Drug interactions between epinephrine/lidocaine and Inderide

propranolol ↔ epinephrine

Applies to:Inderide (hydrochlorothiazide/propranolol) and epinephrine/lidocaine

MONITOR CLOSELY: Noncardioselective beta-blockers can significantly enhance the pressor response to epinephrine. The mechanism involves blockade of beta-2 adrenergic receptors in the peripheral vasculature, resulting in unopposed alpha-adrenergic effect of epinephrine that is responsible for vasoconstriction. Severe hypertension accompanied by bradycardia has been reported in patients who were treated with a noncardioselective beta-blocker like propranolol or nadolol prior to receiving epinephrine. In rare cases, cardiac arrest and stroke have occurred. This interaction has not been reported with cardioselective beta-blockers, which generally have little effect on beta-2 adrenergic receptors at therapeutic dosages. In studies of hypertensive patients, treatment with propranolol was associated with significant increases in blood pressure and peripheral vascular resistance and decreases in heart rate and forearm blood flow in response to epinephrine administration, while metoprolol had only minor effects on epinephrine-induced cardiovascular changes compared to placebo. Similarly, in 24 healthy subjects treated with nadolol, atenolol, or placebo for one week prior to epinephrine administration, mean arterial pressure and calf vascular resistance increased significantly in the nadolol group but not in the atenolol group, and marked bradycardia also occurred in the former but not latter group. Theoretically, the interaction may also occur with noncardioselective beta-blocker ophthalmic preparations, since they may be systemically absorbed and can produce clinically significant systemic effects even at low or undetectable plasma levels.

MONITOR CLOSELY: Beta-blockers may attenuate the response to epinephrine in the treatment of anaphylactic reactions. Noncardioselective beta-blockers, in particular, can antagonize the bronchodilating effects of epinephrine by blocking beta-2 adrenergic receptors in smooth muscles of the bronchial tree. All beta-blockers can antagonize the cardiostimulatory effects of epinephrine by blocking beta-1 adrenergic receptors in the heart. Some investigators have suggested that the use of beta-blockers in itself is associated with an increased incidence and severity of anaphylaxis due to modulation of adenylate cyclase, which can influence release of anaphylactogenic mediators. However, data are limited and conflicting.

MANAGEMENT: Extreme caution and close monitoring of cardiovascular status are indicated when epinephrine is administered to patients treated with noncardioselective beta-blockers. A dosage reduction of epinephrine may be necessary. Withdrawal of beta-blockers before anesthesia may increase the risk of myocardial ischemia and is not recommended. The interaction is not expected to occur with local anesthetics used in dental surgery that contain very low concentrations of adrenaline (epinephrine).

propranolol ↔ lidocaine

Applies to:Inderide (hydrochlorothiazide/propranolol) and epinephrine/lidocaine

MONITOR: Some beta-blockers may increase lidocaine levels and risk of toxicity. The proposed mechanism is enzyme inhibition and/or decreased cardiac output and hepatic blood flow resulting in decreased hepatic metabolism of lidocaine. In addition beta-blockers and lidocaine may also have additive negative inotropic effects on the heart. Data have been conflicting and variable.

MANAGEMENT: Patients receiving concurrent therapy should be monitored for drowsiness, mental status changes, bradycardia, and hypotension. Lidocaine levels should be obtained when clinically necessary. If toxicity is suspected, the lidocaine infusion should be decreased, as possible.