Propranolol Interactions

St. John's Wort potently induces CYP1A2 and CYP2C19 along with CYP3A4 and P-glycoprotein, accelerating the metabolism of propranolol and reducing its plasma levels. Documented cases include loss of intraocular pressure control in glaucoma patients on topical beta-blockers, and the mechanism predicts similar loss of antihypertensive and antiarrhythmic effect with systemic propranolol.

Propranolol blocks pineal beta-1 adrenergic receptors that control endogenous melatonin synthesis, suppressing nighttime melatonin levels by roughly 50% and contributing to insomnia, vivid dreams, and reduced sleep efficiency. Low-dose oral melatonin at bedtime can restore sleep architecture without compromising propranolol's antihypertensive effect.

Alcohol and propranolol can produce additive hypotension, dizziness, and sedation through combined vasodilation and central nervous system depression; propranolol also masks the warning symptoms of low blood sugar and rapid heart rate. Chronic heavy drinking induces hepatic enzymes and can reduce propranolol effectiveness.

Cigarette smoking induces hepatic metabolism of propranolol via CYP1A2 and accelerated glucuronidation, increasing apparent oral clearance and reducing propranolol plasma concentrations in smokers compared with non-smokers. Nicotine also independently raises heart rate, blood pressure, and circulating catecholamines, partially counteracting propranolol's beta-blocking effect.

Caffeine in coffee acutely raises heart rate and blood pressure, which can counteract the heart-rate and blood-pressure-lowering effects of propranolol, a non-selective beta-blocker. Propranolol may also slow caffeine clearance modestly, increasing caffeine exposure.

Piperine, the active alkaloid in black pepper, inhibits CYP3A4, CYP2C9, and intestinal P-glycoprotein, increasing the oral bioavailability and serum concentration of propranolol and other beta-blockers, which can amplify blood pressure and heart rate reduction.

Caffeine raises systemic vascular resistance and heart rate, partially opposing propranolol's blood-pressure and heart-rate lowering effects. High caffeine intake can also worsen tremor and anxiety that propranolol is prescribed to treat.