Drug Interactions between Combigan and tubocurarine

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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MONITOR: Topically administered alpha-2 adrenergic receptor agonists such as apraclonidine and brimonidine are systemically absorbed, with the potential for producing rare but clinically significant systemic effects such as hypotension and bradycardia. The possibility for an additive or potentiating effect on blood pressure and heart rate should be considered when used with other medications that affect these parameters, such as ophthalmic and systemic beta blockers, vasodilators, cardiac glycosides, and antihypertensive agents.

MANAGEMENT: Blood pressure and pulse rate should be monitored regularly when topical alpha-2 adrenergic receptor agonists are prescribed in combination with cardiovascular drugs. Patients should be advised to notify their physician if they experience slow pulse, irregular heartbeat, dizziness, lightheadedness, or syncope.

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