Beta‐adrenoceptor blockade and hypoglycaemia. A randomised, double‐ blind, placebo controlled comparison of metoprolol CR, atenolol and propranolol LA in normal subjects.

Abstract

1. The effect of 1 week of treatment with propranolol LA (160 mg), atenolol (100 mg) and metoprolol CR (100 mg) on awareness of and the physiological responses to moderate hypoglycaemia were compared with placebo using a randomised, cross‐over design in 12 healthy volunteers. 2. All three beta‐adrenoceptor antagonists reduced resting heart rate, systolic blood pressure and heart rate responses to submaximal exercise compared with placebo. 3. Under hyperinsulinaemic (60 mu m‐2 min‐1) clamp conditions, at a blood glucose of 2.5 mmol l‐1, atenolol prevented the rise in systolic and atenolol and metoprolol CR prevented the fall in diastolic blood pressure usually associated with hypoglycaemia. At this level of hypoglycaemia, the expected increase in heart rate was inhibited by atenolol but not metoprolol CR. Pre‐ treatment with propranolol LA resulted in a significant pressor response and a bradycardia during hypoglycaemia. In addition the normal increase in finger tremor was abolished by propranolol LA. 4. During hypoglycaemia all three beta‐adrenoceptor blockers augmented sweating compared with placebo but hypoglycaemic symptoms, awareness and slowing of reaction time were the same with drugs and placebo. 5. The rise in plasma adrenaline and other counter‐regulatory hormones during hypoglycaemia was enhanced by beta‐adrenoceptor blockade. 6. We conclude that beta‐adrenoceptor antagonists modify the physiological and hormonal responses to, but do not adversely affect awareness of, moderate hypoglycaemia in healthy volunteers.

Potential drug-drug interactions in 5,125 mostly elderly out-patients in Gothenburg, Sweden

“…Hansten and Horn highlight 13-adrenergic blockers as a group without considering whether they are selective or non-selective. However, this DDI is of major clinical importance, especially for the non-selective 13-adrenergic blockers [20][21][22][23]. Of these 86 DDIs, only 12 were DDIs between nonselective 13-adrenergic blockers (propranolol, sotalol, alprenolol) and antidiabetics (insulin or oral antidiabetics).…”

Vascular disease and diabetes: is hypoglycaemia an aggravating factor?

“…This response is absent in tetraplegic patients who have a pre-synaptic sympathectomy caused by traumatic transection of the cervical cord [60], and it appears to be mediated via β 1 adrenoceptors [61]. The blood pressure changes are thought to be caused by epinephrine via α and β 2 adrenoceptors, and can be reproduced by infusing epinephrine intravenously [61]. Both myocardial contractility and cardiac output increase and peripheral vascular resistance declines [62].…”

“…By studying patients with autonomic deficits, the increment in heart rate has been found to be mediated via sympathetic activity. This response is absent in tetraplegic patients who have a pre-synaptic sympathectomy caused by traumatic transection of the cervical cord [60], and it appears to be mediated via β 1 adrenoceptors [61]. The blood pressure changes are thought to be caused by epinephrine via α and β 2 adrenoceptors, and can be reproduced by infusing epinephrine intravenously [61].…”

Effect of atenolol on QTc interval lengthening during hypoglycaemia in type 1 diabetes

“…Atenolol is widely used in type 1 diabetic patients, and its safety profile is well established following work refuting theoretical concerns regarding hypoglycaemia unawareness and delayed recovery from hypoglycaemia [12]. Unlike unselective beta-blockers, which may prolong recovery from hypoglycaemia [12,13], beta 1 -selective agents such as atenolol do not inhibit hypoglycaemia-induced glycogenolysis, and although some hypoglycaemic symptoms (e.g.…”

“…Unlike unselective beta-blockers, which may prolong recovery from hypoglycaemia [12,13], beta 1 -selective agents such as atenolol do not inhibit hypoglycaemia-induced glycogenolysis, and although some hypoglycaemic symptoms (e.g. tremor) are reduced, others, such as sweating, are increased [12].…”