An adrenergic antagonist is a drug that inhibits the function of adrenergic receptors. There are five adrenergic receptors, which are divided into two groups. The first group of receptors are the beta (β) adrenergic receptors. There are β₁, β₂, and β₃ receptors. The second group contains the alpha (α) adrenoreceptors. There are only α₁ and α₂ receptors. Adrenergic receptors are located near the

heart The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...

s, lungs, and gastrointestinal tract. There are also α-adreno receptors that are located on

vascular smooth muscle Vascular smooth muscle is the type of smooth muscle that makes up most of the walls of blood vessels. Structure Vascular smooth muscle refers to the particular type of smooth muscle found within, and composing the majority of the wall of blood ve ...

. Antagonists reduce or block the signals of

agonists An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agon ...

. They can be drugs, which are added to the body for therapeutic reasons, or endogenous ligands. The α-adrenergic antagonists have different effects from the β-adrenergic antagonists.

Pharmacology

Adrenergic ligands are endogenous proteins that modulate and evoke specific

cardiovascular The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...

effects. Adrenergic antagonists reverse the natural cardiovascular effect, based on the type of adrenoreceptor being blocked. For example, if the natural activation of the α₁-adrenergic receptor leads to

vasoconstriction Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vess ...

, an α₁-adrenergic antagonist will result in

vasodilation Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstrictio ...

. Some adrenergic antagonists, mostly β antagonists, passively diffuse from the gastrointestinal tract. From there, they bind to

albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins ...

and α1-acid glycoprotein in the plasma, allowing for a wide spread through the body. From there, the

lipophilic Lipophilicity (from Greek λίπος "fat" and φίλος "friendly"), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves lipo ...

antagonists are metabolized in the liver and eliminated with urine while the

hydrophilic A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are ...

ones are eliminated unchanged.Stereospecific Pharmacokinetics and Pharmacodynamics of Beta-Adrenergic Blockers in Humans
Mehvar, R., & Brocks, D. R. (2001). Stereospecific pharmacokinetics and pharmacodynamics of beta-adrenergic blockers in humans.

Mechanisms of action

There are three different types of antagonists.

Competitive

While only a few α-adrenergic antagonists are competitive, all β-adrenergic antagonists are competitive antagonists. Competitive antagonists are a type of reversible antagonists. A competitive antagonist will attach itself to the same

binding site In biochemistry and molecular biology, a binding site is a region on a macromolecule such as a protein that binds to another molecule with specificity. The binding partner of the macromolecule is often referred to as a ligand. Ligands may includ ...

of the receptor that the agonist will bind to. Even though it is in activator region, the antagonist will not activate the receptor. This type of binding is reversible as increasing the concentration of agonist will outcompete the concentration of antagonist, resulting in receptor activation. Adrenergic competitive antagonists are shorter lasting than the other two types of antagonists. While the antagonists for alpha and beta receptors are usually different compounds, there has been recent drug development that effects both types of the adrenoreceptors. Phentolamine Structural Formulae

Examples

Two examples of competitive adrenergic antagonists are

propranolol Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance an ...

and

phentolamine Phentolamine, sold under the brand name Regitine among others, is a reversible nonselective α- adrenergic antagonist. Mechanism Its primary action is vasodilation due to α1 blockade. Non-selective α-blockers can cause a much more pronounced ...

. Phentolamine is a competitive and nonselective α-adrenoreceptor antagonist. Propranolol is a β-adrenoreceptor antagonist.

Non-competitive

While competitive antagonists bind to the agonist or ligand binding site of the receptor reversibly, non-competitive antagonists can either bind to the ligand site or other site called the

allosteric site In biochemistry, allosteric regulation (or allosteric control) is the regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site. The site to which the effector binds is termed the ''allosteric site ...

. A receptor's agonist does not bind to its allosteric binding site. The binding of a non-competitive antagonist is irreversible. If the non-competitive antagonist binds to the allosteric site and an agonist binds to the ligand site, the receptor will remain unactivated. An example of an adrenergic non competitive antagonists is phenoxybenzamine. This drug is a non-selective α-adrenergic antagonist, which means it binds to both alpha receptors.

Uncompetitive

There were few if any adrenergic uncompetitive antagonists. An uncompetitive antagonist is slightly different from the other two types of antagonists. The action of an uncompetitive antagonist is dependent on the receptor's prior activation. This means only after the agonist binds to the receptor can the antagonist block the receptor's function.

Examples

Alpha blockers

Phentolamine Phentolamine, sold under the brand name Regitine among others, is a reversible nonselective α- adrenergic antagonist. Mechanism Its primary action is vasodilation due to α1 blockade. Non-selective α-blockers can cause a much more pronounced ...

phenoxybenzamine Phenoxybenzamine (marketed under the trade names Dibenzyline and Dibenyline) is a non-selective, irreversible alpha blocker. Uses It is used in the treatment of hypertension, and specifically that caused by pheochromocytoma. It has a slower ons ...

Tamsulosin Tamsulosin, sold under the brand name Flomax among others, is a medication used to treat symptomatic benign prostatic hyperplasia (BPH) and chronic prostatitis and to help with the passage of kidney stones. The evidence for benefit with a ki ...

Beta blockers

Propranolol Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance an ...

* Nebivilol *

Atenolol Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. Atenolol, however, does not seem to improve mortality in those with high blood pressure. Other uses include the prevention of mi ...

* Oxprenolol *

Metoprolol Metoprolol, sold under the brand name Lopressor, among others, is a selective β1 receptor blocker medication. It is used to treat high blood pressure, chest pain due to poor blood flow to the heart, and a number of conditions involving an a ...

* Timolol * Pindolol *

Nadolol Nadolol, sold under the brand name Corgard among others, is a medication used to treat high blood pressure, heart pain, atrial fibrillation, and some inherited arrhythmic syndromes. It has also been used to prevent migraine headaches and compl ...

* Pindolol * Esmolol * Acebutolol * Sotalol * Talinolol * Betaxolol

Mixed action

Labetalol Labetalol is a medication used to treat high blood pressure and in long term management of angina. This includes essential hypertension, hypertensive emergencies, and hypertension of pregnancy. In essential hypertension it is generally less pref ...

* Carvedilol

Major effects

Main complications of persistent high blood pressure

Adrenergic antagonists have inhibitory or opposing effects on the receptors in the adrenergic system. The adrenergic system modulates the

fight-or-flight response The fight-or-flight or the fight-flight-or-freeze response (also called hyperarousal or the acute stress response) is a physiological reaction that occurs in response to a perceived harmful event, attack, or threat to survival. It was first des ...

. Since this response, which is mostly seen as an increase in blood pressure, is produced by the release of the endogenous adrenergic ligands, administration of an adrenergic antagonist results a decrease in blood pressure, which is controlled by both heart rate and vasculature tone. Administration of an adrenergic antagonist that specifically targets the beta receptors, results in this decrease in blood pressure by slowing or reducing cardiac output.

Medical uses

Adrenergic antagonists are mostly used for cardiovascular disease. The adrenergic antagonists are widely used for lowering blood pressure and relieving hypertension. These antagonists have a been proven to relieve the pain caused by

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...

, and also the infarction size, which correlates with heart rate. There are few non-cardiovascular uses for adrenergic antagonists. Alpha-adrenergic antagonists are also used for treatment of ureteric stones, pain and

panic disorder Panic disorder is a mental and behavioral disorder, specifically an anxiety disorder characterized by reoccurring unexpected panic attacks. Panic attacks are sudden periods of intense fear that may include palpitations, sweating, shaking, short ...

s, withdrawal, and anesthesia.

Limitations

While these adrenergic antagonists are used for treating cardiovascular disease, mainly hypertension, they can evoke harmful cardiac events through prolongation of the QT interval. Some adrenergic antagonists have a diminished ability to reduce stroke compared to

placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. In general, placebos can af ...

drugs.

Side effects and toxicity

While adrenergic antagonists have been used for years, there are multiple issues with using this class of drug. When overused, adrenergic antagonists can result in bradycardia,

hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...

, hyperglycemia and even hypodynamic shock. This is because adrenergic stimulation by agonists results in normal calcium channel regulation. If these adrenergic receptors are blocked too often, there will be an excess in calcium channel inhibition, which causes most of these problems.

References

External links

* {{DEFAULTSORT:Adrenergic Antagonist Antihypertensive agents Parasympathomimetics

Pharmacology

Mechanisms of action

Competitive

Examples

Non-competitive

Uncompetitive

Examples

Alpha blockers

Beta blockers

Mixed action

Major effects

Medical uses

Limitations

Side effects and toxicity

See also

References

External links