Cholinergic
Acetylcholine
The word choline generally refers to the various quaternary ammonium salts
containing the N,N,N-trimethylethanolammonium cation. Found in most animal
tissues, choline is a primary component of acetylcholine, the neurotransmitter,
and functions with inositol as a basic constituent of lecithin. It prevents fat
deposits in the liver and facilitates the movement of fats into the cells. The richest
sources of choline are liver, kidneys, brains, wheat germ, brewer's yeast, and egg
yolk. Therefore, cholinergic often refers to the neurotransmitter acetylcholine,[1]
and is typically used in a neurological perspective. The parasympathetic nervous
system, which uses acetylcholine almost exclusively to send its messages, is said
to be almost entirely cholinergic. Neuromuscular junctions, preganglionic
neurons of the sympathetic nervous system, the basal forebrain, and brain stem
complexes are also cholinergic. In addition, the receptor for the merocrine sweat
glands are also cholinergic since acetylcholine is released from post ganglionic
sympathetic neurons.
In neuroscience and related fields, the term cholinergic is used in the following
related contexts:



A substance (or ligand) is cholinergic if it is capable of producing,
altering, or releasing acetylcholine ("indirect-acting") or mimicking its
behaviour at one or more of the body's acetylcholine receptor types
("direct-acting").
A receptor is cholinergic if it uses acetylcholine as its neurotransmitter.[2]
A synapse is cholinergic if it uses acetylcholine as its neurotransmitter.
Cholinergic drug
Structure Activity Relationship for Cholinergic Drugs
1. molecule must possess a Nitrogen atom capable of bearing a positive charge,
preferably a quarternary ammonium salt.
2. for maximum potency, the size of the alkyl groups substituted on the Nitrogen
should not exceed the size of a methyl group.
3. The molecule should have an oxygen atom, preferably an ester-like oxygen
capable of participating in a hydrogen bond.
4. There should be a two-carbon unit between the oxygen atom and the nitrogen
atom.
A cholinergic drug, also known as a cholinergic agent, cholinergic agonist,[4] or a
parasympathomimetic drug,[5] is any drug that functions to enhance the effects
mediated by acetylcholine in the central nervous system, the peripheral nervous
system, or both. These include acetylcholine's precursors and cofactors,
acetylcholine receptor agonists,acetylcholinesterase inhibitors and cholinergic
enzymes:

Acetylcholine receptor agonists
o Alvameline
o Muscarine (muscarinic receptors)
o Nicotine (nicotinic receptors)
o Pilocarpine (M3 receptors)
o Suxamethonium (muscle type receptors)
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The N,N,N-trimethylethanolammonium cation, with an undefined counteranion,
X−
Acetylcholine
The word choline generally refers to the various quaternary ammonium salts
containing the N,N,N-trimethylethanolammonium cation. Found in most animal
tissues, choline is a primary component of acetylcholine, the neurotransmitter,
and functions with inositol as a basic constituent of lecithin. It prevents fat
deposits in the liver and facilitates the movement of fats into the cells. The richest
sources of choline are liver, kidneys, brains, wheat germ, brewer's yeast, and egg
yolk. Therefore, cholinergic often refers to the neurotransmitter acetylcholine,[1]
and is typically used in a neurological perspective. The parasympathetic nervous
system, which uses acetylcholine almost exclusively to send its messages, is said
to be almost entirely cholinergic. Neuromuscular junctions, preganglionic
neurons of the sympathetic nervous system, the basal forebrain, and brain stem
complexes are also cholinergic. In addition, the receptor for the merocrine sweat
glands are also cholinergic since acetylcholine is released from post ganglionic
sympathetic neurons.
In neuroscience and related fields, the term cholinergic is used in the following
related contexts:



A substance (or ligand) is cholinergic if it is capable of producing,
altering, or releasing acetylcholine ("indirect-acting") or mimicking its
behaviour at one or more of the body's acetylcholine receptor types
("direct-acting").
A receptor is cholinergic if it uses acetylcholine as its neurotransmitter.[2]
A synapse is cholinergic if it uses acetylcholine as its neurotransmitter.
Anticholinergic
neurotransmitter
acetylcholine in the central and the peripheral nervous system. An example of an
anticholinergic is dicycloverine, and the classic example is atropine.
Anticholinergics are administered to reduce the effects mediated by acetylcholine
on acetylcholine receptors in neurons through competitive inhibition. Therefore,
their effects are reversible.
Anticholinergics are a class of medications that inhibit parasympathetic nerve
impulses by selectively blocking the binding of the neurotransmitter
acetylcholine to its receptor in nerve cells. The nerve fibers of the
parasympathetic system are responsible for the involuntary movements of
smooth muscles present in the gastrointestinal tract, urinary tract, lungs, etc.
Anticholinergics are divided into three categories in accordance with their
specific targets in the central and/or peripheral nervous system: antimuscarinic
agents, ganglionic blockers, and neuromuscular blockers.
Pharmacology
Anticholinergics are classified according to the receptors that are affected:


Antimuscarinic agents operate on the muscarinic acetylcholine receptors.
The majority of anticholinergic drugs are antimuscarinics.
Antinicotinic agents operate on the nicotinic acetylcholine receptors. The
majority of these are non-depolarising skeletal muscle relaxants for
surgical use, along with a few of the depolarising agents and drugs of
other categories structurally related to curare.
Examples of anticholinergics:




ipratropium bromide (Atrovent)
oxitropium bromide (Oxivent)
tiotropium (Spiriva)
Glycopyrrolate (Robinul)
Physostigmine is one of a few drugs that are used as antidotes for anticholinergic
poisoning. Nicotine also counteracts anticholinergics.
Effects
Anticholinergic drugs are used in treating a variety of conditions:





Gastrointestinal disorders (e.g., gastritis, pylorospasm, diverticulitis,
ulcerative colitis)
Genitourinary disorders (e.g., cystitis, urethritis, prostatitis)
Respiratory disorders (e.g., asthma, chronic bronchitis)
Parkinson's disease and Parkinson-like adverse medication effects
Sinus bradycardia - Hypersensitive vagus nerve

Insomnia, though usually only on a short term basis.
Anticholinergics generally have antisialagogue effects (decreasing saliva
production), and most have at least some sedative effect, both being
advantageous in surgical proceduresWhen a significant amount of an
anticholinergic is taken into the body, a toxic reaction known as acute
anticholinergic syndrome may result. This may happen accidentally or
intentionally as a consequence of recreational drug use. Anticholinergic drugs
are usually considered the least enjoyable by experienced recreational drug
users,[citation needed] possibly due to the lack of euphoria caused by them. In terms of
recreational use, these drugs are commonly referred to as deliriants. Because
most users do not enjoy the experience, they do not use it again, or do so very
rarely. The risk of addiction is low in the anticholinergic class. The effects are
usually more pronounced in the elderly, due to natural reduction of acetylcholine
production associated with age.
Exceptions to the above include scopolamine, orphenadrine,
dicycloverine/dicyclomine and first-generation antihistamines with central
nervous system penetration.
Possible effects of anticholinergics include:

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


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Ataxia; loss of coordination
Decreased mucus production in the nose and throat; consequent dry, sore
throat
Xerostomia or dry-mouth with possible acceleration of dental caries
Cessation of perspiration; consequent decreased epidermal thermal
dissipation leading to warm, blotchy, or red skin
Increased body temperature
Pupil dilation (mydriasis); consequent sensitivity to bright light
(photophobia)
Loss of accommodation (loss of focusing ability, blurred vision —
cycloplegia)
Double-vision (diplopia)
Increased heart rate (tachycardia)
Tendency to be easily startled
Urinary retention
Diminished bowel movement, sometimes ileus - (decreases motility via the
vagus nerve)
Increased intraocular pressure; dangerous for people with narrow-angle
glaucoma
Shaking
Possible effects in the central nervous system resemble those associated with
delirium, and may include:




Confusion
Disorientation
Agitation
Euphoria or dysphoria

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









Respiratory depression
Memory problems[2]
Inability to concentrate
Wandering thoughts; inability to sustain a train of thought
Incoherent speech
Wakeful myoclonic jerking
Unusual sensitivity to sudden sounds
Illogical thinking
Photophobia
Visual disturbances
o Periodic flashes of light
o Periodic changes in visual field
o Visual snow
o Restricted or "tunnel vision"
Visual, auditory, or other sensory hallucinations
o Warping or waving of surfaces and edges
o Textured surfaces
o "Dancing" lines; "spiders", insects; form constants
o Lifelike objects indistinguishable from reality
o Hallucinated presence of people not actually there
Rarely: seizures, coma, and death
Adrenergic agonist
An adrenergic agent is a drug, or other substance, which has effects similar to, or
the same as, epinephrine (adrenaline). Thus, it is a kind of sympathomimetic
agent. Alternatively, it may refer to something which is susceptible to
epinephrine, or similar substances, such as a biological receptor (specifically, the
adrenergic receptors).
Beta blockers block the action of epinephrine and norepinephrine in the body.
Adrenergic drugs either stimulate a response (agonists) or inhibit a response
(antagonists). The five categories of adrenergic receptors are: α1, α2, β1, β2, and
β3, and agonists vary in specificity between these receptors, and may be classified
respectively. However, there are also other mechanisms of adrenergic agonism.
Epinephrine and norepinephrine are endogenous and broad-spectrum. More
selective agonists are more useful in pharmacology.
Alpha-adrenergic agonist
An adrenergic alpha-agonist (or alpha-adrenergic agonist) is a drug that
selectively stimulates alpha adrenergic receptors. The alpha-adrenergic receptor
has two subclasses α1 and α2.
Classes
Although complete selectivity between receptor agonism is rarely achieved, some
agents have partial selectivity.
α1 agonists
Main article: Alpha-1 adrenergic receptor#agonists
α1 agonists: stimulates phospholipase C activity. (vasoconstriction and mydriasis;
used as vasopressors, nasal decongestants and eye exams). Selected examples
are:





Methoxamine
Methylnorepinephrine
Midodrine
Oxymetazoline
Phenylephrine [1]
α2 agonists
Main article: Alpha-2 adrenergic receptor#Agonists
α2 agonists: inhibits adenylyl cyclase activity. (reduce brainstem vasomotor
center-mediated CNS activation; used as antihypertensives, sedatives &
treatment of opiate and alcohol withdrawal symptoms). Selected examples are:









Clonidine (mixed alpha2-adrenergic and imidazoline-I1 receptor agonist)
Guanfacine,[2] (preference for alpha2A-subtype of adrenoceptor)
Guanabenz (most selective agonist for alpha2-adrenergic as opposed to
imidazoline-I1)
Guanoxabenz (metabolite of guanabenz)
Guanethidine (peripheral alpha2-receptor agonist)
Xylazine,[3]
Tizanidine
Methyldopa
Fadolmidine
Beta-adrenergic agonist
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Beta-adrenergic agonists are adrenergic agonists which act upon the beta
receptors
β1 agonists
Main article: Beta-1 adrenergic receptor#agonists
β1 agonists: stimulates adenylyl cyclase activity; opening of calcium channel.
(cardiac stimulants; used to treat cardiogenic shock, acute heart failure,
bradyarrhythmias). Selected examples are:




Dobutamine
Isoproterenol (β1 and β2)
Xamoterol
epinephrine
β2 agonists
β2 agonists: stimulates adenylyl cyclase activity; closing of calcium channel
(smooth muscle relaxants; used to treat asthma and COPD). Selected examples
are:

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



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

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salbutamol)
Fenoterol
Formoterol
Isoproterenol (β1 and β2)
Metaproterenol
Salmeterol
Terbutaline
Clenbuterol
Isoetarine
pirbuterol
procaterol
ritodrine
epinephrin
Beta-adrenergic agonist
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Beta-adrenergic agonists are adrenergic agonists which act upon the beta
receptors
β1 agonists
Main article: Beta-1 adrenergic receptor#agonists
β1 agonists: stimulates adenylyl cyclase activity; opening of calcium channel.
(cardiac stimulants; used to treat cardiogenic shock, acute heart failure,
bradyarrhythmias). Selected examples are:




Dobutamine
Isoproterenol (β1 and β2)
Xamoterol
epinephrine
β2 agonists
Main article: Beta2-adrenergic agonist
β2 agonists: stimulates adenylyl cyclase activity; closing of calcium channel
(smooth muscle relaxants; used to treat asthma and COPD). Selected examples
are:













salbutamol (albuterol in USA)
Fenoterol
Formoterol
Isoproterenol (β1 and β2)
Metaproterenol
Salmeterol
Terbutaline
Clenbuterol
Isoetarine
pirbuterol
procaterol
ritodrine
epinephrin
Beta-adrenergic agonist
From Wikipedia, the free encyclopedia
Jump to: navigation, search
Beta-adrenergic agonists are adrenergic agonists which act upon the beta
receptors
β1 agonists
Main article: Beta-1 adrenergic receptor#agonists
β1 agonists: stimulates adenylyl cyclase activity; opening of calcium channel.
(cardiac stimulants; used to treat cardiogenic shock, acute heart failure,
bradyarrhythmias). Selected examples are:




Dobutamine
Isoproterenol (β1 and β2)
Xamoterol
epinephrine
β2 agonists
Main article: Beta2-adrenergic agonist
β2 agonists: stimulates adenylyl cyclase activity; closing of calcium channel
(smooth muscle relaxants; used to treat asthma and COPD). Selected examples
are:

salbutamol (albuterol in USA)










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
Fenoterol
Formoterol
Isoproterenol (β1 and β2)
Metaproterenol
Salmeterol
Terbutaline
Clenbuterol
Isoetarine
pirbuterol
procaterol
ritodrine
epinephrin
Mixed action


Ephedrine
Pseudoephedrine
Amphetamine (USAN) or amfetamine (INN) is a psychostimulant drug of the
phenethylamine class which produces increased wakefulness and focus in
association with decreased fatigue and appetite.
Brand names of medications that contain, or metabolize into, amphetamine
include Adderall, Dexedrine, Dextrostat, Desoxyn, ProCentra, and Vyvanse, as
well as Benzedrine in the past.
Physical effects of dextroamphetamine can include anorexia, hyperactivity,
dilated pupils, blood shot eyes, flushing, restlessness, dry mouth, bruxism,
headache, tachycardia, bradycardia, tachypnea, hypertension, hypotension,
fever, diaphoresis, diarrhea, constipation, blurred vision, aphasia, dizziness,
twitching, insomnia, numbness, palpitations, arrhythmias, tremors, dry and/or
itchy skin, acne, pallor, convulsions, and with chronic and/or high doses, seizure,
stroke, coma, heart attack and death can occur There is also significant research
which highlights the possible neurotoxic effects of amphetamine on the
dopaminergic system, even in clinical doses
Psychological effects
Psychological effects can include euphoria, anxiety, increased libido, alertness,
concentration, energy, self-esteem, self-confidence, sociability, irritability,
aggression, psychosomatic disorders, psychomotor agitation, grandiosity,
excessive feelings of power and superiority, repetitive and obsessive behaviors,
paranoia, and with chronic and/or high doses, amphetamine psychosis can
occur.[11][12]
Withdrawal effects
Withdrawal symptoms of amphetamine primarily consist of mental fatigue,
mental depression and an increased appetite. Symptoms may last for days with
occasional use and weeks or months with chronic use, with severity dependent on
the length of time and the amount of amphetamine used. Withdrawal symptoms
may also include anxiety, agitation, excessive sleep, vivid or lucid dreams, deep
REM sleep and suicidal ideation.[13][14][15]
Side effects
Contraindications
Amphetamine elevates cardiac output and blood pressure making it dangerous
for use by patients with a history of heart disease or hypertension. Amphetamine
can cause a life-threatening complication in patients taking MAOI
antidepressants. The use of amphetamine and amphetamine-like drugs is
contraindicated in patients with narrow-angle glaucoma or anatomically narrow
angles. Like other sympathomimetic amines, amphetamine can induce transient
mydriasis. In patients with narrow angles, pupillary dilation can provoke an
acute attack of angle-closure glaucoma. These agents should also be avoided in
patients with other forms of glaucoma, as mydriasis may occasionally increase
intraocular pressure. Amphetamine has been shown to pass through into breast
milk. Because of this, mothers taking amphetamine are advised to avoid
breastfeeding during their course of treatment
Dependence and addiction
Tolerance is developed rapidly in amphetamine abuse; therefore, periods of
extended use require increasing amounts of the drug in order to achieve the
same effect
Overdose
An amphetamine overdose is rarely fatal but can lead to a number of different
symptoms, including psychosis, chest pain, and hypertension.
Tyramine (4-Hydroxyphenethylamine; para-Tyramine; Mydrial, Uteramin) is
a naturally-occurring monoamine compound and trace amine derived from the
amino acid tyrosine.[1] Tyramine acts as a catecholamine (dopamine,
norepinephrine (noradrenaline), epinephrine (adrenaline)) releasing agent.
Notably, however, it is unable to cross the blood-brain-barrier (BBB), resulting
in only non-psychoactive peripheral sympathomimetic effects. When ingested
unintentionally from certain foods in conjunction with a monoamine oxidase
inhibitor (MAOI), tyramine is responsible for the so-called "cheese effect" often
seen with their use.
Occurrence
Tyramine occurs widely in plants and animals and is metabolized by the enzyme
monoamine oxidase. In foods, it is often produced by the decarboxylation of
tyrosine during fermentation or decay. Foods containing considerable amounts
of tyramine include meats that are potentially spoiled or pickled, aged, smoked,
fermented, or marinated (some fish, poultry, and beef); most pork
Physical effects and pharmacology
Physiologically metabolized by MAOA. In humans, if monoamine metabolism is
compromised by the use of monoamine oxidase inhibitors (MAOIs) and foods
high in tyramine are ingested, a hypertensive crisis can result as tyramine can
cause the release of stored monoamines, such as dopamine, norepinephrine,
epinephrine. The first signs of this were discovered by a neurologist who noticed
his wife, who at the time was on MAOI medication, had severe headaches when
eating cheese. For this reason, the crisis is still called the "cheese syndrome"
even though other foods can cause the same problem]. Most processed cheeses do
not contain high enough tyramine to cause hypertensive effects, although some
aged cheeses (such as Stilton cheese) do. A large dietary intake of tyramine (or a
dietary intake of tyramine while taking MAO inhibitors) can cause the 'tyramine
pressor response,' which is defined as an increase in systolic blood pressure of 30
mmHg or more. The displacement of norepinephrine (noradrenaline) from
neuronal storage vesicles by acute tyramine ingestion is thought to cause the
vasoconstriction and increased heart rate and blood pressure of the pressor
response. In severe cases, adrenergic crisis can occur.
However, if one has had repeated exposure to tyramine, there is a decreased
pressor response; tyramine is degraded to octopamine, which is subsequently
packaged in synaptic vesicles with norepinephrine (noradrenaline). Therefore,
after repeated tyramine exposure, these vesicles contain an increased amount of
octopamine and a relatively reduced amount of norepinephrine (noradrenaline).
When these vesicles are secreted upon tyramine ingestion, there is a decreased
pressor response, as less norepinephrine (noradrenaline) is secreted into the
synapse, and octopamine does not activate alpha or beta adrenergic receptors.
When using a MAO inhibitor (MAOI), the intake of approximately 10 to 25 mg
of tyramine is required for a severe reaction compared to 6 to 10 mg for a mild
reaction.
The possibility that tyramine acts directly as a neurotransmitter was revealed by
the discovery of a G protein-coupled receptor with high affinity for tyramine,
called TA1. The TA1 receptor is found in the brain as well as peripheral tissues,
including the kidney. The existence of a receptor with high affinity for tyramine
supports the hypothesis that tyramine may also act directly to affect blood
pressure regulation.
Dietary tyramine intake has also been associated with migraine in select
populations, leading many sufferers to restrict foods high in tyramine. Reports
on the tyramine-migraine link have been both affirmed and denied. A 2007
review published in Neurological Sciences[4] presented data showing that
migraine and cluster headaches are characterised by an increase of circulating
neurotransmitters and neuromodulators (including tyramine, octopamine and
synephrine) in the hypothalamus, amygdala and dopaminergic system.
Adrenergic antagonist
An Adrenergic antagonist is a pharmaceutical substance that acts to inhibit the
action of the adrenergic receptors. It is thus a type of sympatholytic.
It has the opposite effect as adrenergic agonists.
More specifically, they can be divided into:


Alpha blockers
Beta blockers
Alpha blocker
α blockers or (adrenergic) α-antagonists are pharmacological agents that act as
antagonists of α adrenergic receptors (α-adrenoceptors).[1]
Classification


α1 blockers or antagonists act at α1-adrenoceptors
α2 blockers or antagonists act at α2-adrenoceptors
When the term "alpha blocker" is used without further qualification, it
sometimes refers to α1 blockers, and sometimes refers to agents that act at both
types of receptorsGuanfacine, Clonidine and Prazosin are examples of Alpha
Blockers.
Non-selective α-adrenergic blockers include:


Phenoxybenzamine
Phentolamine .
Uses
α blockers are used in the treatment of several conditions, such as Raynaud's
disease, hypertension, and scleroderma.[2]
Alpha Blockers can also be used to treat anxiety and panic, such as Generalized
Anxiety Disorder, Panic Disorder or PTSD. Alpha2-adrenergic receptor
agonists, such as clonidine and guanfacine, act at noradrenergic autoreceptors to
inhibit the firing of cells in the locus ceruleus, effectively reducing the release of
brain norepinephrine (3). Clonidine has shown promise among patients with
Anxiety, Panic and PTSD in clinical trials and was used to treat severely and
chronically abused and neglected preschool children. It improved disturbed
behavior by reducing aggression, impulsivity, emotional outbursts, and
oppositionality (4). Insomnia and nightmares were also reported to be reduced.
Kinzie and Leung (5) prescribed the combination of clonidine and imipramine to
severely traumatized Cambodian refugees with Anxiety, Panic and PTSD.
Global symptoms of PTSD were reduced among sixty-six percent and
nightmares among seventy-seven percent. Guanfacine produces less sedation
than clonidine and thus may be better tolerated. Guanfacine reduced the
trauma-related nightmares (6). A recently completed randomized double-blind
trial among veteran patients with chronic PTSD showed that augmentation with
guanfacine was associated with improvement in anxiety and PTSD.nightmares,
as well as overall Anxiety and PTSD symptoms.
Beta blocker
Beta blockers (sometimes written as β-blockers) or beta-adrenergic blocking
agents, beta-adrenergic antagonists, or beta antagonists, are a class of drugs used
for various indications, but particularly for the management of cardiac
arrhythmias, As beta adrenergic receptor antagonists, they diminish the effects
of epinephrine (adrenaline), significant use of beta blockers with propranolol
and pronethalol; it revolutionized the medical management of angina pectoris[5]
and is considered by many to be one of the most important contributions to
clinical medicine and pharmacology of the 20th century
Beta blockers block the action of endogenous catecholamines (epinephrine
(adrenaline) and norepinephrine (noradrenaline) in particular), on β-adrenergic
receptors, part of the sympathetic nervous system which mediates the "fight or
flight" response.[7][8] There are three known types of beta receptor, designated β1,
β2 and β3 receptors.[9] β1-adrenergic receptors are located mainly in the heart and
in the kidneys.[8] β2-adrenergic receptors are located mainly in the lungs,
gastrointestinal tract, liver, uterus, vascular smooth muscle, and skeletal
muscle.[8] β3-adrenergic receptors are located in fat cells.[10]
β-Receptor antagonism
Stimulation of β1 receptors by epinephrine induces a positive chronotropic and
inotropic effect on the heart and increases cardiac conduction velocity and
automaticity Stimulation of β1 receptors on the kidney causes renin release.
Stimulation of β2 receptors induces smooth muscle relaxation, induces tremor in
skeletal muscle and increases glycogenolysis in the liver and skeletal muscle
Stimulation of β3 receptors induces lipolysis.
Beta blockers inhibit these normal epinephrine-mediated sympathetic actions
but have minimal effect on resting subjects]. That is, they reduce
excitement/physical exertion on heart rate and force of contraction,] and also
tremo and breakdown of glycogen, but increase dilation of blood vessels] and
constriction of bronchi.
It is therefore expected that non-selective beta blockers have an antihypertensive
effect The primary antihypertensive mechanism of betablockers is unclear but it
may involve reduction in cardiac output (due to negative chronotropic and
inotropic effects It may also be due to reduction in renin release from the
kidneys, and a central nervous system effect to reduce sympathetic activity (for
those β-blockers that do cross the blood-brain barrier, e.g. Propranolol).
Antianginal effects result from negative chronotropic and inotropic effects,
which decrease cardiac workload and oxygen demand. Negative chronotropic
properties of beta blockers allow the lifesaving property of heart rate control.
Beta blockers are readily titrated to optimal rate control in many pathologic
states.
The antiarrhythmic effects of beta blockers arise from sympathetic nervous
system blockade – resulting in depression of sinus node function and
atrioventricular node conduction, and prolonged atrial refractory periods.
Sotalol, in particular, has additional antiarrhythmic properties and prolongs
action potential duration through potassium channel blockade.
Blockade of the sympathetic nervous system on renin release leads to reduced
aldosterone via the renin angiotensin aldosterone system with a resultant
decrease in blood pressure due to decreased sodium and water retention.
Intrinsic sympathomimetic activity
Also referred to as intrinsic sympathomimetic effect, this term is used
particularly with beta blockers that can show both agonism and antagonism at a
given beta receptor, depending on the concentration of the agent (beta blocker)
and the concentration of the antagonized agent (usually an endogenous
compound such as norepinephrine). See partial agonist for a more general
description.
Some beta blockers (e.g. oxprenolol, pindolol, penbutolol and acebutolol) exhibit
intrinsic sympathomimetic activity (ISA). These agents are capable of exerting
low level agonist activity at the β-adrenergic receptor while simultaneously
acting as a receptor site antagonist. These agents, therefore, may be useful in
individuals exhibiting excessive bradycardia with sustained beta blocker
therapy.
Agents with ISA are not used in post-myocardial infarction as they have not been
demonstrated to be beneficial. They may also be less effective than other beta
blockers in the management of angina and tachyarrhythmia.[23]
α1-Receptor antagonism
Some beta blockers (e.g. labetalol and carvedilol) exhibit mixed antagonism of
both β- and α1-adrenergic receptors, which provides additional arteriolar
vasodilating action.
Other effects
Beta blockers decrease nocturnal melatonin release, perhaps partly accounting
for sleep disturbance caused by some agents. Beta blockers protect against social
anxiety] "Improvement of physical symptoms has been demonstrated with betablockers such as propranolol; however, these effects are limited to the social
anxiety experienced in performance situations] (example: an inexperienced
symphony soloist)
They can also be used to treat glaucoma because they decrease intraocular
pressure by lowering aqueous humor secretion.
Clinical use
Large differences exist in the pharmacology of agents within the class, thus not
all beta blockers are used for all indications listed below.
Indications for beta blockers include:
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Angina pectoris
Atrial fibrillation
Cardiac arrhythmia
Congestive heart failure
Essential tremor
Glaucoma
Hypertension
Migraine prophylaxis
Mitral valve prolapse
Myocardial infarction
Phaeochromocytoma, in conjunction with α-blocker
Symptomatic control (tachycardia, tremor) in anxiety and
hyperthyroidism
Beta blockers have also been used in the following conditions:
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Acute aortic dissection
Hypertrophic obstructive cardiomyopathy
Marfan syndrome (treatment with propranolol slows progression of
aortic dilation and its complications)
Prevention of variceal bleeding in portal hypertension
Possible mitigation of hyperhidrosis
Social anxiety disorder and other anxiety disorders
Congestive heart failure
Although beta blockers were once contraindicated in congestive heart failure, as
they have the potential to worsen the condition, studies in the late 1990s showed
their efficacy at reducing morbidity and mortality in congestive heart failure.
Bisoprolol, carvedilol and sustained-release metoprolol are specifically indicated
as adjuncts to standard ACE inhibitor and diuretic therapy in congestive heart
failure.
Beta blockers are primarily known for their reductive effect on heart rate,
although this is not the only mechanism of action of importance in congestive
heart failure]. Beta blockers, in addition to their sympatholytic B1 activity in the
heart, influence the renin/angiotensin system at the kidneys. Beta blockers cause
a decrease in renin secretion, which in turn reduce the heart oxygen demand by
lowering extracellular volume and increasing the oxygen carrying capacity of
blood. Beta blockers sympatholytic activity reduce heart rate, thereby increasing
the ejection fraction of the heart despite an initial reduction in ejection fraction.
Trials have shown that beta blockers reduce the absolute risk of death by 4.5%
over a 13 month period. As well as reducing the risk of mortality, the number of
hospital visits and hospitalizations were also reduced in the trials.
Anxiety and performance enhancement
There is clear evidence from many controlled trials in the past 25 years that beta
blockers are effective in anxiety disorders, though the mechanism of action is not
known. Some people have used beta blockers for performance enhancement, and
especially to combat 'performance anxiety'. In particular, musicians, public
speakers, actors, and professional dancers, have been known to use beta blockers
to avoid stage fright and tremor during public performance and especially
auditions. The physiological symptoms of the fight/flight response associated
with performance anxiety and panic (pounding heart, cold/clammy hands,
increased respiration, sweating, etc.) are significantly reduced, thus enabling
anxious individuals to concentrate on the task at hand. Stutterers also use beta
blockers to avoid fight/flight responses, hence reducing the tendency to stutter.
Since they promote a lower heart rate and reduce tremor, beta blockers have
been used by some Olympic marksmen to enhance performance, though beta
blockers are banned by the International Olympic Committee (IOC). Although
they have no recognisable benefit to most sports, it is acknowledged that they are
beneficial to sports such as archery and shooting. A recent, high-profile
transgression took place in the 2008 Summer Olympics, where 50 metre pistol
silver medallist and 10 metre air pistol bronze medallist Kim Jong-su tested
positive for propranolol and was stripped of his medal.