Depressed melatonin secretion in patients with nightmares due to beta-adrenoceptor blocking drugs.

Nocturnal urinary melatonin excretion was evaluated in six patients with nightmares and hallucinations during treatment with beta-adrenoceptor blocking agents, and compared to six control patients with similar diagnoses and treatment but without such symptoms from the central nervous system (CNS). Nightly melatonin excretion was lower in all cases with nightly CNS-symptoms than in the control patients. The results also suggest drug differences and dose dependency. It is concluded that in predisposed patients CNS side-effects induced by beta-adrenoceptor antagonists are related to depressed nightly melatonin secretion.

beta-adrenergic blockade and diabetes mellitus. A review.

The use of beta-blockers in diabetes mellitus has largely been restricted because of the reported adverse effects. Clinical investigations aimed at elucidating the possible reactions associated with the use of beta-blockers have disclosed no evidence of masking or signs or insulin-induced hypoglycaemia or potentiation of the insulin effect. Prolonged hypoglycaemia may develop, however, as a result of physical effort. There is no proof that during insulin-induced hypoglycaemia the concentrations of counter-regulatory hormones are depressed, but that of glycerol, a gluconeogenic precursor, is slightly diminished. Intensification of the hypertensive reaction during hypoglycaemia is less likely to occur during treatment with beta-selective blockers. In insulin-dependent diabetics receiving beta 1-blockers there is no evidence of any change - either deterioration or improvement - in metabolic control. In one small controlled trial there was no sign of impairment of the peripheral arterial circulation over a short period of administration of a non-selective beta-blocker. In general, for patients suffering from insulin-dependent diabetes, cardioselective agents are preferable. Since cardioselectivity is a dose-dependent property, reasonable caution should also be observed when using this type of drug in diabetes.

Established beta-adrenergic receptor blocking therapy and acute myocardial infarction. A clinical study of risks and benefits.

In order to evaluate the risks and benefits of continuing established therapy with beta-adrenergic receptor blocking drugs during acute myocardial infarction (AMI), 183 consecutive patients, 63 with (beta-blocker group) and 120 without (control group) this therapy, were studied. Detailed information on previous diseases, present symptoms, established medication, clinical and laboratory findings on admission and during the first 12 hours in the CCU was collected. The incidences of congestive heart failure, hypotension, AV blocks and ventricular arrhythmias were not significantly more common in the control group (8 vs. 28%, p less than 0.01). Thus, continuation of established therapy with beta-adrenergic receptor blocking drugs does not seem to increase the risk of complications after hospital admission for AMI. The reason for the low incidence of inferior wall infarction in the beta-blocker group is not clear but it cannot be excluded that when patients on beta-adrenergic receptor blocking therapy develop an inferior AMI, they may run a greater risk of sudden death.

Alprenolol-induced thrombocytopenia.

A case of alprenolol-induced thrombocytopenia in a 65-year-old woman is reported. She was admitted to the hospital twice with platelet counts below 10X10(9)/l. The platelet count rapidly returned to normal after discontinuation of alprenolol. The reason for the thrombocytopenia was increased platelet destruction.

Vasospastic phenomena in patients treated with beta-adrenoceptor blocking agents.

Twenty-one patients developed Raynaud's phenomenon during treatment with beta-adrenoceptor blocking agents. The vasospastic symptoms were obviously related to the treatment, but their pathogenesis is still controversial. A decrease in cardiac output might explain the phenomenon. According to our very preliminary data an alpha-adrenergic dominance caused by a direct effect on the peripheral circulation seems more probable. Vasospastic symptoms may arise after treatment with both cardioselective and non-selective beta blocking agents. Cautious prescription of beta blocking drugs to patients with preexisting peripheral vascular disease is recommended.

Long-term clinical experience with atenolol--a new selective beta-1-blocker with few side-effects from the central nervous system.

During the last four years we have used a new cardioselective beta-adrenergic blocking substance, ICI 66.082 (atenolol or Tenormin), alone or in combination with other drugs for treatment of hypertension in a total of 104 patients, including 15 with a chronic obstructive lung disease. Fifty-one patients started treatment with atenolol because of side-effects--especially from the central nervous system--during previous treatment with non-selective beta-blockers, mostly propranolol (Inderal). Mean duration of treatment was 16 months (range 8--36) and mean dosage 163 mg/day. In 18 patients treatment with Tenormin was withdrawn, but only in 10 of them could this be referred to side-effects. Of the 51 patients who complained of or showed side-effects from another beta-blocker, 80% were improved after changing to Tenormin. Of the patients with side-effects from the central nervous system, 73% improved, especially those who complained of nightmares, hallucinations, insomnia or mild depression.

Placebo-controlled, double-blind clinical trial of alprenolol in African hypertensive patients.

A placebo-controlled, double-blind clinical trial of alprenolol was carried out in 20 hypertensive Africans. The active drug and placebo were each administered for 8 weeks using a crossover design. Alprenolol was given in the form of a slow-release tablet preparation at a dosage of 200 mg twice daily. Four patients were withdrawn from the study either because of side-effects (2 patients) or non-compliance (2 patients). The mean reduction in blood pressure obtained in the 16 patients who completed the trial was less than that usually reported in Caucasians.

Contact eczema produced by a beta-adrenergic blocking agent (alprenolol).

In a pharmaceutical industry, several cases of allergic contact eczema caused by the beta-adrenergic blocking agent alprenolol (Aptin) have appeared. This report deals with 12 men and two women who developed eczema during work with the substance. In 13 of the 14 cases, the induction time for sensitization was less than 1 year. The skin reactions were very florid. After healing they could be reproduced by very small quantities of the substance. In one case, eczema could also be produced after ingestion of Aptin tablets. All the cases were transferred to other work within the factory. An intensive programme was implemented to remove dust from the working areas. Despite this, isolated new cases still appear. Some employees in contact with the substance also experienced mucous membrane symptoms. These symptoms could not be shown to have an allergic aetiology, but were considered to be irritant reactions. Alprenolol must be considered a very strong contact allergen.

Long-term treatment with beta-blockers after myocardial infarction.

162 patients discharged from hospital after mycardial infarction were randomly allocated to two groups, one received alprenolol 400 mg daily and the other served as the control. The period of follow-up was two years and all other treatment given was standardized. The two groups did not differ with respect to risk factors for myocardial infarction, the course of the acute infarct or treatment during follow-up. After two years one patient in the group treated with alprenolol had died suddenly as compared to nine in the control group. During the same period four fresh infarcts had occurred in the alprenolol group compared to 15 in the control group. Both these differences were statistically significant. Only four patients were obliged to discontinue beta-blocker treatment because of suspected side-effects. Long-term post-infarction treatment with beta-blockers appears to be an effective form of secondary therapy without serious side-effects.