An adrenergic antagonist is a

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

that inhibits the function of

adrenergic receptor The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like b ...

s. 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 (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

lung The lungs are the primary Organ (biology), organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the Vertebral column, backbone on either side of the heart. Their ...

s, and

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

. 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 v ...

. 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 ligand In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from Latin ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a ...

s. The α-adrenergic antagonists have different effects from the β-adrenergic antagonists.

Pharmacology

Adrenergic ligands are endogenous proteins that modulate and evoke specific

cardiovascular In vertebrates, the circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of the heart a ...

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 vesse ...

, an α₁-adrenergic antagonist will result in

vasodilation Vasodilation, also known as vasorelaxation, 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. Blood vessel wa ...

. 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 of the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Alb ...

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

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

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 n ...

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 antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of recep ...

s. 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 Drug development is the process of bringing a new pharmaceutical drug to the market once a lead compound has been identified through the process of drug discovery. It includes preclinical research on microorganisms and animals, filing for regu ...

that effects both types of the adrenoreceptors. Phentolamine Structural Formulae

Examples

Two examples of competitive adrenergic antagonists are

propranolol Propranolol is a medication of the beta blocker class. It is used to treat hypertension, high blood pressure, some types of cardiac dysrhythmia, irregular heart rate, thyrotoxicosis, capillary hemangiomas, akathisia, performance anxiety, and ...

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. 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 (PBZ, 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 slowe ...

* Tamsulosin

Beta blockers

Propranolol Propranolol is a medication of the beta blocker class. It is used to treat hypertension, high blood pressure, some types of cardiac dysrhythmia, irregular heart rate, thyrotoxicosis, capillary hemangiomas, akathisia, performance anxiety, and ...

Nebivolol Nebivolol is a beta blocker used to treat high blood pressure and heart failure. As with other β-blockers, it is generally a less preferred treatment for high blood pressure. It may be used by itself or with other blood pressure medication. ...

Atenolol Atenolol is a beta blocker medication primarily used to treat high blood pressure and angina, heart-associated chest pain. Although used to treat high blood pressure, it does not seem to improve mortality rate, mortality in those with the condi ...

Oxprenolol Oxprenolol (brand names Trasacor, Trasicor, Coretal, Laracor, Slow-Pren, Captol, Corbeton, Slow-Trasicor, Tevacor, Trasitensin, Trasidex) is a non-selective beta blocker with some intrinsic sympathomimetic activity. It is used for the treatment ...

Metoprolol Metoprolol, sold under the brand name Lopressor among others, is a medication used to treat angina, high blood pressure and a number of conditions involving an abnormally fast heart rate. It is also used to prevent further heart problems afte ...

Timolol Timolol is a beta blocker medication used either by mouth or as eye drops. As eye drops it is used to treat increased pressure inside the eye such as in ocular hypertension and glaucoma. By mouth it is used for high blood pressure, chest ...

* Pindolol *

Nadolol Nadolol, sold under the brand name Corgard among others, is a medication used to treat hypertension, high blood pressure, angina pectoris, heart pain, atrial fibrillation, and some Channelopathy, inherited arrhythmic syndromes. It has also been u ...

* Pindolol *

Esmolol Esmolol, sold under the brand name Brevibloc, is a cardio selective beta-blocker, beta1 receptor blocker with rapid Onset of action, onset, a very short duration of action, and no significant intrinsic sympathomimetic or membrane stabilising acti ...

* Acebutolol *

Sotalol Sotalol, sold under the brand name Betapace among others, is a medication used to treat and prevent abnormal heart rhythms. Evidence does not support a decreased risk of death with long term use. It is taken by mouth or given by injection into ...

* Talinolol * Betaxolol

Mixed action

Labetalol Labetalol is a medication used to treat hypertension, 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 gene ...

Carvedilol Carvedilol, sold under the brand name Coreg among others, is a beta blocker medication, that may be prescribed for the treatment of high blood pressure (hypertension) and chronic heart failure with reduced ejection fraction (also known as HFrEF ...

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-freeze-or-fawn (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 describ ...

. 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 Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...

, 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 Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...

. The adrenergic antagonists are widely used for lowering blood pressure and relieving

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

. 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 Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...

, 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 Pain is a distressing feeling often caused by intense or damaging Stimulus (physiology), stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sense, sensory and emotional experience associated with, or res ...

and

panic disorder Panic disorder is a mental 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, shortness of breath ...

s, withdrawal, and

anesthesia Anesthesia (American English) or anaesthesia (British English) is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prev ...

. Adrenergic antagonists are used to treat acute cardiovascular

toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacteria, bacterium, or plant, as well as the effect o ...

(e.g. in

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended. Retrieved on September 20, 2014.

) caused by sympathomimetics, for instance caused by

amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug use, recreational or Performance-enhancing substance, performance-enhancing drug and less commonly as a secon ...

cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

ephedrine Ephedrine is a central nervous system (CNS) stimulant and sympathomimetic agent that is often used to prevent hypotension, low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred ...

, and other drugs.

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 The QT interval is a measurement made on an Electrocardiography, electrocardiogram used to assess some of the electrical properties of the heart. It is calculated as the time from the start of the QRS complex, Q wave to the end of the T wave, an ...

. Some adrenergic antagonists have a diminished ability to reduce

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

compared to

placebo A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials ...

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 Bradycardia, also called bradyarrhythmia, is a resting heart rate under 60 beats per minute (BPM). While bradycardia can result from various pathological processes, it is commonly a physiological response to cardiovascular conditioning or due ...

hypotension Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...

hyperglycemia Hyperglycemia is a condition where unusually high amount of glucose is present in blood. It is defined as blood glucose level exceeding 6.9 mmol/L (125 mg/dL) after fasting for 8 hours or 10 mmol/L (180 mg/dL) 2 hours after eating. Blood gluc ...

and even hypodynamic shock. This is because adrenergic stimulation by agonists results in normal

calcium channel A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, which are a type of calcium channel regulated by changes in membrane potential. Some calcium chan ...

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