The adrenergic antagonists

The adrenergic antagonists are classified according to their relative affinities for ? or ? receptors in the sympathetic nervous system.
1-?-adrenergic blocking agents
Drugs that block ? adrenoceptors profoundly affect blood pressure. Because normal sympathetic control of the vasculature occurs in large part through agonist actions on ?-adrenergic receptors, blockade of these receptors reduces the sympathetic tone of the blood vessels, resulting in decreased peripheral vascular resistance.
A. Phenoxybenzamine
Phenoxybenzamine is nonselective, linking covalently to both ?1 and ?2 receptors. The block is irreversible and noncompetitive, and the only way the body can overcome the block is to synthesize new adrenoceptors, which requires a day or longer. Therefore, the actions of phenoxybenzamine last about 24 hours. After the drug is injected, a delay of a few hours occurs before a blockade develops.
Pharmacological action
a. Cardiovascular effects: By blocking ? receptors, phenoxybenzamine prevents vasoconstriction of peripheral blood vessels by endogenous catecholamines. The decreased peripheral resistance provokes a reflex tachycardia. Furthermore, the ability to block presynaptic inhibitory ?2 receptors in the heart can contribute to an increased cardiac output. [Note: Blocking these receptors results in more norepinephrine release, which stimulates ?1 receptors on the heart, increasing cardiac output.] Thus, the drug has been unsuccessful in maintaining lowered blood pressure in hypertension, and it is no longer used for this purpose.
b. Epinephrine reversal: All ?-adrenergic blockers reverse the ? agonist actions of epinephrine