Drug Interactions between Cosopt PF and Raplon

MONITOR: Neuromuscular blocking agents and beta-blockers may have additive cardiovascular depressant effects. In one study, 8 of 42 patients receiving beta-blockers developed bradycardia (less than 50 bpm) and hypotension (systolic BP less than 80 mmHg) when atracurium was administered. Most of these patients were under general anesthesia using diazepam, methohexital, droperidol, fentanyl, and nitrous oxide/oxygen. In isolated case reports, patients treated with timolol eye drops have developed bradycardia and hypotension when atracurium or alcuronium was administered. The interaction has also been reported with atenolol and atracurium.

MONITOR: Limited data suggest that beta-blockers may modestly potentiate the pharmacologic effects of neuromuscular blocking agents. The exact mechanism of interaction is unknown but may involve effects in the postsynaptic membrane, as beta-blockers alone have been reported to exacerbate or unmask myasthenia gravis. In one case report, two thyrotoxic patients treated with propranolol 120 mg/day for 14 days prior to surgery demonstrated prolonged neuromuscular blockade with tubocurarine. Likewise, eight study subjects receiving esmolol (300 to 500 mcg/kg/min) five minutes before induction of anesthesia experienced an approximately 3-minute delay in recovery from succinycholine-induced neuromuscular blockade relative to subjects receiving a placebo infusion. Other studies have not corroborated these findings. A study of 16 patients receiving chronic therapy (at least one month) with various beta-blockers found no significant difference in the onset and duration of action of rocuronium compared to 27 patients in the control group. Earlier studies even found a slight reduction in the effect of succinylcholine in patients treated with propranolol intravenously before surgery and a shorter duration of action of tubocurarine in patients administered propranolol or oxprenolol. Esmolol has been reported to delay the onset of action of rocuronium from 93 to 118 seconds.

MANAGEMENT: Clinicians should recognize the potential for altered effects of neuromuscular blocking agents in the presence of beta-blockers. Respiratory and cardiovascular status should be closely monitored.

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