Joseph De Soto MD, PhD, FAIC

Overview The adrenergic antagonist bind adrenoreceptors either reversibly or irreversibly preventing or reducing activation by endogenous catecholamine's. Many of these drugs are used to treat disorders of the cardiovascular system. The α-receptor blockers tend to cause a decrease in peripheral vascular resistance many time resulting in reflex tachycardia and postural hypotension. These drugs may be used to treat pheochromocytoma and prostate hyperplasia. The β-receptor blockers lower blood pressure but do not cause postural hypotension and are frequently used to treat hypertension, angina, cardia arrhythmias, myocardial infarctions, heart failure, glaucoma, hyperthyroidism and prevention of migraine headache.

Irreversible Alpha 1 & Alpha 2 Blockers Phenoxybenzamine Phenoxybenzamine: this medication is a nonselective α blocker and binds irreversibly and noncompetitively. New receptors must be synthesized and recovery may take over a day until this happens. This medication is used pre-surgically to treat pheochromocytoma, and is useful for frostbite and Raynaud’s syndrome. This medication can be used to reverse the effects of epinephrine and more than reverse the effects of norepinephrine. The blockage of the alpha receptors causes vasodilation and reflex tachycardia to occur. This limits it ability to be used as a hypertensive medication. Side effects are reduced Ejaculation, postural hypertension, reflex tachycardia, sinus congestion and vomiting.

Reversible Alpha 1 & Alpha 2 Blockers Phentolamine Phentolamine: is a reversible inhibitor of the α- receptors and causes a block of these receptors for about 4 hours. This drug can also reverse epinephrine and more than reverse norepinephrine. This drug is can cause reflex tachycardia and postural hypertension and cause arrhythmias and angina. Hence, it should not be used if the patient has coronary artery disease. Phentolamine is used for the short term management of pheochromocytoma,to prevent necrosis due to epinephrine extravasation, and to prevent hypertensive crisis in the case of abrupt clonidine removal or tyramine induced for those on MAOI’s.

Alpha 1 Blockers Prazosin, Doxazosin & Terazosin Prazosin, Doxazosin & Terazosin: are competitive blockers of the α1 blockers and may be useful in treating hypertension and benign prostatic hyperplasia. These medications relax the α1A receptors of the prostate and bladder and the α1B receptors of the blood vessels. These drugs unlike nonselective alpha blockers cause minimal changes in cardiac output, renal blood flow, and glomerular filtration rate. By NOT blocking the α2 receptor reflex tachycardia is prevented. These drugs have a first dose response where their may be exaggerated drop of blood pressure hence, the initial dose should be about half the normal dose initiated afterwards. Side effects are lack of energy, mild orthostatic hypertension, impaired ejaculation and nasal congestion.

Alpha 2 Blockers Yohimbine Yohimbine: is a competitive antagonist for the α2-adrenergic receptor, moderate affinity for the α1 receptor. It was once considered a pure α2- adrenergic receptor blocker. At high levels it also block serotonin and dopamine receptors. Thus drug can be used for erectile dysfunction. Low doses of yohimbine can increase blood pressure by blocking α2 receptor while large amounts can dangerously lower blood pressure by binding the α1 receptor. Side effects include: priapism, hallucination, headaches, cold sweats, insomnia, panic attacks and tachycardia.

Beta Blockers Beta blockers reduce hypertension but tend not to induce postural hypotension. The beta blocker may initially cause a slight increase in blood pressure as the may block the β2 receptor initially prior to the blockage of the β1 receptor. Glucagon, is used in the treatment of overdose of beta-blockers,it increases the strength of heart contractions, increases intracellular cAMP, and decreases renal vascular resistance. Bronchospasm is treated with Ipratropium.

Poor lipid profile Weight gain

Non-Selective Beta Blockers Propranolol Propanolol: is a nonselective beta blocker. It is used to treat high blood pressure, a number of heart arrhythmias, thyrotoxicosis, glaucoma. essential tremors, esophageal varices and to prevent migraine headaches. It is also used in those who have had previous myocardial infarctions and angina. Propanolol does not slowdown normal heart beat. It is a memory damper and can be used to plant false memories. Adverse affect include insomnia, sodium retention, nightmares, lower the threshold for hyperglycemia. Half-Life: The main metabolite 4-hydroxypropranolol is active and has half-life about 6 hours while propanolol has a half life of 3-4 hours.

Non-Selective Beta Blockers Propranolol Propanolol should NOT be used if there is asthma, cocaine toxicity, bradycardia, shock, pregnancy, myasthenia gravis. Propanolol can mask thyrotoxicosis and hyperglycemia. More recently propanolol has been used experimentally to treat infantile hemangiomas. A hemangioma is a growth of the endothelial cells that line blood vessels, and is characterized by increased number of normal or abnormal vessels filled with blood

Non-Selective Beta Blockers Nadolol and Timolol Nadolol: is a non-selective beta blocker with a slight preference for β1 over β2 used in the treatment of high blood pressure and angina. It is used in the treatment of atrial fibrillation, migraine headaches, and complications of cirrhosis. Side effects include dizziness, impotence, bronchoconstriction, depression, water loss and fatigue. Timolol: is a non-selective beta blocker the oral form of timolol is used to treat high blood pressure, angina, myocardial ischemia while the topical form is used to treat open angle glaucoma. Side effects cardiac arrhythmias, severe bronchospasms, fainting, congestive heart failure, depression, confusion, worsening of Raynaud's syndrome and impotence.

Glaucoma Timolol, levobunolol, carteleolol and betaxalol (this is a selective β1 antagonist)are used in the treatment of open – angle glaucoma. These drugs slow down the production of aqueous humor by the eye and hence can be used to treat open-angle glaucoma Carbonic anhydrase inhibitors also decrease the production of aqueous humor. Prostaglandin analogues and Cholinergic agonists help with the outflow of aqueous outflow, Pilocarpine is the drug of choice for closed angle glaucoma.

Selective Beta 1 Antagonists Atenolol, Esmolol, Metoprolol, Betaxolol Atenolol, Esmolol, Metoprolol, Betaxolol; these drugs are selective β1 antagonists. These drugs do not have the unwanted side-effects of bronchoconstriction. At very high doses these drugs will start to antagonize the β2 receptor. These drugs lower blood pressure in hypertension and increase exercise tolerance in angina. Hence, these drugs are useful in those with pulmonary issues and hypertension. Beta Blockers are fourth line in the treatment of hypertension in part due to negative lipid profiles and provoking diabetes.

Selective Beta 1 Antagonists Atenolol & Metoprolol Atenolol: is a selective β1 receptor antagonist, atenolol was developed as a replacement for propranolol in the treatment of hypertension in Unlike propranolol, atenolol does not pass through the blood– brain barrier and cannot be used to prevent Migraines. hours. This drug also treats angina, and is used post myocardial infarction. Half Life 6-7. Metoprolol: is a selective β1 receptor antagonist and unlike atenolol can pass through the blood brain barrier. This drug is often combine with the diuretic hydrochlorothiazide to treat high blood pressure. This medication may be used to treat high blood pressure, angina, and to prevent further heart problems after myocardial infarction. Half Life 3- 7 hours.

Partial Agonist/Antagonist Beta receptors Acebutolol & Pindolol Acebutolol is a partial agonist at the β1 receptor while Pindolol is a partial agonist at the β1 and β2 receptors. These drugs act as antagonist in the presence of norepinephrine and epinephrine. This partial agonist activity improves the poor lipid profile normally seen in pure antagonists. These medications are useful in hypertensive patients with bradycardia. These medications are not used in angina or arrhythmias due to their partial agonist activity. Pindolol can be used in premature ejaculation. A rare lupus erythematosus-like syndrome has been associated with Acebutolol.

Alpha & Beta Antagonist Labetolol & Carvedilol Labetalol and carvedilol: are nonselective α1 and β blockers that produce peripheral vasodilation. Labetalol is also used as an alternative to methyldopa in the treatment of pregnancy associated hypertension. Carvedilol has been shown to be useful also in congestive heart failure and it thickens the cardiac wall after MI. Side effects include orthostatic hypotension and dizziness.

Adrenergic Neurotransmitter Release Inhibitors Reserpine Reserpine: is an antipsychotic and antihypertensive drug that has been used for the control of high blood pressure and for the relief of psychotic symptoms. Reserpine irreversibly blocks the vesicular monoamine transporter (VMAT). This transporter normally transports free intracellular norepinephrine, serotonin, and dopamine in the presynaptic nerve terminal into presynaptic vesicles for subsequent release into the synaptic cleft. Side effects include nasal congestion, nausea, vomiting, weight gain, gastric ulceration, stomach cramps, diarrhea, erectile dysfunction, hypotension, and depression. Parkinsonism occurs in a dose dependent manner.