Propranolol-Withdrawal Rebound Phenomenon

Abstract

Effects on anginal symptoms of sudden withdrawal of large doses of propranolol or placebo were evaluated in 20 patients in a double-blind crossover efficacy trial requiring sudden cessation of the agent. With propranolol, 160 to 320 mg per day for six and 12 weeks, no patients had increased angina or nitroglycerin use, and there were no hospitalizations or deaths. However, within two weeks of discontinuance of propranolol, untoward ischemic events developed in 10 patients. Six had serious withdrawal complications: intermediate coronary syndrome in three, and ventricular tachycardia, fatal myocardial infarction, and sudden death in one each. In four patients discontinuance of placebo increased anginal symptoms; in the remaining 10, ischemic symptoms were not provoked. The rebound phenomenon was related to degree of pre-propranolol angina and relief of pain by the agent. Thus, chronically administered propranolol should be gradually reduced, and activity restricted during its withdrawal.

Chronic Administration of KB-R7943 Induces Up-regulation of Cardiac NCX1

“…Furthermore, it has long been understood that inhibition of ␤-adrenergic receptor activity leads to increases in the density of ␤-adrenergic receptors present in the cell (29). Interestingly, the withdrawal of ␤-blockers has been found to greatly increase the risk of unstable angina, myocardial infarction, and sudden death (46,47). Because NCX1 plays a crucial role in calcium handling in the cardiomyocyte, it is an adaptive response of the cell to attempt to counteract diminished exchanger activity by increasing exchanger expression.…”

Antipsychotic-Induced Dopamine Supersensitivity Psychosis: Pharmacology, Criteria, and Therapy

“…Several CNS drug rebound syndromes have been reported to occur following drug discontinuation after short-term use: REM rebound with barbiturates and non-benzodiazepine hypnotics [106,107]; rebound myocardial angina and infarction with propranolol [108]; rebound insomnia [105], rebound anxiety [103], and rebound panic [109], with benzodiazepines with short and intermediate t 1/2 (triazolam, lorazepam, and alprazolam); and rebound depression [1,41]. …”

“…Early recognition of postwithdrawal disorders for a given class of drugs is facilitated by the presence of high-potency drugs combined with short t 1/2 [1,123,124]. Due to the short duration of action, there is a rapid decrease in occupancy of receptors produced in greater number by potent blocking drugs, thus resulting in a greater number of receptors in their unblocked state [1,108,123,124]; this was the case for β-adrenergic blocking drugs. As early as 1975, dose was highlighted as an additional factor for early recognition of postwithdrawal disorder; 160-320 mg propranolol/day would produce an adrenergic rebound unmasked rapidly by discontinuation, which led to an increase in cardiac contractibility, heart rate, myocardial ischemia, and rapid death, even after short-term use (6-12 weeks) [108].…”

“…Due to the short duration of action, there is a rapid decrease in occupancy of receptors produced in greater number by potent blocking drugs, thus resulting in a greater number of receptors in their unblocked state [1,108,123,124]; this was the case for β-adrenergic blocking drugs. As early as 1975, dose was highlighted as an additional factor for early recognition of postwithdrawal disorder; 160-320 mg propranolol/day would produce an adrenergic rebound unmasked rapidly by discontinuation, which led to an increase in cardiac contractibility, heart rate, myocardial ischemia, and rapid death, even after short-term use (6-12 weeks) [108]. Interestingly, in this first report of adrenergic rebound, major complications such as death were seen in patients who responded better to propranolol [108], which is also a characteristic of SP, most often seen in good antipsychotic drug responders [14,72].…”

Medication management on sick days

“…Acute coronary syndrome has also been reported, even in patients without coronary artery disease. 16,17 The risk of these events appears to be inversely related to the drug's half-life and the extent of receptor downregulation.…”