Cocaine may induce myocardial ischemia through various mechanisms, including coronary vasospasm, platelet aggregation within the coronary arteries, as well as rupture of an atherosclerotic plaque. At the molecular level, cocaine induces coronary vasospasm via inhibition of norepinephrine reuptake by presynaptic neurons. This enables increased binding of norepinephrine to alpha-1 adrenergic receptors within the smooth muscle of the coronary arteries, thereby inducing coronary vasospasm, leading to myocardial ischemia. It has long been postulated that the use of beta-blockers may exacerbate the vasospasm induced by cocaine due to an “unopposed alpha effect” in which a beta-2 receptor blockade may lead to the inhibition of concurrent vasodilatation, which would normally mitigate the actions of cocaine. Furthermore, systemic inhibition of vasodilatation by a beta-2 receptor blockade leading to an “unopposed alpha effect” may also cause a significantly elevated systemic blood pressure.
