DOPAMINE

Outside the central nervous system, dopamine functions in several parts of the peripheral nervous
system as a local chemical messenger. In blood vessels, it inhibits norepinephrine release and acts
as a vasodilator (at normal concentrations); in the kidneys, it increases sodium excretion and urine
output; in the pancreas, it reduces insulin production; in the digestive system, it
reducesgastrointestinal motility and protects intestinal mucosa; and in the immune system, it
reduces the activity of lymphocytes. With the exception of the blood vessels, dopamine in each of
these peripheral systems is synthesized locally and exerts its effects near the cells that release it.
Several important diseases of the nervous system are associated with dysfunctions of the dopamine
system, and some of the key medications used to treat them work by altering the effects of
dopamine. Parkinson's disease, a degenerative condition causing tremor and motor impairment, is
caused by a loss of dopamine-secreting neurons in an area of the midbrain called the substantia
nigra. Its metabolic precursor L-DOPA can be manufactured, and in its pure form marketed
as Levodopa is the most widely used treatment for the condition. There is evidence
that schizophrenia involves altered levels of dopamine activity, and most antipsychotic drugs used to
treat this are dopamine antagonists which reduce dopamine activity.[2] Similar dopamine antagonist
drugs are also some of the most effective anti-nausea agents. Restless legs syndrome and attention
deficit hyperactivity disorder (ADHD) are associated with decreased dopamine activity.
[3]

Dopaminergic stimulants can be addictive in high doses, but some are used at lower doses to treat

ADHD. Dopamine itself is available as a manufactured medication for intravenous injection: although
it cannot reach the brain from the bloodstream, its peripheral effects make it useful in the treatment
of heart failure or shock, especially in newborn babies.

Targets

system-wide

Receptors

D1, D2, D3, D4, D5, TAAR1[1]

Agonists

Direct: apomorphine,bromocryptine
Indirect: cocaine, amphetamines

Antagonists

neuroleptics, metoclopramide,domperidone

Precursor

Phenylalanine, Tyrosine, and L-DOPA

Synthesizing

DOPA decarboxylase

enzyme

Metabolizing

MAO, COMT[1]

enzyme

EFEDRINA
Ephedrine is a medication used to prevent low blood pressure during spinal anesthesia.[1] It has also
been used for asthma,narcolepsy, and obesity but is not the preferred treatment. It can be taken by
mouth or by injection into a muscle, vein, or just under the skin. Onset with intravenous use is fast,
while injection into a muscle can take 20 minutes, and by mouth can take an hour for effect. When
given by injection it lasts about an hour and when taken by mouth it can last up to four hours. [1]
Common side effects include trouble sleeping, anxiety, headache, hallucinations, high blood
pressure, fast heart rate, loss of appetite, and inability to urinate. Serious side effects
include stroke, heart attack, and abuse.[1] While likely safe in pregnancy its use in this population is
poorly studied.[2][3] Use during breastfeeding is not recommended.[3] Ephedrine works by turning on
and adrenergic receptors.[1]

NORADRENALINE
The general function of norepinephrine is to mobilize the brain and body for action. Norepinephrine
release is lowest during sleep, rises during wakefulness, and reaches much higher levels during
situations of stress or danger, in the so-called fight-or-flight response. In the brain, norepinephrine
increases arousal and alertness, promotes vigilance, enhances formation and retrieval of memory,
and focuses attention; it also increases restlessness and anxiety. In the rest of the body,
norepinephrine increases heart rate and blood pressure, triggers the release of glucose from energy
stores, increases blood flow to skeletal muscle, reduces blood flow to the gastrointestinal system,
and inhibits voiding of the bladder and gastrointestinal motility.
A variety of medically important drugs work by altering the actions of norepinephrine
systems. Norepinephrine itself is widely used as an injectable drug for the treatment of critically low
blood pressure. Beta blockers, which counter some of the effects of norepinephrine, are frequently
used to treat glaucoma, migraine, and a range of cardiovascular problems. Alpha blockers, which
counter a different set of norepinephrine effects, are used to treat several cardiovascular and
psychiatric conditions. Alpha-2 agonistsoften have a sedating effect, and are commonly used as

anesthesia-enhancers in surgery, as well as in treatment of drug or alcohol dependence. Many

important psychiatric drugs exert strong effects on norepinephrine systems in the brain, resulting in
side-effects that may be helpful or harmful.

FENILEFRINE
Medical uses[edit]

Decongestant[edit]
Phenylephrine is used as a decongestant sold as an oral medicine or as a nasal spray. It is a
common ingredient in over-the-counterdecongestants. Other decongestants
include oxymetazoline and pseudoephedrine.
Phenylephrine is used as an alternative for pseudoephedrine in decongestant medicines due to
pseudoephedrine's use in the illicit manufacture of methamphetamine. Its efficacy as an oral
decongestant has been questioned, with multiple studies not being able to come to an agreement. [1][2]
Pharmacists Leslie Hendeles and Randy Hatton of the University of Florida suggested in 2006 that
oral phenylephrine is ineffective as a decongestant at the 10-mg dose used, arguing that the studies
used for the regulatory approval of the drug in the United States in 1976 were inadequate to prove
effectiveness at the 10-mg dose, and safety at higher doses. [4]
A 2007 meta-analysis by Hatton et al. concluded that the evidence for its effectiveness is insufficient,
[5]

though another meta-analysis published shortly thereafter by researchers

from GlaxoSmithKline found the standard 10-mg dose to be significantly more effective than a
placebo; however, the fact that GSK markets many products containing phenylephrine has raised
some speculation regarding selective publishing and other controversial techniques. [6] A 2007 study
by Wyeth Consumer Healthcare notes that 7 studies available in 1976 support the efficacy of
phenylephrine at a 10 mg dosage.[7]
Two studies published in 2009 examined the effects of phenylephrine on symptoms of allergic
rhinitis by exposing sufferers to pollen in a controlled, indoor environment. Neither study was able to
distinguish between the effects of phenylephrine or a placebo. Pseudoephedrine and loratadinemontelukast therapy were found to be significantly more effective than both phenylephrine and
placebo.[1][2]
The Food and Drug Administration has stood by its 1976 approval of phenylephrine for nasal
congestion as the debate continues.[8]

Hemorrhoids[edit]
Hemorrhoids are caused by swollen veins in the rectal area.[9] Phenylephrine can be used topically to
prevent symptoms of hemorrhoids. Phenylephrine causes the constriction of vascular smooth
muscle and is often used in the treatment of hemorrhoids presumably to narrow the swollen veins

and relieve the attendant pain. However, veins--unlike arteries--contain less vascular smooth muscle
in their walls so the mechanism by which pain relief is achieved is likely related to something other
than vascular change alone. Products for treatment may also include substances that will form a
protective barrier over the inflamed area, resulting in less pain when faeces are passed.[10]

Pupil dilatation[edit]
Phenylephrine is used as an eye drop to dilate the pupil to facilitate visualization of the retina. It is
often used in combination with tropicamide as a synergist when tropicamide alone is not sufficient.
Narrow-angle glaucoma is a contraindication to phenylephrine use. As a mydriatic, it is available in
2.5% and 10% minims. Phenylephrine eye drops are applied to the eye after a topical anestheic is
applied.[11]

Vasopressor[edit]
Phenylephrine is commonly used as a vasopressor to increase the blood pressure in unstable
patients with hypotension, especially resulting from septic shock. Such use is common in anesthesia
or critical-care practices; it is especially useful in counteracting the hypotensive effect
of epidural and subarachnoid anesthetics, as well as the vasodilating effect of bacterial toxins and
the inflammatory response in sepsis and systemic inflammatory response syndrome. The elimination
half life of phenylephrine is about 2.5 to 3.0 hours.[12] The clinical effects of a single intravenous bolus
dose of phenylephrine are short lived and needs to be repeated every 1015 minutes. Commonly
the drug is given as a carefully titrated intravenous infusion with a syringe pump or volumetric pump.
Because of its vasoconstrictive effect, phenylephrine can cause severe necrosis if it infiltrates the
surrounding tissues. Because of this, it should be given through a central line if at all possible.
Damage may be prevented or mitigated by infiltrating the tissue with the alpha blocker phentolamine
by subcutaneous injection.[13]
Phenylephrine hydrochloride at 0.25% is used as a vasoconstrictor in
some suppository formulations.[14]

Priapism[edit]
Phenylephrine is used by urologists to abort priapism. It is diluted with normal saline and injected
directly into the corpora cavernosa. The mechanism of action is to cause constriction of the blood
vessels entering into the penis, thus causing decreased blood flow and relieving the priapism. An
injection is given every 35 minutes. If priapism is not resolved in 1 hour, another form of therapy is
considered.[15]

Side effects[edit]
Heart[edit]

The primary side effect of phenylephrine is high blood pressure. People with high blood pressure are
typically advised to avoid products containing it. Because this medication is
asympathomimetic amine without beta-adrenergic activity, it does not increase contractility force and
output of the cardiac muscle. It may increase blood pressure resulting in a slow heart rate through
stimulation of vascular (likely carotid) baroreceptors. A common side effect during IV administration
is reflex bradycardia.[16] The low concentration eye drops do not cause blood pressure changes and
the changes with the higher dose drops do not last long.[17]

Other[edit]
Prostatic hyperplasia can also be worsened by use, and chronic use can lead to rebound hyperemia.
[18]

People with a history of anxiety or panic disorders, or on anticonvulsant medication for epilepsy

should not take this substance. The drug interaction might produce seizures. Some patients have
been shown to have an upset stomach, severe abdominal cramping, and vomiting issues connected
to taking this drug.[19]
Phenylephrine is pregnancy category C. Due to the lack of studies done in animals and in humans, it
is not known whether there is harm to the fetus. Phenylephrine should only be given to pregnant
women who have a clear need.[19]
Extended use may cause rhinitis medicamentosa, a condition of rebound nasal congestion.[20]

Interactions[edit]
The increase in blood pressure effect of phenylephrine may be increased by drugs such
as monoamine oxidase inhibitors, tricyclic antidepressants, and hydrocortisone. Patients taking
these medications may need a lower dose of phenylephrine to achieve a similar increase in blood
pressure.
Drugs that may decrease the effects of phenylephrine may include calcium channel blockers, ACE
inhibitors and benzodiazepines. Patients taking these medications may need a higher dose of
phenylephrine to achieve a comparable increase in blood pressure.[21]

Mechanism of action[edit]
Oral phenylephrine is extensively metabolized by monoamine oxidase,[22] an enzyme that is present
on the outside of cells, throughout the body.[23] Compared to intravenous pseudoephedrine,
phenylephrine has a reduced and variable bioavailability; only up to 38%.[22][24] Phenylephrine is a
sympathomimetic drug, which means that it mimics the actions of epinephrine (commonly known as
adrenaline) or norepinephrine. Phenylephrine selectively binds to alpha receptors which cause blood
vessels to constrict. Phenylephrine may cause side effects such as headache, reflex bradycardia,
excitability, restlessness and cardiac arrhythmias. Phenylephrine is not suggested for use in patients
with hypertension.[25]

Whereas pseudoephedrine causes both vasoconstriction and increase of mucociliary

clearance through its nonspecific adrenergic activity, phenylephrine's selective -adrenergic agonism
causes vasoconstriction alone, creating a difference in their methods of action.

METARAMINOL
Metaraminol (INN; trade names Aramine, Metaramin, and Pressonex), also known
as metaradrine, a stereoisomer of meta-hydroxynorephedrine (3,-dihydroxyamphetamine), is a
potent sympathomimetic amine used in the prevention and treatment ofhypotension, particularly as a
complication of anesthesia. It is an 1-adrenergic receptor agonist with some effect.[1]
Metaraminol is also used in the treatment of priapism. Although not approved for this use, it appears
to be effective.
METHOXAMINE
Methoxamine Hydrochloride is an 1-adrenergic receptor agonist,[1] SNRI, MDMA agonist
somewhat similar in structure tobutaxamine and 2,5-DMA. It was first theorised and synthesised by
British pharmacologist Oliver Ansell in 2015 and then patented on January 4th 2016. The compound
has been accepted for preliminary clinical trials.[2] Methoxamine is a theoretical novel fastactingantidepressant with mood lifting qualities that may alleviate the symptoms of clinical
depression as an ultra-fast onset agent, in comparison to SSRIs, MAOIs and
even tricyclic and tetracyclic antidepressants. Which all have a significantly long period of time for
the optimum peak blood concentration is attained, commonly leading to patients to discontinue their
treatment and can also inducesuicidal ideation.
This is not the case with Methoxamine, as it readily crosses the blood brain barrier and stimulates
the release of serotonin, inhibits the re-uptake of norepinephrine. Mood lift is also expected to be
enhanced by the M1 metabolite, which weakly binds to -opioid receptors (approximate potency is
comparable of that of dextropropoxyphene.but at proper prescribed doses and time frames there is a
very low risk of this causing any dependency or tolerance to the effect)
For example, a standard sublingual dose of 15mg would be equipotent between 5-25mg
of dextropropoxyphene depending on the metabolism of the individual. Although this in no way
implies that methoxamine or its metabolites resemble dextropropoxyphene, it is simply a
weak opioid from which an easy comparison can be drawn.
The drug occasionally induces slight vasoconstriction of skin and splanchnic blood vessels, thereby
increasing peripheral vascular resistance and raising mean arterial blood pressure. Because of its
hypertensive effects, it may evoke a compensatory reflexbradycardia via the baroreceptors.

CLONIDINE
The US Food and Drug Administration (FDA) has approved clonidine for the treatment ofattention
deficit hyperactivity disorder (ADHD), alone or with stimulants in 2010, for pediatric patients aged 6
17 years.[2][6] It was later approved for adults. In Australia, clonidine is an accepted but not approved
use for ADHD by the TGA.[7] Clonidine along with methylphenidatehas been studied for treatment
of ADHD.[8][9][10] According to the clinical trials submitted to FDA its effectiveness is comparable to
stimulants commonly used for ADHD. When used alone it leads to ~35% improvement in symptoms,
comparable to ~30% improvement when stimulants are used.[11][12] Some studies show clonidine more
sedating than guanfacine, which may be better at bed time along with an arousing stimulant at
morning.[13][14] Clonidine can be used in the treatment of Tourette syndrome (specifically for tics).
[15]

Clonidine may be used to ease withdrawal symptoms associated with the long-term use

of narcotics, alcohol, benzodiazepine and nicotine (smoking).[16] It can alleviate opioid withdrawal
symptoms by reducing the sympathetic nervous system response such
as tachycardia and hypertension, as well as reducing sweating, hot and cold flashes, and general
restlessness.[17] It may also be helpful in aiding smokers to quit.[18] The sedation effect is also useful
although its side effects can include insomnia, thus exacerbating an already common feature of
opioid withdrawal.[19]
Clonidine also has several off-label uses, and has been prescribed to treat psychiatric
disorders including stress, sleep disorders, and hyperarousal caused by post-traumatic stress
disorder, borderline personality disorder, and other anxietydisorders.[20][21][22][23][24][25][26][27] Clonidine is also
a mild sedative, and can be used as premedication before surgery or procedures.[28] Its epidural use
for pain during heart attack, postoperative and intractable pain has also been studied extensively.
[29]

Clonidine has also been suggested as a treatment for rare instances

of dexmedetomidine withdrawal.[30] Clonidine can be used inrestless legs syndrome. It can also be
used to treat facial flushing and redness associated with rosacea.[31] It has also been successfully
used topically in a clinical trial as a treatment for diabetic neuropathy.[32] Clonidine can also be used
for migraineheadaches and hot flashes associated with menopause.[33][34] Clonidine has also been
used to treat diarrhea associated with irritable bowel syndrome, fecal incontinence, diabetes,
withdrawal-associated diarrhea, intestinal failure, neuroendocrine tumors and cholera. [35]

METILDOPA
Methyldopa (L--Methyl-3,4-dihydroxyphenylalanine; Aldomet, Aldoril, Dopamet, Dopegyt, etc.)
is a centrally acting antihypertensive agent. It is metabolized to alpha-methylnorepinephrine in the
brain, and this compound is thought to activate central alpha-2 adrenergic receptors (Gerber, 1990).
Being a selective agonist for 2 adrenergic receptors, psychoactive drug is used as
asympatholytic or antihypertensive. Its use is now mostly deprecated following the introduction of
alternative safer classes of agents. However, it continues to have a role in otherwise difficult to

treat hypertension and gestational hypertension (previously known as pregnancy-induced

hypertension (PIH)).
TOLAZOLINE
Tolazoline is a non-selective competitive -adrenergic receptor antagonist. It is a vasodilator that is
used to treat spasms of peripheral blood vessels (as in acrocyanosis). It has also been used (in
conjunction with Sodium nitroprusside) successfully as an antidote to reverse the severe peripheral
vasoconstriction which can occur as a result of overdose with certain 5-HT2A agonist drugs such
as 25I-NBOMe,[citation needed] DOB and Bromodragonfly (prolonged severe vasoconstriction can lead
to gangrene if untreated).[1][2]
It is however most commonly used in veterinary medicine, to reverse xylazine-induced sedation.

PHENTOLAMINE
Mechanism[edit]
Its primary action is vasodilation due to 1 blockade.[3]
Non-selective -blockers can cause a much more pronounced reflex tachycardia than the
selective -1 blockers. Like the selective -1 blockers, phentolamine causes a relaxation of systemic
vasculature, leading to hypotension. This hypotension is sensed by thebaroreceptor reflex, which
results in increased sympathetic nerve firing on the heart, releasing norepinephrine. In response,
the -1 adrenergic receptors on the heart increase its rate, contractility, and dromotropy, which help
to offset the decrease in systemic blood pressure. Unlike the -1 selective blockers, phentolamine
also inhibits the 2 receptors, which function predominantly as presynapticnegative feedback for
norepinephrine release. By abolishing this negative feedback phentolamine leads to even less
regulated norepinephrine release, which results in a more drastic increase in heart rate. [4]

Uses[edit]
The primary application for phentolamine is for the control of hypertensive emergencies, most
notably due to pheochromocytoma. [5]
It also has usefulness in the treatment of cocaine-induced cardiovascular complications, where one
would generally avoid Beta-blockers (e.g. metoprolol), as they can cause unopposed alphaadrenergic mediated coronary vasoconstriction, worsening myocardial ischemia and hypertension. It
is important to note that phentolamine is not a first-line agent for this indication. Phentolamine should
only be given to patients who do not fully respond to benzodiazepines, nitroglycerin, and calcium
channel blockers. [6][7]

When given by injection it causes blood vessels to dilate, thereby increasing blood flow. When
injected into the penis (intracavernosal), it increases blood flow to the penis, which results in an
erection.[8]
It may be stored in crash carts to counteract severe peripheral vasoconstriction secondary
to extravasation of peripherally placedvasopressor infusions, typically
of norepinephrine. Epinephrine infusions are less vasoconstrictive than norepinephrine as they
primarily stimulate beta receptor more than alpha receptors, but the effect remains dose dependent.
Phentolamine also has diagnostic and therapeutic roles in complex regional pain syndrome (reflex
sympathetic dystrophy).[9]
Phentolamine has recently been introduced in the dental field as a local anesthetic reversal agent.
Distributed by Septodont,OraVerse is a Phentolamine Mesylate injection designed to reverse the
local vasoconstrictor properties used in many local anesthetics to prolong anesthesia. [10] OraVerse
has been shown to accelerate the reversal of the lingering soft-tissue numbness associated with the
widely used anesthetic-vasoconstrictor combinations. [11]
PRAZOSIN
Prazosin, trade names Minipress, Vasoflex, Lentopres and Hypovase, is a sympatholytic drug
used to treat high blood pressure and anxiety, PTSD, and panic disorder. It is an alpha-adrenergic
blocker that is specific for the alpha-1 receptors. These receptors are found on vascular smooth
muscle, where they are responsible for the vasoconstrictive action of norepinephrine. They are also
found throughout the central nervous system.[1] As of 2013, prazosin is off-patent in the US, and the
FDA has approved at least one generic manufacturer.
In addition to its alpha-blocking activity, prazosin is an antagonist of the MT3 receptor (which is not
present in humans), with selectivityfor this receptor over the MT1 and MT2 receptors.[2]
4-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-1-piperazinyl](2-furyl)methanone

Medical use[edit]
Prazosin is orally active and has a minimal effect on cardiac function due to its alpha-1
receptor selectivity. However, when prazosin is started, heart rate and contractility go up in order to
maintain the pre-treatment blood pressures because the body has reachedhomeostasis at its
abnormally high blood pressure. The blood pressure lowering effect becomes apparent when
prazosin is taken for longer periods of time. The heart rate and contractility go back down over time
and blood pressure decreases.

The antihypertensive characteristics of prazosin make it a second-line choice for the treatment of
high blood pressure.[3]
Prazosin is also useful in treating urinary hesitancy associated with prostatic hyperplasia, blocking
alpha-1 receptors, which control constriction of both the prostate and urethra. Although not a first line
choice for either hypertension or prostatic hyperplasia, it is a choice for patients who present with
both problems concomitantly.[3]
This medication has shown to be effective in treating severe nightmares in children and people with
PTSD symptoms.[4] Veterans have also been treated successfully at Seattle's VA Puget Sound Health
Care System (VAPSHCS) for sleep disturbance related to PTSD. Doses are lower for this purpose
than for control of blood pressure.[4]
TERAZOSIN
Terazosin (marketed as Hytrin or Zayasel) is a selective alpha-1 antagonist used for treatment of
symptoms of an enlarged prostate(BPH). It also acts to lower the blood pressure, and is therefore a
drug of choice for men with hypertension and prostate enlargement. It is available in 1 mg, 2 mg,
5 mg or 10 mg doses.[1]
It works by blocking the action of adrenaline on smooth muscle of the bladder and the blood
vessel walls.
Most common side effects include dizziness, drowsiness, headache, constipation, loss of appetite,
fatigue, nasal congestion or dry eyes, but they generally go away after only a few days of use.
Therapy should always be started with a low dose to avoid first dose phenomenon.[2] Sexual side
effects are rare, but may include priapism or erectile dysfunction.

Systematic (IUPAC) name

RS)-6,7-dimethoxy-2-[4-(tetrahydrofuran-2-ylcarbonyl)piperazin-1-yl]quinazolin-4-amine

SALMETEROL
Salmeterol is a long-acting 2 adrenergic receptor agonist (LABA) used in the maintenance and
prevention of asthma symptoms and maintenance of chronic obstructive pulmonary disease (COPD)
symptoms.[1] Symptoms of bronchospasm include shortness of breath,wheezing, coughing and chest
tightness. It is also used to prevent breathing difficulties during exercise (exercise-induced
bronchoconstriction).[2] It is marketed as Serevent in the US.[3] It is available as a dry powder
inhaler that releases a powdered form of the drug. It was previously available as a metered-dose
inhaler (MDI) but was discontinued in the US in 2002.[1][4] It is still available as an MDI in the UK as of
2013.
RS)-2-(hydroxymethyl)-4-{1-hydroxy-2-[6-(4-phenylbutoxy)hexylamino]ethyl}phenol

ALBETUROL

Salbutamol, also known as albuterol and marketed as Ventolin among other names,[1] is a
medication that opens up the medium and large airways in the lungs.[3] It is used to
treat asthma, exercise-induced bronchospasm, and chronic obstructive pulmonary disease (COPD).
[3]

It may also be used to treat high blood potassium levels.[4] It is usually used

by inhaler or nebulizer but is also available as a pill and intravenous solution.[3][5] Onset of action of
the inhaled version is typically within 15 minutes and lasts for two to six hours. [3]
Common side effects include shakiness, headache, fast heart rate, dizziness, and feeling anxious.
Serious side effects may include worsening bronchospasm, irregular heartbeat, and low blood
potassium levels.[3] It can be used during pregnancy and breastfeeding, but safety is not entirely
clear.[3][6] Salbutamol is a short-acting 2 adrenergic receptor agonist which works by causing
airway smooth muscles to relax.[3]
Salbutamol was first made in 1967 in Britain.[7] It was approved for medical use in the United States
in 1982.[3] It is on the World Health Organization's List of Essential Medicines, the most important
medication needed in a basic health system.[8] It is available as ageneric medication.[3] The wholesale
cost of an inhaler which contains 200 doses is between $1.12 and $2.64 (USD) as of 2014. [9] In the
United States it is between $25 and $50 for a typical month supply.[10]
(RS)-4-[2-(tert-Butylamino)-1-hydroxyethyl]-2-(hydroxymethyl)phenol
ORCIPRENALINE

Orciprenaline (INN), also known as metaproterenol (USAN), is a bronchodilator used in the

treatment of asthma.[1][2] Orciprenaline is a moderately selective 2 adrenergic receptor agonist that
stimulates receptors of the smooth muscle in the lungs, uterus, and vasculature supplying skeletal
muscle, with minimal or no effect on adrenergic receptors. The pharmacologic effects of
adrenergicagonist drugs, such as orciprenaline, are at least in part attributable to stimulation through
adrenergic receptors of intracellularadenylyl cyclase, the enzyme which catalyzes the conversion
of ATP to cAMP. Increased cAMP levels are associated with relaxation of bronchial smooth muscle
and inhibition of release of mediators of immediate hypersensitivity from many cells, especially from
mast cells.
(RS)-5-[1-hydroxy-2-(isopropylamino)ethyl]benzene-1,3-diol

TERBUTALINE

Terbutaline (trade names "Bronclyn",Brethine, Bricanyl, Brethaire, or Terbulin) is a 2 adrenergic

receptor agonist, used as a "reliever" inhaler in the management of asthma symptoms and as
a tocolytic (anti-contraction medication) to delay preterm labor for up to 48 hours. This time can then
be used to administer steroid injections to the mother which help fetal lung maturity and reduce
complications of prematurity.[1] It should not be used to prevent preterm labor or delay labor more
than 4872 hours. In February 2011, the Food and Drug Administration has ordered to put a boxed
warning on the drug's label. Pregnant women should not be given injections of the drug terbutaline
for the prevention of preterm labor or for long-term (beyond 4872 hours) management of preterm
labor, and should not be given oral terbutaline for any type of prevention or treatment of preterm
labor "due to the potential for serious internal heart problems and death." [2][3]
The American College of Obstetricians and Gynecologists also discourages the use of terbutaline for
preventing preterm labor.
Terbutaline is currently on the World Anti-Doping Agency's list of prohibited drugs, except when
administered by inhalation and a Therapeutic Use Exemption (TUE) has been obtained in advance.

Uses[edit]
Terbutaline is used as a fast-acting bronchodilator (often used as a short-term asthma treatment)
and as a tocolytic[4] to delaypremature labor. The inhaled form of terbutaline starts working within 15
minutes and can last up to 6 hours.
Terbutaline as a treatment for premature labor is an off-label use not approved by the FDA. It is
a pregnancy category C medication and is routinely prescribed to stop contractions. After successful
intravenous tocolysis, little evidence exists that oral terbutaline is effective. [5] However, following
uterine inversion in the third stage of labor, terbutaline (or either Halothane or magnesium sulfate)
can be used to relax the uterus if necessary prior to uterine replacement.
RS)-5-[2-(tert-butylamino)-1-hydroxyethyl]benzene-1,3-diol

ISOPRENALINE

Isoprenaline (INN) or isoproterenol (USAN) (trade names Medihaler-Iso and Isuprel) is

a medication used for the treatment ofbradycardia (slow heart rate), heart block, and rarely
for asthma. In humans, it is a non-selective adrenoreceptor agonist andTAAR1 agonist that is
structurally similar to epinephrine (adrenaline).[1][2]
Uses[edit]
Its primary use is for bradycardia or heart block. By activating 1 adrenergic receptor in the heart, it
induces positive chronotropic,dromotropic, and inotropic effects.[2]
It can be used as an inhaled aerosol to treat asthma, although this is currently a rare treatment.
[2]

Although it activates all betaadrenergic receptors, it works in a similar fashion to

selective 2 adrenergic agonists, e.g. salbutamol, by relaxing the airways to increase airflow.
It is also supplied in ampoules under the brand name Isuprel for injection and in sublingual pill form
for treatment of asthma, chronicbronchitis and emphysema.
Used with caution, it can also be used to treat torsades de pointes by acquired defect, in conjunction
with overdrive pacing andmagnesium sulfate.

Pharmacology[edit]
Isoprenaline is a 1 and 2 adrenoreceptor agonist which was commonly used to treat asthma before
the more widespread use of salbutamol, which has more selective effects on the airways. Its agonist
effects at TAAR1 provide it with a pharmacodynamic effects that resemble those of the
endogenous trace amines, like tyramine,[1] although its short half-life prevents it from producing
persistent psychoactive effects from TAAR1 activation in the central nervous system. Its route of
administration is either intravenous, oral, intranasal, subcutaneous, or intramuscular, depending on
use. The plasma half-life for isoprenaline is approximately two minutes.
Isoprenaline's effects on the cardiovascular system (non-selective) relate to its actions on cardiac
1 receptors and 2 receptors on smooth muscle within the tunica media of arterioles. Isoprenaline
has positive inotropic and chronotropic effects on the heart. 2adrenoceptor stimulation in arteriolar
smooth muscle induces vasodilation. Its inotropic and chronotropic effects elevate systolic blood
pressure, while its vasodilatory effects tend to lower diastolic blood pressure. The overall effect is to
decrease mean arterial pressuredue to the 2 receptors' vasodilation.
The adverse effects of isoprenaline are also related to the drug's cardiovascular effects. Isoprenaline
can produce tachycardia (an elevated heart rate), which predisposes patients to cardiac arrhythmias.

RS)-4-[1-hydroxy-2-(isopropylamino)ethyl]benzene-1,2-diol
DOBUTAMINE

Dobutamine
From Wikipedia, the free encyclopedia

Dobutamine

Systematic (IUPAC) name

RS)-4-(2-{[4-(4-hydroxyphenyl)butan-2yl]amino}ethyl)benzene-1,2-diol

Clinical data
Trade names

Dobutrex

AHFS/Drugs.com

monograph

MedlinePlus

a682861

Pregnancy
B

category
Routes of

Intravenous

administration
Legal status
Legal status
(Prescription only)
Pharmacokinetic data
Biological half-life

2 minutes

Identifiers
CAS Number

34368-04-2

ATC code

C01CA07 (WHO)

PubChem

CID 36811

IUPHAR/BPS

535

DrugBank

DB00841

ChemSpider

33786

UNII

0WR771DJXV

KEGG

D03879

ChEBI

CHEBI:4670

ChEMBL

CHEMBL926

Synonyms

Dobutrex, Inotrex
Chemical data

Formula

C18H23NO3

Molar mass

301.38 g/mol

Chirality

Racemic mixture

SMILES[show]

InChI[show]

(verify)

Dobutamine is a sympathomimetic drug used in the treatment of heart failure and cardiogenic
shock. Its primary mechanism is direct stimulation of 1 receptors of the sympathetic nervous
system. Dobutamine was developed in the 1970s by Drs. Ronald Tuttle and Jack Mills at Eli Lilly and
Company, as a structural analogue of isoprenaline.[1]
Contents
[hide]

1Clinical uses

2Adverse effects

3Pharmacology

4References

Clinical uses[edit]
Dobutamine is used to treat acute but potentially reversible heart failure, such as which occurs
during cardiac surgery or in cases ofseptic or cardiogenic shock, on the basis of its
positive inotropic action.[2]
Dobutamine can be used in cases of congestive heart failure to increase cardiac output. It is
indicated when parenteral therapy is necessary for inotropic support in the short-term treatment of
patients with cardiac decompensation due to depressed contractility, which could be the result of
either organic heart disease or cardiac surgical procedures. It is not useful in ischemic heart
diseasebecause it increases heart rate and thus increases myocardial oxygen demand.
The drug is also commonly used in the hospital setting as a pharmacologic stress testing agent to
identify coronary artery disease.

Adverse effects[edit]
Primary side effects include those commonly seen for 1 active sympathomimetics, such
as hypertension, angina, arrhythmia, andtachycardia. Used with caution in atrial fibrillation as it has
the effect of increasing the atrioventricular (AV) conduction. [3]
The most dangerous side effect of dobutamine is increased risk of arrhythmia, including fatal
arrhythmias.

Pharmacology[edit]
Dobutamine is a direct-acting agent whose primary activity results from stimulation of the 1adrenoceptors of the heart, increasing contractility and cardiac output. Since it does not act
on dopamine receptors to induce the release of norepinephrine (another 1agonist), dobutamine is
less prone to induce hypertension than is dopamine.
Dobutamine is predominantly a 1-adrenergic agonist, with weak 2 activity, and 1 selective activity,
although it is used clinically in cases of cardiogenic shock for its 1 inotropic effect in increasing heart
contractility and cardiac output. Dobutamine is administered as a racemic mixture consisting of both
(+) and () isomers; the (+) isomer is a potent 1 agonist and 1 antagonist, while the () isomer is an
1 agonist.[4] The administration of the racemate results in the overall 1 agonism responsible for its
activity. (+)-Dobutamine also has mild 2 agonist activity, which makes it useful as a vasodilator.[5]

Propranolol is a medication of the beta blocker type.[1] It is used to treat high blood pressure, a
number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anxiety,
and essential tremors.[1][2][3] It is used to prevent migraine headaches, and to prevent further heart
problems in those with angina or previous heart attacks.[1] It can be taken by mouth or byinjection into
a vein. The formulation that is taken by mouth comes in short acting and long acting versions.
Propranolol appears in the blood after 30 minutes and has a maximum (peak) effect between 60 and
90 minutes when taken by mouth.[1][4]
Common side effects include nausea, abdominal pain, and constipation. It should not be used in
those with an already slow heart rateand most of those with heart failure. Quickly stopping the
medication in those with coronary artery disease may worsen symptoms. It may worsen the
symptoms of asthma. Greater care is recommended in those with liver or kidney problems.
[1]

Propranolol may possibly cause harmful effects in the baby if taken during pregnancy.[5] Its use

during breastfeeding is likely okay but the baby should be monitored for side effects.[6] It is a nonselective beta blocker which works by blocking -adrenergic receptors.[1]
Propranolol was discovered in 1964.[7][8] It is on the World Health Organization's List of Essential
Medicines, the most important medications needed in a basic health system.[9] Propranolol is
available as a generic medication.[1] The wholes

RS)-1-(1-methylethylamino)-3-(1-naphthyloxy)propan-2-ol

Propranolol is used for treating various conditions, including:

Cardiovascular[edit]

Hypertension

Angina pectoris (with the exception of variant angina)

Tachyarrhythmia

Myocardial infarction

Tachycardia (and other sympathetic nervous system symptoms, such as muscle tremor)
associated with various conditions, including anxiety, panic, hyperthyroidism, and lithium therapy

Portal hypertension, to lower portal vein pressure

Prevention of esophageal variceal bleeding and ascites

While once a first-line treatment for hypertension, the role for beta blockers was downgraded in June
2006 in the United Kingdom to fourth-line, as they do not perform as well as other drugs, particularly
in the elderly, and evidence is increasing that the most frequently used beta blockers at usual doses
carry an unacceptable risk of provoking type 2 diabetes.[11]
Propranolol is not recommended for the treatment of hypertension by the Eighth Joint National
Committee (JNC 8) because a higher rate of the primary composite outcome of cardiovascular
death, myocardial infarction, or stroke compared to an angiotensin receptor blocker was noted in
one study.[12]

Psychiatric[edit]
It is occasionally used to treat performance anxiety.[2] Evidence to support the use in other anxiety
disorders is poor.[13] Some experimentation has been conducted in other psychiatric areas:[14]

Post-traumatic stress disorder (PTSD) and specific phobias (see subsection below)

Improvement of social communication skills in people with autism spectrum disorder[15]

Aggressive behavior of patients with brain injuries[16]

Treating the excessive drinking of fluids in psychogenic polydipsia[17][18]

PTSD and phobias[edit]

Propranolol is being investigated as a potential treatment for PTSD.[19][20] Propranolol works to inhibit
the actions of norepinephrine, aneurotransmitter that enhances memory consolidation. Individuals
given propranolol immediately after trauma experienced fewer stress-related symptoms and lower
rates of PTSD than respective control groups who did not receive the drug. [21] Due to the fact that
memories and their emotional content are reconsolidated in the hours after they are recalled/reexperienced, propranolol can also diminish the emotional impact of already formed memories; for
this reason, it is also being studied in the treatment of specific phobias, such
asarachnophobia, dental fear, and social phobia.[22]
Ethical and legal questions have been raised surrounding the use of propranolol-based medications
for use as a "memory damper", including: altering memory-recalled evidence during an investigation,
modifying behavioral response to past (albeit traumatic) experiences, the regulation of these drugs,
and others.[23] However, Hall and Carter have argued that many such objections are "based on wildly
exaggerated and unrealistic scenarios that ignore the limited action of propranolol in affecting
memory, underplay the debilitating impact that PTSD has on those who suffer from it, and fail to
acknowledge the extent to which drugs like alcohol are already used for this purpose." [24]

Others[edit]

Essential tremor. Evidence for use for akathisia however is insufficient[25]

Migraine and cluster headache prevention[26][27] and in primary exertional headache[28]

Hyperhidrosis (excessive sweating)

Proliferating infantile hemangioma

Glaucoma

Thyrotoxicosis by deiodinase inhibition

PINDOLOL
Medical use[edit]

Pindolol is used for hypertension in the US, Canada, and Europe, and also for angina
pectoris outside the US.[2] When used alone for hypertension, pindolol can significantly lower blood
pressure and heart rate, but the evidence base for its use is weak, as the number of subjects in
published studies is small.[2]
In some countries pindolol is also used for arrhythmias and prophylaxis of acute stress reactions.
[medical citation needed]

Contraindications[edit]
See also: Propranolol
Similar to propranolol with an extra contraindication for hyperthyroidism. In patients with
thyrotoxicosis, possible deleterious effects from long-term use of pindolol have not been adequately
appraised. Beta-blockade may mask the clinical signs of continuing hyperthyroidism or
complications, and give a false impression of improvement. Therefore, abrupt withdrawal of pindolol
may be followed by an exacerbation of the symptoms of hyperthyroidism, including thyroid storm. [3]
Pindolol has modest beta-adrenergic agonist activity and is therefore used with caution in angina
pectoris.

Pharmacology[edit]
Pindolol is a nonselective beta blocker with partial beta-adrenergic receptor agonist activity and also
possesses intrinsic sympathomimetic activity. This means that pindolol, particularly in high doses,
exerts effects like epinephrine or isoprenaline(increased pulse rate, increased blood pressure,
bronchodilation), but these effects are limited. Pindolol also shows membrane stabilizing
effects like quinidine, possibly accounting for its antiarrhythmic effects. It also functions as a 5HT1A receptor weak partial agonist / antagonist (Ki=33nM[4]).

Pharmacokinetics[edit]
Pindolol is rapidly and well absorbed from the GI tract. It undergoes some first-pass-metabolization
leading to an oral bioavailability of 50 to 95%. Patients with uremia may have a reduced
bioavailability. Food does not alter the bioavailability, but may increase the resorption. Following an
oral single dose of 20 mg peak plasma concentrations are reached within 1 to 2 hours. The effect of
pindolol on pulse rate (lowering) is evident after 3 hours. Despite the rather short halflife of 3 to 4
hours, hemodynamic effects persist for 24 hours after administration. Plasma halflives are increased
to 3 - 11.5 hours in patients with renal impairment, to 7 15 hours in elderly patients, and from 2.5 to

30 hours in patients with liver cirrhosis. Approximately 2/3 of pindolol are metabolized in the liver
giving hydroxylates, which are found in the urine as gluconurides and ethereal sulfates. The
remaining 1/3 of pindolol is excreted in urine in unchanged form.

RS)-1-(1H-indol-4-yloxy)-3-(isopropylamino)propan-2-ol

Atenolol is a selective 1 receptor antagonist, a drug belonging to the group of beta

blockers (sometimes written -blockers), a class of drugs used primarily in cardiovascular diseases.
Introduced in 1976, atenolol was developed as a replacement for propranolol in the treatment
of hypertension. It works by slowing down the heart and reducing its workload. Unlike propranolol,
atenolol does not readily pass through the bloodbrain barrier, thus decreasing the incidence
of central nervous system side effects.[1]
Atenolol is one of the most widely used -blockers in the United Kingdom and was once the first-line
treatment for hypertension.[citation needed] However, recent studies indicate that atenolol may not
reduce morbidity or mortality when used to treat hypertension, and may even increase mortality in
some subgroups.[2] In addition, the role for -blockers in general in hypertension was downgraded in
June 2006 in the United Kingdom, and later in the United States, as they are less appropriate than
newer drugs, particularly in the elderly.[citation needed]
Contents
[hide]

1Medical uses

2Side effects
o

2.1Overdose

3References

4External links

Medical uses[edit]

Atenolol is used for a number of conditions including: hypertension, angina, long QT

syndrome, acute myocardial infarction,supraventricular tachycardia, ventricular tachycardia, and the
symptoms of alcohol withdrawal.[3]
Off-label uses of Atenolol, as with other cardioselective -blockers, include symptomatic treatment of
psychological issues such as anxiety. -blockers are effective for some in treating the somatic
(physical) effects of anxiety. In these instances, dosing is used as needed instead of regular daily
dosing.
Due to its hydrophilic (water-attracting) properties, the drug is less suitable in migraine prophylaxis
compared to propranolol, because, for this indication, atenolol would have to reach the brain in high
concentrations, which is not the case, because atenolol does not pass through the bloodbrain
barrier.[1]

Side effects[edit]
See also: Beta blocker
Atenolol was the main -blocker identified as carrying a higher risk of provoking type 2 diabetes,
leading to its downgrading in the United Kingdom in June 2006 to fourth-line agent in the
management of hypertension.[4]
Antihypertensive therapy with atenolol provides weaker protective action against cardiovascular
complications (e.g. myocardial infarction and stroke) compared to other antihypertensive drugs. In
some cases, diuretics are superior.[5] In addition, atenolol has been found to lack mortality benefits [6]
[7]

and even to increase mortality in older adults.[2]

Overdose[edit]
Symptoms of overdose are due to excessive pharmacodynamic actions on 1 and also 2-receptors.
These include bradycardia (slow heartbeat), severe hypotension with shock, acute heart
failure, hypoglycemia and bronchospastic reactions. Treatment is largely symptomatic.
Hospitalization and intensive monitoring is indicated. Activated charcoal is useful to absorb the
drug. Atropine will counteract bradycardia, glucagon helps with hypoglycemia, dobutamine can be
given against hypotension and the inhalation of a 2-mimetic as hexoprenalin or salbutamol will
terminate bronchospasms. Blood or plasma atenolol concentrations may be measured to confirm a
diagnosis of poisoning in hospitalized patients or to assist in a medicolegal death investigation.
Plasma levels are usually less than 3 mg/L during therapeutic administration, but can range from 3
30 mg/L in overdose victims.[8][9]

RS)-2-{4-[2-Hydroxy-3-(propan-2-ylamino)propoxy]phenyl}acetamide

Acebutolol (trade names Sectral, Prent) is a beta blocker for the treatment
of hypertension and arrhythmias.
Contents
[hide]

1Pharmacology

2Pharmacokinetics

3Indications

4Contraindications

5Contraindications and Precautions

6Side effects

7External links

Pharmacology[edit]
Acebutolol is a cardioselective beta blocker with ISA (intrinsic sympathomimetic activity; see article
on pindolol). It is therefore more suitable than non cardioselective beta blockers, if a patient
with asthma or chronic obstructive pulmonary disease (COPD) needs treatment with a beta blocker.
(For these reasons, it may be a beta-blocker of choice in inclusion in Polypill strategies). In doses
lower than 800mg daily its constricting effects on the bronchial system and smooth muscle vessels
are only 10% to 30% of those observed under propranolol treatment, but there is experimental
evidence that the cardioselective properties diminish at doses of 800mg/day or more.
The drug has lipophilic properties, and therefore crosses the bloodbrain barrier. Acebutolol has no
negative impact on serum lipids (cholesterol and triglycerides). No HDL decrease has been
observed. In this regard, it is unlike many other beta blockers which have this unfavourable property.
The drug works in hypertensive patients with high, normal, or low renin plasma concentrations,
although acebutolol may be more efficient in patients with high or normal renin plasma
concentrations. In clinically relevant concentrations, a membrane-stabilizing effect does not appear
to play an important role.

Pharmacokinetics[edit]
Acebutolol is well absorbed from the GI tract, but undergoes substantial first-pass-metabolization,
leading to a bioavailability of only 35% to 50%. Peak plasma levels of acebutolol are reached within
2 to 2.5 hours after oral dosing. Peak levels of the main active metabolite, diacetolol, are reached
after 4 hours. Acebutolol has a half-life of 3 to 4 hours, and diacetolol a half-life of 8 to 13 hours.
Acebutolol undergoes extensive hepatic metabolization resulting in the desbutyl amine acetolol
which is readily converted into diacetolol. Diacetolol is as active as acebutolol (equipotency) and
appears to have the same pharmacologic profile. Geriatric patients tend to have higher peak plasma
levels of both acebutolol and diacetolol and a slightly prolonged excretion. Excretion is substantially
prolonged in patients with renal impairment, and so a dose reduction may be needed. Liver cirrhosis
does not seem to alter the pharmacokinetic profile of the parent drug and metabolite.

RS)-N-{3-acetyl-4-[2-hydroxy-3-(propan-2ylamino)propoxy]phenyl}butanamide

Labetalol, sold under the trade names Normodyne among others, is a mixed alpha/beta adrenergic
antagonist that is used to treat high blood pressure.[1] It can be given intravenously in severe
hypertensive situations, or by mouth for long term hypertension management. [2] Its dose and use is
limited by its main side effectpostural hypotension, where there is a substantial drop in blood
pressure when standing up.[3][4]
Labetalol's dual alpha- and beta- blockade has different physiological effects in short and long term
situations. In short term, acute situations, labetalol decreases blood pressure by
decreasing systemic vascular resistance with little effect on stroke volume, heart rate and cardiac
output.[5] During long term use, labetalol can reduce heart rate during exercise while
maintaining cardiac output by an increase in stroke volume.[6]

RS)-2-hydroxy-5-{1-hydroxy-2-[(4-phenylbutan-2yl)amino]ethyl}benzamide

ATROPINA
Atropine is a medication used to treat certain types of nerve agent and pesticide poisonings, some
types of slow heart rate, and to decrease saliva production during surgery.[3] It is typically
given intravenously or by injection into a muscle.[3] Eye drops are also available which are used to
treat uveitis and early amblyopia.[4] The intravenous solution usually begins working within a minute
and lasts half an hour to an hour.[1] Large doses may be required to treat poisonings.[3]
Common side effects include a dry mouth, large pupils, urinary retention, constipation, and a fast
heart rate. It should generally not be used in people with glaucoma.[3] While there is no evidence that
its use during pregnancy causes birth defects, it has not been well studied. It is likely safe during
breastfeeding.[5] It is an antimuscarinic (also known as an anticholinergic) that works by inhibiting
theparasympathetic nervous system.[3]
Atropine occurs naturally in a number of plants of the nightshade family including deadly
nightshade, Jimson weed, and mandrake.[6]It was first isolated in 1833.[7] Atropine is on the WHO
Model List of Essential Medicines, the most important medications needed in a basic health system.
[8]

It is available as a generic medication and not very expensive.[3][9] A one-milligram vial costs

wholesale between 0.06 and 0.44 USD.[10]

(RS)-(8-Methyl-8-azabicyclo[3.2.1]oct-3-yl) 3-hydroxy-2-phenylpropanoate

Medical uses[edit]

An ampoule containing atropine injection 1mL/0.5mg.

Eyes[edit]
Topical atropine is used as a cycloplegic, to temporarily paralyze the accommodation reflex, and as
a mydriatic, to dilate the pupils. Atropine degrades slowly, typically wearing off in 7 to 14 days, so it is
generally used as a therapeutic mydriatic, whereas tropicamide(a shorteracting cholinergic antagonist) or phenylephrine (an -adrenergic agonist) is preferred as an aid
to ophthalmic examination.
In refractive and accommodative amblyopia, when occlusion is not appropriate sometimes atropine
is given to induce blur in the good eye.[11] Evidence suggests that atropine penalization is just as
effective as occlusion in improving visual acuity.[12]
Atropine eye drops have been shown to be effective in slowing the progression of myopia in children
in several studies, but it is not available for this use, and side effects would limit its use. [13]

Heart[edit]
Injections of atropine are used in the treatment of bradycardia (a heart rate < 60 beats per minute).
Atropine was previously included in international resuscitation guidelines for use in cardiac arrest
associated with asystole and PEA, but was removed from these guidelines in 2010 due to a lack of

evidence for its effectiveness.[14] For symptomatic bradycardia, the usual dosage is 0.5 to 1 mg IV
push, may repeat every 3 to 5 minutes up to a total dose of 3 mg (maximum 0.04 mg/kg).[15]
Atropine is also useful in treating second-degree heart block Mobitz Type 1 (Wenckebach block),
and also third-degree heart blockwith a high Purkinje or AV-nodal escape rhythm. It is usually not
effective in second-degree heart block Mobitz type 2, and in third-degree heart block with a low
Purkinje or ventricular escape rhythm.
Atropine has also been used in an effort to prevent a low heart rate during intubation of children;
however, evidence does not support this use.[16]

Secretions[edit]
Atropine's actions on the parasympathetic nervous system inhibit salivary and mucus glands. The
drug may also inhibit sweating via the sympathetic nervous system. This can be useful in
treating hyperhidrosis, and can prevent the death rattle of dying patients. Even though atropine has
not been officially indicated for either of these purposes by the FDA, it has been used by physicians
for these purposes.[17]

Poisonings[edit]
Atropine is not an actual antidote for organophosphate poisoning. However, by blocking the action
of acetylcholine at muscarinic receptors, atropine also serves as a treatment for poisoning
by organophosphate insecticides and nerve gases, such as tabun (GA), sarin (GB),soman (GD)
and VX. Troops who are likely to be attacked with chemical weapons often carry autoinjectors with
atropine and obidoxime, for rapid injection into the muscles of the thigh. In a developed case of
nerve-gas poisoning, maximum atropinization is desirable. Atropine is often used in conjunction
with pralidoxime chloride.
Atropine is given as a treatment for SLUDGE
syndrome (salivation, lacrimation, urination, diaphoresis, gastrointestinal motility, emesis) symptoms
caused by organophosphate poisoning. Another mnemonic is DUMBBELSS, which stands for
diarrhea, urination, miosis, bradycardia, bronchoconstriction, excitation (as of muscle in the form of
fasciculations and CNS), lacrimation, salivation, and sweating (only sympathetic innervation using
muscarinic receptors).
Some of the nerve agents attack and destroy acetylcholinesterase by phosphorylation, so the action
of acetylcholine becomes excessive and prolonged. Pralidoxime (2-PAM) is the cure for
organophosphate poisoning because it can re-cleave this phosphorylation. Atropine can be used to

reduce the effect of the poisoning by blocking muscarinic acetylcholine receptors, which would
otherwise be overstimulated, by excessive acetylcholine accumulation.

Side-effects[edit]
Adverse reactions to atropine include ventricular fibrillation, supraventricular or
ventricular tachycardia, dizziness, nausea, blurred vision, loss of balance, dilated
pupils,photophobia, dry mouth and potentially extreme confusion,
dissociative hallucinations and excitation especially amongst the elderly. Most of available ampules
are carried on sulphate which can cause histamine release and anaphylaxis to susceptible patients
or patients with allergy to sulpha products.These latter effects are because atropine is able to cross
the bloodbrain barrier. Because of the hallucinogenic properties, some have used the
drug recreationally, though this is potentially dangerous and often unpleasant [medical citation needed].
In overdoses, atropine is poisonous. Atropine is sometimes added to potentially addictive drugs,
particularly anti-diarrhea opioid drugs such as diphenoxylate or difenoxin, wherein the secretionreducing effects of the atropine can also aid the anti-diarrhea effects.
Although atropine treats bradycardia (slow heart rate) in emergency settings, it can cause
paradoxical heart rate slowing when given at very low doses (i.e. <0.5 mg),[18]presumably as a result
of central action in the CNS.[19] One proposed mechanism for atropine's paradoxical bradycardia
effect at low doses involves blockade of inhibitory presynaptic muscarinic autoreceptors, thereby
blocking a system that inhibits the parasympathetic response.[20]
Atropine is incapacitating at doses of 10 to 20 mg per person. Its LD50 is estimated to be 453 mg per
person (by mouth) with a probit slope of 1.8.[21] The antidote to atropine
isphysostigmine or pilocarpine.
A common mnemonic used to describe the physiologic manifestations of atropine overdose is: "hot
as a hare, blind as a bat, dry as a bone, red as a beet, and mad as a hatter". [22]These associations
reflect the specific changes of warm, dry skin from decreased sweating, blurry vision, decreased
sweating/lacrimation, vasodilation, and central nervous system effects on muscarinic receptors, type
4 and 5. This set of symptoms is known as anticholinergic toxidrome, and may also be caused by
other drugs with anticholinergic effects, such
as scopolamine, diphenhydramine, phenothiazine antipsychotics and benztropine.[23]

Contraindications[edit]
Atropine is contraindicated in patients pre-disposed to narrow angle glaucoma.[medical citation needed]

Mechanism of action[edit]
In general, atropine counters the "rest and digest" activity of glands regulated by
the parasympathetic nervous system. This occurs because atropine is a competitive, reversible
antagonist of the muscarinic acetylcholine receptors (acetylcholine being the
main neurotransmitter used by the parasympathetic nervous system).
Atropine is a competitive inverse agonist for the muscarinic acetylcholine receptor types M1, M2,
M3, M4 and M5.[24] It is classified as an anticholinergic drug (parasympatholytic).
In cardiac uses, it works as a nonselective muscarinic acetylcholinergic antagonist, increasing firing
of the sinoatrial node (SA) and conduction through the atrioventricular node(AV) of the heart,
opposes the actions of the vagus nerve, blocks acetylcholine receptor sites, and
decreases bronchial secretions.[medical citation needed]
In the eye, atropine induces mydriasis by blocking contraction of the circular pupillary
sphincter muscle, which is normally stimulated by acetylcholine release, thereby allowing the
radial pupillary dilator muscle to contract and dilate the pupil. Atropine induces cycloplegia by
paralyzing the ciliary muscles, whose action inhibits accommodation to allow accurate refraction in
children, helps to relieve pain associated with iridocyclitis, and treats ciliary block
(malignant) glaucoma.[medical citation needed]

Chemistry and pharmacology[edit]

Atropine is a diastereomeric mixture of d-hyoscyamine and l-hyoscyamine, with most of its
physiological effects due to l-hyoscyamine. Its pharmacological effects are due to binding to
muscarinic acetylcholine receptors. It is an antimuscarinic agent. Significant levels are achieved in
the CNS within 30 minutes to 1 hour and disappears rapidly from the blood with a half-life of 2 hours.
About 60% is excreted unchanged in the urine, most of the rest appears in urine as hydrolysis and
conjugation products. Effects on the iris and ciliary muscle may persist for longer than 72 hours.
The most common atropine compound used in medicine is atropine sulfate (monohydrate)
(C17H23NO3)2H2SO4H2O, the full chemical name is 1 H, 5 H-Tropan-3- ol ()-tropate(ester), sulfate
monohydrate.
The vagus (parasympathetic) nerves that innervate the heart release acetylcholine (ACh) as their
primary neurotransmitter. ACh binds to muscarinic receptors (M2) that are found principally on cells
comprising the sinoatrial (SA) and atrioventricular (AV) nodes. Muscarinic receptors are coupled to

the Gi-protein; therefore, vagal activation decreases cAMP. Gi-protein activation also leads to the
activation of KACh channels that increase potassium efflux and hyperpolarizes the cells.
Increases in vagal activities to the SA node decreases the firing rate of the pacemaker cells by
decreasing the slope of the pacemaker potential (phase 4 of the action potential); this decreases
heart rate (negative chronotropy). The change in phase 4 slope results from alterations in potassium
and calcium currents, as well as the slow-inward sodium current that is thought to be responsible for
the pacemaker current (If). By hyperpolarizing the cells, vagal activation increases the cell's
threshold for firing, which contributes to the reduction in the firing rate. Similar electrophysiological
effects also occur at the AV node; however, in this tissue, these changes are manifested as a
reduction in impulse conduction velocity through the AV node (negative dromotropy). In the resting
state, there is a large degree of vagal tone on the heart, which is responsible for low resting heart
rates.
There is also some vagal innervation of the atrial muscle, and to a much lesser extent, the
ventricular muscle. Vagus activation, therefore, results in modest reductions in atrial contractility
(inotropy) and even smaller decreases in ventricular contractility.
Muscarinic receptor antagonists bind to muscarinic receptors thereby preventing ACh from binding to
and activating the receptor. By blocking the actions of ACh, muscarinic receptor antagonists very
effectively block the effects of vagal nerve activity on the heart. By doing so, they increase heart rate
and conduction velocity.

Homatropine (Equipin, Isopto Homatropine) is an anticholinergic medication that is an antagonist

at muscarinic acetylcholine receptors and thus the parasympathetic nervous system. It is used
in eye drops as a cycloplegic (to temporarily paralyzeaccommodation), and as a mydriatic (to dilate
the pupil). For Homatropine methylbromide see Methylhomatropine, this is a different medication.
Homatropine is less potent than atropine and has a shorter duration of action. It is available as
the hydrobromidesalt.
Homatropine is also given as an atropine substitute given to reverse the muscarinic and CNS effects
associated with indirectcholinomimetic (anti-AChase) administration.

Side effects[edit]

Blurred vision

Sensitivity to light

Contraindications[edit]

Untreated glaucoma

Myasthenia gravis

Severe heart failure

Thyrotoxicosis

N-Methyl-8-azabicyclo[3.2.1]oct-3-yl) 2-hydroxy-2-phenylacetate

Tropicamide (Mydriacyl) is an anticholinergic used as a mydriatic.[1]

Contents
[hide]

1Uses

2Side effects

3Illicit use

4References

Uses[edit]
Tropicamide is an antimuscarinic drug that produces short acting mydriasis (dilation of the pupil)
and cycloplegia[2] when applied aseye drops. It is used to allow better examination of
the lens, vitreous humor, and retina. Due to its relatively short duration of effect (48 hours), it is
typically used during eye examinations such as the dilated fundus examination, but it may also be
used before or aftereye surgery. Cycloplegic drops are often also used to treat anterior uveitis,
decreasing risk of posterior synechiae and decreasing inflammation in the anterior chamber of the
eye.
Tropicamide is occasionally administered in combination with p-hydroxyamphetamine (brand
name Paremyd), which is a sympathomimetic. The use of the sympathomimetic drug causes the iris
dilator muscle to be directly stimulated, causing increased dilation. In the United States, the

sympathomimetic drop most commonly used along with tropicamide, is

2.5% phenylephrinehydrochloride (brand name AK-Dilate).

Side effects[edit]
Tropicamide induces transient stinging and a slight and transient rise in intraocular pressure in the
majority of patients. It may cause redness or conjunctivitis (inflammation) and also blurs near vision
for a short while after instillation (care must be taken, and the patient must only drive when vision
returns to normal). Tropicamide may, in very rare cases [1], cause an attack of acute angle-closure
glaucoma. This tends to be in patients with narrow anterior chamber angles, and closure risk must
be assessed by the practitioner prior to instillation.
Tropicamide is often preferred to atropine because atropine has a longer half-life, causing prolonged
dilation and blurry vision for up to a week. Atropine has less sting effect, but can be toxic or fatal if
ingested in large quantities by children or adults.
Systemic side effects are very rare.

RS)-N-ethyl-3-hydroxy-2-phenyl-N-(pyridin-4-ylmethyl)propanamide

Propantheline bromide (INN) is an antimuscarinic agent used for the treatment of excessive
sweating (hyperhidrosis), cramps or spasms of the stomach, intestines (gut) or bladder, and
involuntary urination (enuresis). It can also be used to control the symptoms of irritable bowel
syndrome and similar conditions. This agent can also be used for patients who experience intense
GI symptoms while tapering off of TCAs. [1]
Contents
[hide]

1Indications

2Adverse effects

3Mechanism of action

4References

Indications[edit]
By relaxing the gut muscle, propantheline can relieve pain in conditions caused by spasm of the
muscle in the gut. Relaxing the smooth muscle in the bladder prevents the involuntary spasms that
can allow leakage of urine from the bladder in the condition known as enuresis (involuntary urination
in adults). Propantheline can also be used to treat excessive sweating because acetylcholine block
also reduces secretions such as sweat and tears.

Adverse effects[edit]
Side effects include tachycardia, constipation, hypersensitivity to light, dry mouth, and urinary
retention. This can also be prescribed by dentists for certain patients who salivate excessively. By
giving this medication it becomes easier to do "dry" dentistry

Mechanism of action[edit]
Propantheline is one of a group of antispasmodic medications which work by blocking the action of
the chemical messengeracetylcholine, which is produced by nerve cells, to muscarinic
receptors present in various smooth muscular tissues, in places such as the gut, bladder and eye.
Normally, the binding of acetylcholine induces involuntary smooth muscular contractions.

N-isopropyl-N-methyl-N-{2-[(9H-xanthen-9-ylcarbonyl)oxy]ethyl}propan-2aminium bromide

Pirenzepine (Gastrozepin), an M1 selective antagonist, is used in the treatment of peptic ulcers, as

it reduces gastric acid secretion and reduces muscle spasm. It is in a class of drugs known
as muscarinic receptor antagonists - acetylcholine being the neurotransmitter of the parasympathetic
nervous system which initiates the rest-and-digest state (as opposed to fight-or-flight), resulting in an
increase in gastric motility and digestion; whereas pirenzepine would inhibit these actions and cause

decreased gastric motility leading to delayed gastric emptying and constipation. [1] It has no effects on
the brain and spinal cord as it cannot diffuse through the bloodbrain barrier.
Pirenzepine has been investigated for use in myopia control.[2][3]
It promotes the homodimerization or oligomerisation of M1 receptors.[4]

11-[(4-methylpiperazin-1-yl)acetyl]-5,11-dihydro-6H-pyrido[2,3-b]
[1,4]benzodiazepin-6-one

Telenzepine is a thienobenzodiazepine acting as selective M1 antimuscarinic. It is used in the

treatment of peptic ulcers.[1]Telenzepine is atropisomeric, in other words the molecule has a
stereogenic CN-axis; in neutral aqueous solution it displays a half-life for racemization of the order
of 1000 years. The enantiomers have been resolved. The activity is related to the (+)-isomer which is
about 500-fold more active as the ()-isomer at muscarinic receptors in the rat cerebal cortex. [2]

1-methyl-10-[2-(4-methylpiperazin-1-yl)acetyl]-5H-thieno[3,4-b][1,5]benzodiazepin-4one

Mecamylamine (INN, BAN) (brand names Inversine, Vecamyl[1] ) or mecamylamine

hydrochloride (USAN) is a non-selective,non-competitive antagonist of the nicotinic acetylcholine
receptors (nAChRs) that was introduced in the 1950s as an antihypertensivedrug.[2] It was withdrawn
from the market for the treatment of hypertension in 2009 in the United States.[1]
Chemically, mecamylamine is a secondary aliphatic amine, with a pKaH of 11.2[3]

Pharmacology and clinical applications[edit]

Mecamylamine has been used as an orally-active ganglionic blocker in treating autonomic
dysreflexia and hypertension,[4] but, like most ganglionic blockers, it is more often used now as a
research tool.
Mecamylamine is also sometimes used as an antiaddictive drug to help people stop smoking
tobacco,[5] and is now more widely used for this application than it is for lowering blood pressure. This
effect is thought to be due to its blocking 34 nicotinic receptors in the brain. It has also been
reported to bring about sustained relief from tics in Tourette's Disorder when a series of more usually
used agents had failed [22].
In a recent double-blind, placebo-controlled Phase II trial in Indian patients with major depression,
(S)-mecamylamine (TC-5214) appeared to have efficacy as an augmentation therapy. This is the first
substantive evidence that shows that compounds where the primary pharmacology is antagonism to
neuronal nicotinic receptors will have antidepressant properties.[6][7] TC-5214 is currently in Phase III

of clinical development as an add-on treatment and on stage II as a monotherapy treatment for

major depression. The first results reported from the Phase III trials showed that TC-5214 failed to
meet the primary goal and the trial did not replicate the effects that had been encouraging in the
Phase II trial.[8][9] Development is funded by Targacept and AstraZeneca.[10] It did not produce
meaningful, beneficial results on patients as measured by changes on the Montgomery-Asberg
Depression Rating Scale after eight weeks of treatment as compared with placebo.
(S)-(+)-Mecamylamine dissociates more slowly from 42 and 34 receptors than does the (R)-()enantiomer.[11]
A large SAR study of mecamylamine and its analogs was reported by a group from Merck in 1962.
[12]

Another, more recent SAR study was undertaken by Suchocki et al.[13]

A comprehensive review of the pharmacology of mecamylamine was published in 2001. [14]

(1S,2R,4R)-N,2,3,3-Tetramethylbicyclo[2.2.1]heptan-2-amine

Trimetaphan camsilate (INN) or trimethaphan camsylate (USAN), trade name Arfonad, is a drug
that counteractscholinergic transmission at the ganglion type of nicotinic receptors of the autonomic
ganglia and therefore blocks both thesympathetic nervous system and the parasympathetic nervous
system. It acts as a non-depolarizing competitive antagonist at the nicotinic acetylcholine receptor, is
short-acting, and is given intravenously.

Effects[edit]
Trimetaphan is a sulfonium compound and therefore carries a positive charge. Being charged, it
cannot cross lipid cell membranes, such as those that comprise the bloodbrain barrier. Due to this,
trimethaphan does not have any effect on thecentral nervous system.
The ciliary muscle of the eye functions to round the lens for accommodation and is controlled mainly
by parasympathetic system input. With administration of a ganglion-blocking drug, the ciliary muscle
cannot contract (cycloplegia) and the patient loses the ability to focus their eyes.

Trimetaphan has a strong effect on the cardiovascular system. The size of blood vessels is primarily
controlled by the sympathetic nervous system. Loss of sympathetic system input to the blood
vessels causes them to get larger (vasodilation) which has the effect of lowering blood
pressure. Postural hypotension is a common side effect of such drugs. Trimethaphan causes a
histamine release which further lowers blood pressure. Effects on the heart include a decreased
force of contraction and an increase in heart rate (tachycardia). Reflexive tachycardia can be
diminished or undetected because trimetaphan is also blocking the sympathetic ganglia innervating
the heart.
The motility of the gastrointestinal tract is regulated by the parasympathetic system, and blockage of
this input results in diminished motility and constipation.

Therapeutic uses[edit]
The therapeutic uses of trimetaphan are very limited due to the competition from newer drugs that
are more selective in their actions and effects produced. It is occasionally used to treat
a hypertensive crisis and dissecting aortic aneurysm, to treatpulmonary edema, and to reduce
bleeding during neurosurgery

Generic Name: succinylcholine (SUX-i-nil-KOE-leen)

Brand Name: Examples include Anectine and Quelicin
Succinylcholine has been associated with rapid muscle breakdown resulting in life-threatening heart
rhythms, cardiac arrest, and death in children. These children appeared to be healthy, but were later
found to have certain undiagnosed muscle problems (eg, Duchenne muscular dystrophy). Male
children and children younger than 8 years old seem to be at a higher risk. Cases have also been
reported in adolescents. Because it is hard to determine which children may be at risk,
succinylcholine should only be used in an emergency situation.

Succinylcholine is used for:

Relaxing muscles during surgery or when using a breathing machine (ventilator). It is
also used to induce anesthesia or when a tube must be inserted in the windpipe. It may
also be used for other conditions as determined by your doctor.
Succinylcholine is a depolarizing muscle relaxant. It works by keeping muscles from
contracting, which causes paralysis of the muscles in the face and those used to
breathe and move.