therapy to reduce blood pressure, but only if the use of ace inhibitors, angiotensin-ii receptor blockers, calcium channel blockers, or thazide diuretics (in full dose or in combinations) have not been efficacious. drug interactions as with any drug, there are drug interactions that can occur with alpha blockers. for instance, alpha blockers that are used for the reduction of blood pressure, such as phenoxybenzamine or phentolamine can have synergy with other drugs that affect smooth muscle, blood vessels, or drugs used for erectile dysfunction (i.e. sildenafil, tamsulosin, etc.). this stimulates exaggerated hypotension. alternative alpha blockers, such as prazosin, tamsulosin, doxazosin, or terazosin can have adverse interactions with beta blockers, erectile dysfunction drugs, anxiolytics, and antihistamines. again, these interactions can cause dangerous hypotension. furthermore, in rare cases, drug interactions can cause irregular, rapid heartbeats or an increase blood pressure. yohimbine can interact with stimulants, hypertension drugs, naloxone, and clonidine. interactions with such drugs can cause either an unintended increase in blood pressure or potentiate an increase in blood pressure. finally, in drugs with both alpha and beta blocking properties, such as carvedilol and labetalol, interactions with other alpha or beta blockers can exaggerate a decrease in blood pressure. conversely, there are also drug interactions with carvedilol or labetalol in which blood pressure is increased unintentionally (such as with cough and cold medications). finally, there may also be some alpha/beta blocker drug interactions that can worsen previous heart failure. mechanism of action alpha blockers work by blocking the effect of nerves in the sympathetic nervous system. this is done by binding to the alpha receptors in smooth muscle or blood vessels. α-blockers can bind both reversibly and irreversibly. there are several α receptors throughout the body where these drugs can bind. specifically, α1 receptors can be found in most vascular smooth muscle, the pupillary dilator muscle, the heart, the prostate, and pilomotor smooth muscle. on the other hand, α2 receptors can be found in platelets, cholinergic nerve terminals, some vascular smooth muscle, postsynaptic cns neurons, and fat cells. the structure of α receptors is a classic g protein–coupled receptors (gpcrs) consisting of 7 transmembrane domains, which form three intracellular loops and three extracellular loops. these receptors couple to heterotrimeric g proteins composed of α, β, and γ subunits. although both of the α receptors are gpcrs, there are large differences in their mechanism of action. specifically, α1 receptors are characterized as gq gpcrs, signaling through phospholipase c to increase ip3 and dag, thus increasing the release of calcium. meanwhile, α2 receptors are labeled as gi gpcrs, which signal through adenylyl cyclase to decrease camp. because the α1 and α2 receptors have different mechanisms of action, their antagonists also have different effects. α1 blockers can inhibit the release of ip3 and dag to decrease calcium release, thus, decreasing overall signaling. on the other hand, α2 blockers prevent the reduction of camp, thus leading to an increase in overall signaling. alpha-1 receptor signaling cascade and antagonist signaling cascade. alpha-2 receptor signaling cascade and antagonist signaling cascade.