Alcohol Withdrawal Changes Cardiovascular Responses to Propranolol Challenge

Abstract

The cardiovascular effects and plasma concentrations of a single dose of propranolol (80 mg) were studied non-invasively in alcohol-dependent subjects during alcohol withdrawal (AW) on day 1 and after resolution of withdrawal symptoms on day 10. At the onset of AW, propranolol caused a bradycardic effect which was significantly weakened on day 10. This might result from an increased bioavailability of propranolol on day 1 and from marked sympathetic activity. Propranolol also produced a negative inotropic effect, relatively weaker on day 1 than on day 10, being associated with increased β-receptor sensitivity towards the final phase of AW. These results suggest that peripheral and central β-adrenergic systems modulate the cardiovascular system in AW.

Cardiovascular effects of propranolol in patients with alcohol dependence during withdrawal

“…This study confirmed recent findings of Kähkönen (2003) in which the bradycardiac effect of propranolol weakened toward the end of WS. However, in the same study, the effects of propranolol on the negative inotropic effect were opposite: a relatively weaker effect was observed at the beginning of WS.…”

“…Total concentrations of propranolol were higher during withdrawal than after resolution of the withdrawal symptoms (Kähkönen, 2003), but concentrations of unbound fraction of propranolol were opposite (Sandor et al, 1983).…”

“…We developed a multivariate model for analyzing the effects of relevant dependent variables on drug response. For analysis, we also included data from the previous study (n = 6; Kähkönen, 2003). Procedures were exactly the same, but the dose of propranolol was 80 mg and patients were studied on days 1 and 10.…”

“…The β-adrenergic receptor antagonists timolol and propranolol are shown to lower heart rate and hypertension during WS (Sellers et al, 1977;Wormer, 1994), suggesting that changes in β-adrenergic function may underlie these cardiovascular abnormalities. Recently, Kähkönen (2003) showed that the cardiovascular effects of propranolol differ during withdrawal from those after 10 days of withdrawal. Although at that time patients showed no overt withdrawal symptoms, "hidden" cardiovascular abnormalities such as exaggerated cardiovascular reactivity revealed by functional tests may have been present (King et al, 1996).…”

Altered Cardiovascular Responses to Nitrosorbide in Alcohol Withdrawal

“…AW-related changes in adrenergic function have been shown to modulate cardiovascular responses in AW [9]. The hormones of the hypothalamus-hypophysis-adrenalaxis may also play a role.…”