Adrenergic blocking agents are a class of drugs that exhibit its pharmacological action through inhibiting the action of the

sympathetic nervous system The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of th ...

in the body. The sympathetic nervous system(SNS) is an

autonomic nervous system The autonomic nervous system (ANS), formerly referred to as the vegetative nervous system, is a division of the peripheral nervous system that supplies viscera, internal organs, smooth muscle and glands. The autonomic nervous system is a control ...

that we cannot control by will. It triggers a series of responses after the body releases chemicals named noradrenaline and

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...

. These chemicals will act on

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 beta ...

s, with subtypes

Alpha-1 Alpha 1 or Alpha-1 may refer to: * Alpha-1 adrenergic receptor, a G protein-coupled receptor * Alpha-1 antitrypsin, a protein **Alpha-1 antitrypsin deficiency, a genetic disorder *Alpha-1-fetoprotein or Alpha-fetoprotein, a protein *Alpha-One, a fi ...

, Alpha-2, Beta-1, Beta-2, Beta-3, which ultimately allow the body to trigger a "fight-or-flight" response to handle external stress. These responses include vessel constriction in general vessels whereas there is vasodilation in vessels that supply

skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

s or in

coronary vessels Coronary () may, as shorthand in English, be used to mean: * Coronary circulation, the system of arteries and veins in mammals ** Coronary artery disease ** Coronary occlusion ** A myocardial infarction, a heart attack As adjective * Referring t ...

. Additionally, the heart rate and contractile force increase when SNS is activated, which may be harmful to

cardiac function Cardiac physiology or heart function is the study of healthy, unimpaired function of the heart: involving blood flow; myocardium structure; the electrical conduction system of the heart; the cardiac cycle and cardiac output and how these interact a ...

as it increases metabolic demand. Adrenergic blocking agents treat certain diseases through blocking the

, preventing it from being activated by noradrenaline and

. As a result, it stops the body from producing the "fight-or-flight" responses.

Medical Uses

There are drugs that are approved by the Food and Drug Administration (FDA), whereas there are some off-label uses as well.

Alpha 1 blocker

The alpha blockers mostly act in our

smooth muscle Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...

s, especially the ones that control the size of vessels. Thus, alpha1 blockers can dilate blood vessels and decrease the

blood pressure Blood pressure (BP) is the pressure of 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 "blood pressure" r ...

. Depending on its site of action, it can be used to treat different diseases. They can be used to treat signs and symptoms of benign prostatic hyperplasia,

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

(but not as first line agent), pheochromocytoma, extravasation management and reversal of local

anesthesia Anesthesia 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 prevention of pain), paralysis (muscle relaxation), ...

There are some off- label use as well, such as chronic prostatitis and lower urinary tract symptoms in males, ureteral calculus expulsion, ureteral stent-related urinary symptoms. It can be used in post-traumatic stress disorder,

Raynaud phenomenon Raynaud syndrome, also known as Raynaud's phenomenon, eponymously named after the physician Auguste Gabriel Maurice Raynaud, who first described it in his doctoral thesis in 1862, is a medical condition in which the spasm of small arteries cau ...

, hypertensive crisis, Extravasation of sympathomimetic vasopressors, problem with urine related to neurogenic bladder, functional outlet obstruction and partial prostate obstruction.

Alpha 2 blocker

Alpha2 blocker reduces the transmission of

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

s circulating around the body, which contributes to contraction of

. Instead of treating diseases, they are used as antidotes for reversing overdose of alpha-2 agonist, reducing the toxic effect of the agonist. Only limited indications are present for this drug. More research is in progress to investigate the possible use of alpha2 blockers.

Beta 1 blocker

Since beta 1 receptor are mainly located in the heart, most beta 1 blockers take abnormalities associated with the heart as the target. It treats medical conditions like

arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

chest pain Chest pain is pain or discomfort in the chest, typically the front of the chest. It may be described as sharp, dull, pressure, heaviness or squeezing. Associated symptoms may include pain in the shoulder, arm, upper abdomen, or jaw, along with n ...

, myocardial infarction. It treats other symptoms unrelated to heart like

migraine Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...

s and anxiety.

Beta 2 blocker

Beta2 blockers promote vasodilation in some tissues as mentioned above( arterioles in

s or ciliary muscle in the

eye Eyes are organs of the visual system. They provide living organisms with vision, the ability to receive and process visual detail, as well as enabling several photo response functions that are independent of vision. Eyes detect light and conv ...

etc.). Currently, there is no beta-2 blocker with

FDA approval The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...

Butoxamine Butaxamine (INN, also known as butoxamine) is a β2-selective beta blocker. Its primary use is in experimental situations in which blockade of β2 receptors is necessary to determine the activity of the drug (i.e. if the β2 receptor is compl ...

, an example of beta 2 blocker, has no clinical use but is used in research.

Beta 3 blocker

Due to the relatively limited study on beta-3 receptor, there is not much development of beta-3 blocker. Therefore, beta-3 blocker has no clinical use now.

Adverse Effect

Selectivity

Some drugs, being non-selective, can exert actions on 2 or more different receptors. Examples include non-selective beta blocker, which block both beta-1 receptor and

beta-2 receptor The beta-2 adrenergic receptor (β2 adrenoreceptor), also known as ADRB2, is a cell membrane-spanning beta-adrenergic receptor that binds epinephrine (adrenaline), a hormone and neurotransmitter whose signaling, via adenylate cyclase stimulati ...

as well.

Non-selective alpha blocker

The adverse effects of non-selective alpha blockers are caused by the autonomic response to the systemic changes induced by the adrenergic blocking agents. The common adverse effects of alpha blockers are due to the blockade of alpha-1

s in tissue that requires high level of alpha adrenergic sympathetic input such as arterial resistance, vascular capacitance and the outflow tract of the urinary bladder. The undesirable symptoms are mentioned in the following 'selective alpha-1 blocker' part.

Selective alpha 1 blocker

With the vasodilation and

relaxation caused by alpha-1 blockers, around 10 to 20% of patients present undesirable effects of asthenia(weakness), dizziness,

faintness Syncope, commonly known as fainting, or passing out, is Unconsciousness, a loss of consciousness and muscle strength characterized by a fast onset, short duration, and spontaneous recovery. It is caused by a decrease in blood flow to the brain ...

and syncope. Other adverse outcomes that are even more uncommon include

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

, drowsiness,

palpitations Palpitations are perceived abnormalities of the heartbeat characterized by awareness of cardiac muscle contractions in the chest, which is further characterized by the hard, fast and/or irregular beatings of the heart. Symptoms include a rapi ...

, urinary incontinence and

priapism Priapism is a condition in which a penis remains erect for hours in the absence of stimulation or after stimulation has ended. There are three types: ischemic (low-flow), nonischemic (high-flow), and recurrent ischemic (intermittent). Most cases ...

. Mild body weight gain of 1–2 kg, which may be associated with

secondary hyperaldosteronism Hyperaldosteronism is a medical condition wherein too much aldosterone is produced by the adrenal glands, which can lead to lowered levels of potassium in the blood ( hypokalemia) and increased hydrogen ion excretion (alkalosis). This cause of m ...

, is also observed in some patients. Orthostatic Hypertension demonstration

The alpha-1 blockers are associated with the first-dose effect, which refers to the tachycardia response and orthostatic hypotension that caused by the systemic vasodilation at the initial administration of alpha-1 blockers. After the first administration, patients may experience a short period of orthostatic hypotension with a sensation of intense

, which is aggravated by upright posture, intravascular volume depletion or concurrent administration of other

antihypertensive Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Evidence suggests tha ...

medications.

Selective alpha 2 blocker

Apart from increasing the noradrenaline release, the selective alpha-2 blockers have the potential to bind with other receptors such as the 5-HT

serotonin receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neur ...

. However, the serotonin receptor antagonism has side effects such as weight gain and impaired movement. Hence, alpha-2 blockers are not used clinically due to its extensive binding. Similar to the alpha-1 blocker, the alpha-2 family will also present the first-dose effect, but it is generally less pronounced compared with the alpha-1 blockers.

Non-selective beta blocker

The Central Nervous System (CNS) side effects of beta blockers including sleep impairment, dreaming,

nightmare A nightmare, also known as a bad dream, Retrieved 11 July 2016. is an unpleasant dream that can cause a strong emotional response from the mind, typically fear but also despair, anxiety or great sadness. The dream may contain situations of d ...

s and hallucinations are generally small. Also, the effects on

short-term memory Short-term memory (or "primary" or "active memory") is the capacity for holding a small amount of information in an active, readily available state for a short interval. For example, short-term memory holds a phone number that has just been recit ...

are minimal.

Selective beta 1 blocker

Depiction of a person suffering from heart failure

The cardio-selective beta-1 blockers could cause adverse effects including

bradycardia Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, a ...

, reduced exercise ability, hypotension, atrioventricular nodal blockage and

. Other possible adverse effects include nausea and vomiting, abdominal discomfort, dizziness, weakness,

fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

, and dryness in mouth and eye. Sexual impairment, memory loss, and confusion are regarded as rare side effects. For diabetic patients, there is an extra risk of masking hypoglycemia-induced tachycardia, while a continuous hypoglycemia could cause acute brain damage.

Selective beta 2 blocker

The blockade of beta-2 receptors will result in vasoconstriction and

constriction, and the effects are similar to the

agonism Agonism (from Greek ἀγών '' agon'', "struggle") is a political and social theory that emphasizes the potentially positive aspects of certain forms of conflict. It accepts a permanent place for such conflict in the political sphere, but seeks ...

of alpha-1 receptors. The side effects include

, tachycardia,

and subcutaneous ischemia at the site of injection. Other possible side effects include

, hypoglycemia during exercise, muscle cramps, and increase of airway resistance.

Selective beta 3 blocker

Due to the relatively limited study on beta-3 receptor, there is not much development of beta-3 blocker. Therefore, there is limited information on the adverse effects caused by beta-3 blocker.

Contraindications

Alpha 1 blocker

As alpha 1 blocker will dilate blood vessels, it lowers the

. Thus, it contraindicate to patients with a history of orthostatic hypotension and in current use of phosphodiesterase inhibitors. Moreover, alpha 1 blocker should not be given to patients with

since it expands

blood volume Blood volume (volemia) is the volume of blood (blood cells and plasma) in the circulatory system of any individual. Humans A typical adult has a blood volume of approximately 5 liters, with females and males having approximately the same blood per ...

Alpha 2 blocker

There are limited information about the contraindication of alpha-2 blocker, since it has limited clinical uses.

Beta 1 blocker

Traditionally, Beta-1 blocker has several contraindications, including, recent history of fluid retention without use of diuretics, and complete or second degree of heart block. Whilst some studies suggest that there are only minor differences in terms of adverse effect between asthma patients and non-asthma patients, beta-1 blockers are generally not prescribed to asthma patients or patients with chronic obstructive pulmonary disease, due to its potential blockage of beta 2 receptors. Additionally, beta1 blocker should not be given to patients with

peripheral vascular diseases Peripheral artery disease (PAD) is an abnormal narrowing of arteries other than those that supply the heart or brain. When narrowing occurs in the heart, it is called coronary artery disease, and in the brain, it is called cerebrovascular dise ...

, diabetes mellitus, since blockage of beta-2 receptors may lead to vasoconstriction and delayed response to hypoglycemia respectively.

Beta 2 blocker

Beta 2 blocker should be avoided for patients with asthma, COPD as it causes bronchoconstriction. It may also increase the chance of

hypoglycemic Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose belo ...

comas in diabetic patients.

Beta 3 blocker

Due to the relatively limited study on beta-3 receptor, there is not much development of beta-3 blocker. Therefore, beta-3 blocker has no clinical use. The contraindications of beta-3 blocker can not be observed.

Overdose effects

Alpha 1 blocker

Blausen 0703 Parasympathetic Innervation

Overdose of alpha-1 blocker will lead to an unopposed parasympathetic activity. Symptoms include

, hypotension,

miosis Miosis, or myosis (), is excessive constriction of the pupil.Farlex medical dictionary
citing: ...

and

sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...

Alpha 2 blocker

There is a lack of information regarding toxicity caused by overdose of alpha-2 blocker, due to its limited clinical uses.

Beta 1 blocker

Toxicity of beta-1 blocker will contribute to symptoms including

, hypotension, due to its extensive blockage of beta-1 receptor. Moreover, overdose of beta-1 blocker may lead to the lost of their selectivity and bind to

, causing bronchopulmonary symptoms. Overdose of lipophilic beta-1 blocker can disturb neurologic functioning, which eventually lead to altered mental states. To mitigate the toxicity of Beta-1 blocker,

glucagon Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medicati ...

, salts like calcium and

sodium bicarbonate Sodium bicarbonate (IUPAC name: sodium hydrogencarbonate), commonly known as baking soda or bicarbonate of soda, is a chemical compound with the formula NaHCO3. It is a salt composed of a sodium cation ( Na+) and a bicarbonate anion ( HCO3−) ...

, magnesium sulfate are used to reverse beta-1-blocker effect and treating hypotension respectively.

Beta 2 blocker

Similar to alpha-2 blocker, there is a lack of information about beta-2 blocker's toxicity, due to its limited clinical uses.

Beta 3 blocker

Due to the relatively limited study on beta-3 receptor, there is not much development of beta-3 blocker. Therefore, there is not much information regarding the toxic effect of beta-3 blocker.

Drug Interaction

Alpha 1 blocker

CYP3A4 inhibitors

Alpha-1 blockers such as

Alfuzosin Alfuzosin, sold under the brand names Alfosoft and Uroxatral, among others, is a medication of the α1 blocker class. It is used to treat benign prostatic hyperplasia (BPH). As an antagonist of the α1 adrenergic receptor, it works by relax ...

Doxazosin Doxazosin, sold under the brand names Cardura among others, is a medication used to treat symptoms of benign prostatic hyperplasia (enlarged prostate) and hypertension (high blood pressure). For high blood pressure, it is a less preferred option. ...

, Tamsulosin and

Silodosin Silodosin (known by the trade names Silosoft in India, Urief in Japan, Rapaflo in North America, and Silodyx or Niksol in the European Union) is a medication for the symptomatic treatment of benign prostatic hyperplasia (BPH). It acts as an α1- ...

involve CYP450 enzyme metabolism, particularly by CYP3A4. Alpha-1 blockers will conjugate in glucuronidation during metabolism. CYP3A4 inhibitors inhibit glucuronidation and hence reduce the glucuronide-conjugated

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

. Hence, potent CYP3A4 inhibitors can potentially increase their exposure to those alpha blockers. However, there are no clinically significant evidence supporting the drug interaction between alpha-1 blocker and CYP3A4 inhibitors.

Alpha 2 blocker

Since alpha-2 blocker has limited clinical uses, there is a lack of information on drug interaction regarding alpha-2 blocker.

Beta 1 blocker

Antihypertensive drugs

Additional hypotensive effects may occur when patients are taking beta-1 blockers with other antihypertensive drugs such as

nitrates Nitrate is a polyatomic ion with the chemical formula . Salts containing this ion are called nitrates. Nitrates are common components of fertilizers and explosives. Almost all inorganic nitrates are soluble in water. An example of an insoluble ...

, PDE inhibitors,

ACE inhibitor Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of hypertension, high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease i ...

s and

calcium channel blocker Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...

s. The combination of beta blockers and antihypertensive drugs will work on different mechanism to lower

. For example, the co-administration of beta-1 blocker atenolol and ACE inhibitor lisinopril could produce a 50% larger reduction in blood pressure than using either drug alone.

Hypertensive drugs

Antihypertensive drugs and hypertensive drugs affect

in an opposite way. The most common hypertensive drugs in the UK are NSAIDs and

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...

s. NSAIDs inhibit the synthesis of

prostaglandin The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derive ...

, which increases the

and potentially reduce the efficacy of several antihypertensive drugs.

Beta 2 blocker

Since beta-2 blocker has limited clinical uses, there is a lack of information on drug interaction regarding beta-2 blocker.

Beta 3 blocker

Since beta-3 blocker is still under development, there is a lack of information on drug interaction about beta-3 blocker.

Mechanism of Action

Alpha 1 blocker

Alpha 1 blocker exerts its action on alpha-1 receptor, dilating the smooth muscles.

Alpha-1 receptor alpha-1 (α1) adrenergic receptors are G protein-coupled receptors (GPCRs) associated with the Gq heterotrimeric G protein. α1-adrenergic receptors are subdivided into three highly homologous subtypes, i.e., α1A-, α1B-, and α1D-adrenergic ...

is a Gq type G-protein coupled receptor. When it is activated, it will lead to activation of

phospholipase C Phospholipase C (PLC) is a class of membrane-associated enzymes that cleave phospholipids just before the phosphate group (see figure). It is most commonly taken to be synonymous with the human forms of this enzyme, which play an important role ...

, raising the intracellular level of IP3 and DAG. As a result, a higher intracellular concentration of Calcium is achieved, contributing to

contraction and

glycogenolysis Glycogenolysis is the breakdown of glycogen (n) to glucose-1-phosphate and glycogen (n-1). Glycogen branches are catabolized by the sequential removal of glucose monomers via phosphorolysis, by the enzyme glycogen phosphorylase. Mechanism The ...

. Alpha 1 blockers, in contrast, bind to and act as inhibitors of alpha-1 receptors, hence preventing the downstream action mentioned(increase of

, IP3 and DAG hence increase of Ca Concentration). As a result, the contraction of

is suppressed. A2 receptor signaling

Alpha 2 blocker

The alpha-2 blocker acts on alpha-2 receptors. The alpha-2 receptor is a G-protein coupled receptor as well, which exert its action by Gi function, leading to an inhibition of adenylyl cyclase and thus reducing synthesis of

cAMP Camp may refer to: Outdoor accommodation and recreation * Campsite or campground, a recreational outdoor sleeping and eating site * a temporary settlement for nomads * Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...

. It lowers the amount of calcium inside the cell. Ultimately, release of noradrenaline and

will be inhibited and

s tend to dilate. Alpha-2 blocker stops the downstream signaling pathway (inhibit adenylyl cyclase, reduce cAMP and Ca), thus lead to release of the mentioned neurotransmitters( noradrenaline and

) and contraction of

eventually.

Beta 1 blocker

Beta1 blocker will stop the action of beta-1 receptor via occupying the beta-1 receptor without any activation. The beta-1 receptor is a G-protein-coupled receptor with Gs alpha subunit as its main communication method. By signaling Gs, adenylyl cyclase is recruited to activate a

pathway, which potentiates the receptor. This kind of receptor is located at the heart, kidney and adipose tissue. Eventually, a higher

cardiac output In cardiac physiology, cardiac output (CO), also known as heart output and often denoted by the symbols Q, \dot Q, or \dot Q_ , edited by Catherine E. Williamson, Phillip Bennett is the volumetric flow rate of the heart's pumping output: t ...

(or an increased amount of

perfusion Perfusion is the passage of fluid through the circulatory system or lymphatic system to an organ or a tissue, usually referring to the delivery of blood to a capillary bed in tissue. Perfusion is measured as the rate at which blood is deliver ...

to organs) will be resulted. Moreover, more renin is released from the kidney to produce more

angiotensin II Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adre ...

, increasing the

. Moreover, it encourages lipolysis in adipose tissue. Beta-1 blocker blocks the beta-1 receptor and stops the action mentioned above. (signaling Gs, thus activate cAMP pathway by recruiting adenylyl cyclase, leading to higher

, renin release and lipolysis)

Beta 2 blocker

Beta 2 blockers cease action of

by blocking the receptor and preventing it from being activated. Similar to beta-1 receptor, the activated beta-2 receptor will lead to the detach of alpha subunit of Gs protein and attachment of adenylate cyclase. Adenosine triphosphate(ATP), is then catalyzed to form

. cAMP will facilitate release of protein kinase A as well as reduction of intracellular calcium level, relaxing the

s. Beta-2 blockers stops the above-mentioned signaling pathway, (formation of

, release of protein kinase A, reduction of intracellular calcium level) by blocking the receptor. Remarks: It has to be noted that

alpha-1 receptor alpha-1 (α1) adrenergic receptors are G protein-coupled receptors (GPCRs) associated with the Gq heterotrimeric G protein. α1-adrenergic receptors are subdivided into three highly homologous subtypes, i.e., α1A-, α1B-, and α1D-adrenergic ...

has an opposite action when it is compared with beta 2 receptor. However, the location of the two receptors differs in different tissues, which gives rise to different action of

. For example, in the

, under stimulation of

, radial muscles of the iris contract through activation of

to allow more light to enter, while the ciliary muscle in the eye relaxes through activation of

to allow far vision. In the arterioles of

, there is only mild constriction under activation of SNS, due to the balance between

alpha-1 Alpha 1 or Alpha-1 may refer to: * Alpha-1 adrenergic receptor, a G protein-coupled receptor * Alpha-1 antitrypsin, a protein **Alpha-1 antitrypsin deficiency, a genetic disorder *Alpha-1-fetoprotein or Alpha-fetoprotein, a protein *Alpha-One, a fi ...

and beta-2 receptors.

Beta 3 blocker

Beta-3 blocker will inactivate beta-3 receptor and stops the following action. Beta 3 receptor is a G-protein coupled receptor, similar to beta-1 and beta-2 receptors. The receptor is involved in G-as activation. The receptor will also stimulate adenylyl cyclase. Eventually, it will lead to effects like increase of tryptophan and

5-hydroxytryptamine Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

level, increase of lipolysis in adipose tissue. Beta-3 blocker will antagonize the receptor, which will stop the signaling pathway(G-as activation, stimulation of adenylyl cyclase).

History

Alpha Blocker

In 1978, a successful alpha blocker, phenoxybenzamine was confirmed to be clinically beneficial through a randomized, placebo-controlled study. It was the first alpha blocker which was used for treating Benign Prostatic Hyperplasia. Another Alpha Blocker

Prazosin Prazosin is an α1 blocker medication primarily used to treat high blood pressure, symptoms of an enlarged prostate, and nightmares related to post-traumatic stress disorder (PTSD). It is a less preferred treatment of high blood pressure. Other ...

, which was the first drug selective to alpha 1 receptor, was developed in 1987 for the therapy of Benign Prostatic Hyperplasia. Other alpha blockers are then introduced for several diseases.

Beta Blocker

The first beta blocker, propranolol, was introduced in the early 1960s by the winner of The Nobel Prize in Physiology or Medicine 1988-

Sir James W. Black Sir James Whyte Black (14 June 1924 – 22 March 2010) was a Scottish physician and pharmacologist. Together with Gertrude B. Elion and George H. Hitchings, he shared the Nobel Prize for Medicine in 1988 for pioneering strategies for rational ...

. The drug was originally developed in order to induce a calm effect on the heart by blocking the

beta 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 beta ...

for adrenaline, treating a range of cardiovascular disorders.

Beta 3 blocker

Unlike other subtypes of receptor, beta 3 receptors were more recently discovered in 1989. Therefore, Beta 3 blockers are still under development.

Agents

The following examples are the common adrenergic blocking agents used clinically. {, class="wikitable" , Drug , Chemical structure , Drug class , Clinical uses , Brand Name , - , Phenoxybenzamine ,

, Non-selective alpha blocker , Paroxysmal hypertension, pheochromocytoma-induced sweating , Dibenzyline , - , Phentolamine ,

, Non-selective alpha blocker , Reversal agent for unnecessary prolonged local analgesia , Regitine , - ,

, Selective alpha-1 blocker ,

Hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

, benign prostatic hyperplasia, PTSD associated

s and

, APO-PRAZO , - , Tamsulosin , Tamsulosin-2d-skeletal

, Selective alpha-1 blocker , Benign prostatic hypertrophy , HARNAL D , - , Yohimbine ,

, Selective alpha-2 blocker , Not used clinically, but available for treatment of male

erectile dysfunction Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men.Cunningham GR, Rosen RC. Overview of male ...

, PMS-YOHIMBINE , - , Propranolol , Propranolol-skeletal

, Non-selective beta blocker , Migraine prophylaxis , APO-PROPRANOLOL , - ,

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 pai ...

, Non-selective beta blocker , Glaucoma and ocular hypertension , APO-DORZO-TIMOP , - , Atenolol , Atenolol structure

, Selective beta-1 blocker ,

angina Angina, also known as angina pectoris, is chest pain or pressure, usually caused by ischemia, insufficient blood flow to the Cardiac muscle, heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typical ...

and acute myocardial infarction , ALONET , - , Metoprolol , Metoprolol structure

, Selective beta-1 blocker ,

Angina Angina, also known as angina pectoris, is chest pain or pressure, usually caused by ischemia, insufficient blood flow to the Cardiac muscle, heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typical ...

, myocardial infarction, atrial fibrillation and

, BETALOC , - , Butaxamine ,

, Selective beta-2 blocker , Not used clinically, use in animal and tissue experiments{{Cite web, last=PubChem, title=Butaxamine, url=https://pubchem.ncbi.nlm.nih.gov/compound/18026, access-date=2021-03-15, website=pubchem.ncbi.nlm.nih.gov, language=en , (not used clinical)

Non-selective alpha blocker

* Phenoxybenzamine * Phentolamine

Selective alpha 1 blocker

* Prazosin * Tamsulosin

Selective alpha 2 blocker

* Yohimbine

Non-selective beta blocker

* Propranolol * Timolol

Selective beta 1 blocker

* Atenolol * Metoprolol

Selective beta 2 blocker

* Butaxamine

Selective beta 3 blocker

* Still under development

References

Drugs Sympathetic nervous system Autonomic nervous system Adrenergic receptors