, which reduced cardiac output (about 26% to 28%) and heart rate (about 15% to 17%). A second group with moderate intrinsic sympathomimetic activity, represented by practolol and BMMP, induced less reduction in cardiac output (about 12% to 17%) and heart rate (about 7% to 10%). A third group with pronounced intrinsic sympathomimetic activity, represented by pindolol and CPEP, did not reduce cardiac output and heart rate. Mean systemic blood pressure was essentially unchanged even after the largest dose of any of the drugs. Mean pulmonary artery pressure rose after atenolol, propranolol, and BMMP but not after pindolol, CPEP, and practolol. Atenolol, BMMP, and practolol are beta‐1–selective drugs, it is concluded that the acute hemodynamic response to adrenergic beta receptor blocking drugs at rest is determined primarily by the degree of intrinsic sympathomimetic activity, whereas beta‐1 selectivity did not modify the central hemodynamic responses to beta adrenoceptor blockade. Clinical Pharmacology and Therapeutics (1981) 29, 711–718; doi:

Emergency treatment of acute, severe hypertension defined as diastolic blood pressure (DBP) ≥ 135 mmHg combined with cerebral symptoms was prospectively monitored in a randomized multicenter study including 64 patients. Treatment was divided into two periods. In the first hour the patients were observed in the supine position after being given 40 mg furosemide intravenously. If DBP remained >125 mmHg (n=52), the patients were put on fractionated diazoxide administered intravenously (n=28) or dihydralazine administered intramuscularly (n=24). Blood pressure (BP) decreased with diazoxide from an average of 241/149 mmHg to 180/111 mmHg after 5 hours and with dihydralazine from 237/149 to 161/101 mmHg. The inter‐individual BP response varied considerably. A clear and identical regression in neurological symptoms was observed on both drug regimens. No new neurological symptoms were seen to develop. It is concluded that a gradual fall in BP can be obtained after fractionated dosage of diazoxide (i.v.) as well as after dihydralazine (i.m.). The indication of acute parenteral therapy compared to less aggressive oral treatment is discussed.

In a population study on the western coast of Greenland the incidence of sucrose malabsorption was estimated by means of sucrose tolerance tests in 190 persons. Smallintestinal disaccharidase activity was estimated in 19 patients. Sucrose malabsorption was present in 10-5°o of the cases studied-a surprisingly high figure and much higher than the incidence reported elsewhere in the world. This incidence is, however, lower than that of lactose malabsorption in Greenland Eskimos (54%). In contrast to lactose malabsorption, sucrose malabsorption is present from birth; this may have important clinical implications since chronic diarrhoea and malnutrition are fairly common during infancy in Greenland.

In a double-blind, randomized, crossover study, the effects of intravenous pinacidil, 0.2 mg/kg, were compared with those of hydralazine, 0.3 mg/kg, before and after beta-adrenoceptor blockade in six subjects with hypertension. Both drugs equally reduced total peripheral resistance by about 40%. Pinacidil reduced mean blood pressure by an average of 30 mm Hg, while the reduction after hydralazine was 10 mm Hg. The difference in antihypertensive effect resulted from greater increases in heart rate, cardiac contractility (systolic time intervals), and cardiac index (thermodilution) after hydralazine. These effects after hydralazine could not be fully abolished by beta-blockade, as could the effects after pinacidil. Pinacidil decreased pulmonary blood pressure, whereas there was a slight rise in pulmonary blood pressure after hydralazine. Forearm blood flow (venous occlusion strain gauge plethysmography) increased equally after both drugs; thus pinacidil decreased forearm vascular resistance more than hydralazine did. Serum concentrations of both drugs were within the therapeutic range and correlated with the fall in mean blood pressure. Five subjects complained of side effects after hydralazine, but none were reported after pinacidil. Hydralazine increased myocardial oxygen consumption (as estimated from the rate-pressure product) by 35%; there was no change after pinacidil. It is suggested that hydralazine has direct cardiostimulatory effects that limit its antihypertensive effectiveness. These effects increase myocardial oxygen consumption and may be responsible for the common and sometimes severe cardiovascular side effects of hydralazine.