Withdrawal phenomena after atenolol and bopindolol: hormonal changes in normal volunteers.

Abstract

1. In order to observe and compare the withdrawal phenomena which follow treatment with the beta‐adrenoceptor blocking drugs, bopindolol (with partial agonist activity PAA) and atenolol (without PAA), two groups of six normal volunteers were studied before, during and after 16 days drug administration. 2. Measurements of plasma levels of cortisol, prolactin, insulin, noradrenaline, adrenaline, glucose and potassium were made during a pre‐treatment baseline period, on maximum dose and for 21 days after drug withdrawal. Isoprenaline infusions were given to determine sensitivity of heart rate responses and haemodynamic changes measured in response to physiological manoeuvres. 3. Following atenolol withdrawal the results show hormonal evidence of adrenergic overactivity in the form of elevation of plasma cortisol, insulin and glucose levels. After bopindolol withdrawal there was, in contrast, an overshoot of plasma prolactin and a persistent elevation of plasma potassium and adrenaline post‐isoprenaline. 4. The hormonal changes which follow withdrawal of atenolol and bopindolol are associated with haemodynamic changes reported elsewhere (Walden et al., 1990). 5. These observations provide confirmatory evidence of a post beta‐adrenoceptor blockade withdrawal syndrome which differs between the two drugs studied and this may reflect the properties of the drugs, in particular the PAA of bopindolol.

Effect of pindolol on hormone secretion and body temperature: Partial agonist effects

“…This is in accord with the majority of studies with beta blockers (Walden et al, 1990). However, it has been reported that atenolol, a beta blocker, without appreciable 5-HT~A affinity, slightly increases plasma cortisol secretion (Walden et al, 1990). Thus, we cannot rule out that the pindolol-induced cortisol stimulation is due, in part, to beta-adrenoceptor antagonism.…”

“…Lesch et al (1990b,c) have reported that beta-adrenergic blockers which lack affinity for 5-HTza receptors do not increase plasma cortisol levels or decrease body temperature in man. This is in accord with the majority of studies with beta blockers (Walden et al, 1990). However, it has been reported that atenolol, a beta blocker, without appreciable 5-HT~A affinity, slightly increases plasma cortisol secretion (Walden et al, 1990).…”

Withdrawal phenomena after atenolol and bopindolol: haemodynamic responses in healthy volunteers.

“…In the present study we have extended observations of withdrawal phenomena made previously to include more pre-treatment baseline observations and a longer period of observation during the withdrawal phase. In addition, we have measured various hormone levels before and during the withdrawal phase; this is reported elsewhere (Walden et al, 1990). The two drugs chosen for this study were atenolol, a 131-adrenoceptor-selective drug without any PAA and bopindolol, a long acting non-selective drug with moderate PAA.…”

“…4 Some subjects showed clear evidence of overshoot of HR and BP on exercise demonstrating that certain individuals may be more prone to have withdrawal effects than others.5 The length of time during which withdrawal phenomena can occur is probably longer than has previously been realised. 6 Hormonal changes were found in the withdrawal period (Walden et al, 1990).…”

“…5 The length of time during which withdrawal phenomena can occur is probably longer than has previously been realised. 6 Hormonal changes were found in the withdrawal period (Walden et al, 1990).…”