All ANS Drugs

All ANS Drugs
ANS Neurotransmitters
Acetylcholine
Trade Name: Miochol-E

Drug Class: Cholinomimetic (direct acting muscarinic & nicotinic agonist)
Mechanism of Action:
o The endogenous agonist for muscarinic and nicotinic receptors.
o Acetylcholine is the primary neurotransmitter responsible for neurotransmission at:
1. All autonomic ganglia (sympathetic & parasympathetic)(nicotinic)
2. All post-ganglionic parasympathetic neurons (e.g. vagal innervation of
the heart)(muscarinic)
3. Post-ganglionic motor neurons (which innervate skeletal
muscle)(nicotinic)
4. Sympathetic postganglionic neurons that innervate sweat glands
(muscarinic)
5. Preganglionic sympathetic nerves that innervate the adrenal medulla
(nicotinic), resulting in the release of epinephrine and norepinephrine into the
systemic circulation.
o Muscarinic receptors mediate their responses by G-proteins
o Nicotinic receptors mediate their responses by opening a cationic ion channel that
is an intrinsic component of the nicotinic-receptor-channel complex
Indications:
o To produce miosis (reduction of size) of the iris in seconds after delivery to
the lens in cataract surgery, and in other types of eye surgery where rapid
miosis is required (e.g. in penetrating keratoplasty, iridectomy and other anterior
segment eye surgery). Direct application of acetylcholine to the iris will cause rapid
miosis of short duration (by acting as a muscarinic agonist). Topical ocular
instillation of acetylcholine to the intact eye causes no discernible response as
cholinesterase destroys the molecule more rapidly than it can penetrate the cornea.
Side Effects:
o Rare when applied only to the eye
o If given i.v. - acetylcholine will produce a dose-dependent reduction of
blood pressure & associated changes in heart rate.
Note: following administration of an i.v. bolus, acetylcholine will
stimulate muscarinic receptors located on the vascular endothelium,
resulting in the release of nitric oxide. Nitric oxide will relax arterial
smooth muscle, resulting in a fall in arterial blood pressure. The fall
in arterial pressure will in turn produce an associated baroreceptor
mediated increase in heart rate. If the baroreceptor reflex is blocked
by either a ganglionic blocker or a beta blocker, then acetylcholine's
direct effect on the SA node to reduce heart rate can typically be
observed.
Pharmacokinetics:
o After release from the nerve ending, acetylcholine is rapidly inactivated by the
enzyme acetylcholinesterase by hydrolysis to acetic acid and choline.
Notes:
Muscarine and nicotine are naturally occurring alkaloids that were used to
pharmacologically identify and characterize receptor subtypes before the
endogenous neurotransmitter (acetylcholine or Vagusstoff) was identified.
References:
o Pappano AJ (2012) Cholinoceptor-Activating & Cholinesterase-Inhibiting Drugs
(Chapter 7). In: Basic & Clinical Pharmacology. 12e. Katzung BG, Masters SB, Trevor
AJ (Editors). McGraw-Hill / Lange. (Access-Medicine)
o rxlist.com (Miochol )
o
Keywords
Norepinephrine
Trade Name: Levophed

Drug Class: Catecholamine, Sympathomimetic
o Functions as a peripheral vasoconstrictor (by stimulating 1 and 2 adrenergic
receptors) and as an inotropic stimulator of the heart (by stimulating 1
adrenergic receptors)
o When given i.v. norepinephrine increases both total peripheral resistance, as well as
systolic and diastolic blood pressure
Note: Compensatory vagal reflexes tend to overcome the direct positive
chronotropic effects on the heart (since both branches of the ANS innervate
the SA node), but do not eliminate the positive inotropic effects on the
ventricle (which does not have significant vagal innervation).
o Norepinephrine is an endogenous catecholamine synthesized in the adrenal medulla
that is the biochemical precursor of epinephrine
o Norepinephrine is the transmitter of most sympathetic postganglionic fibers of the
CNS
Indications:
o For blood pressure control in certain acute hypotensive states (e.g.,
pheochromocytomectomy, sympathectomy poliomyelitis, spinal anesthesia,
myocardial infarction septicemia, blood transfusion, and drug reactions)
o As an adjunct in the treatment of cardiac arrest and profound hypotension
Contraindications: (see also - Drug Interactions)
o Norepinephrine should not be given to patients who are hypotensive from blood
volume deficits except as an emergency measure to maintain coronary and cerebral
artery perfusion until blood volume replacement therapy can be completed.
Note: If it is used in hypovolemic patients, the following may occur: severe
peripheral and visceral vasoconstriction, decreased renal perfusion and urine
output, poor systemic blood flow despite normal blood pressure, tissue
hypoxia, and lactic acidosis.
Side Effects:
o When given as a bolus i.v. there is the potential for:
Ischemic injury due to potent vasoconstrictor action and tissue hypoxia
Mild bradycardia, probably as a reflex result of a rise in blood pressure
Arrhythmias
Anxiety
Transient headache
Respiratory difficulty
Pharmacokinetics:
When released from nerve terminals, its actions are primarily (75%)
terminated by neuronal reuptake
o Diffusion and degredation by extracellualr COMT contribute to a lesser extent. When
given as an i.v. bolus, redistribution (and associated fall in concentration) also
contributes to the decrease in effect as a function of time
Drug Interactions:
o Halogenated anesthetics (e.g. halothane) increase cardiac automatic irritability and
therefore seem to sensitize the myocardium to the action of intravenously
administered epinephrine or norepinephrine, resulting in an increased incidence of
cardiac arrhythmias
o Norepinephrine should be used with extreme caution in patients receiving
monoamine oxidase inhibitors (MAOI) or tricyclic antidepressants, because severe,
prolonged hypertension may result
Notes:
o Another synonym for noreinephrine is levarterenol. The British name for
norepinephrine is noradrenaline.
References:
o Biaggioni I, Robertson D (2012): Adrenoceptor Agonists & Sympathomimetic Drugs
o rxlist.com (Levophed )
o
Keywords
Epinephrine
Trade Name: generic, Adrenalin, Epipen

Drug Class: Catecholamine, Sympathomimetic
o Epinephrine stimulates both 1 & 2 and 1 & 2 receptor subtypes on
sympathetic effector cells.
o When given i.v. it is a very potent vasoconstrictor and cardiac stimulant.
The rise in systolic blood pressure results from a 1 mediated increase in
heart rate and ventricular contractility
The rise in diastolic pressure results from stimulation of 1 and 2 receptor
mediated vasoconstriction in many vascular beds
Epinephrine also stimulates 2 receptors present in skeletal muscle blood
vessels, resulting in their dilation
At low doses, at which 2 receptor stimulation predominates
over receptor stimulation, total peripheral resistance and
diastolic pressure may fall
Under physiological conditions, epinephrine released from the adrenal
gland functions as a hormone and, via activation of 2 receptors,
contributes to increased blood flow during exercise.
2 stimulation will cause bronchodilation in the lung and activate
glycogenolysis in the liver
Indications:
1. a drug of choice for treatment of acute anaphylactic reactions (hypersensitivity
reactions to drugs, animal serums and other allergens)
2. a secondary drug for treatment of acute asthmatic attacks to relieve
bronchospasm (selective beta-2 agonists such as albuterol are considered 1st line
drugs for this indication, since they have fewer side effects)
3. treatment and prophylaxis of cardiac arrest and attacks of transitory

atrioventricular (A-V) heart block with syncopal seizures (Stokes-Adams
Syndrome).
4. combined with many local anesthetics to reduce the systemic absorption of
anesthetic, and increase their duration of action.
Contraindications:
o Epinephrine should be used cautiously in patients with hyperthyroidism,
hypertension and cardiac arrhythmias
Side Effects:
o Transient and minor side effects of:
Anxiety
Tachycardia
Headache
Fear and palpitations occur with systemic therapeutic doses
Adverse effects such as cardiac arrhythmias and excessive rise in blood
pressure may also occur with therapeutic doses or inadvertent overdosage
Side effects are more likely to be observed in hyperthyroid individuals
Pharmacokinetics:
o Route of administration depends on the indication for its use. It can be given i.v.,
s.c., i.m., via an endotracheal tube, or direct injection into the left ventricle.
o Relatively short duration of action compared to beta-2 selective agonists.
o The popular inhalational OTC formulation (Primatene Mist ) containing
chlorofluorohydrocarbons was discontinued on Dec 31, 2011 due to legal restrictions
on the use of environmental pollutants known to damage the ozone layer. A more
environmentally friendly formulation is likely to be approved in the near future.
Drug Interactions:
o All vasopressors should be used cautiously in patients taking monoamine oxidase
(MAO) inhibitors.
Notes:
o The British name for epinephrine is adrenaline
References:
AJ (Editors).
o Boushey HA (2012): Drugs Used in Asthma (Chapter 20). In: Basic and Clinical
Pharmacology. 12e. B Katzung, SB Masters AJ Trevor (Editors); McGraw-Hill (Access
Medicine).
o rxlist.com - epinephrine (Adrenalin )
Keywords
Dopamine
Trade Names: generic, intropin

Drug Class: Sympathomimetic, Catecholamine
o Dopamine is the immediate metabolic precursor of norepinephrine.
o At LOW DOSES it selectively activates D1 receptors in several vascular beds
(e.g. kidney) resulting in vasodilation. The D1 mediated effect to increase renal
blood flow may be of clinical significance (e.g. in the treatment of shock).
Activation of presynaptic D2 receptors may suppress norepinephrine release.
o At INTERMEDIATE DOSES dopamine activates 1 receptors in the heart.
At HIGH DOSES dopamine activates receptors leading to

vasoconstriction, including the renal vascular bed. High doses of dopamine
may mimic the actions of epinephrine.
o Dopamine is also a neurotransmitter in certain areas of the central nervous system,
especially in the nigrostriatal tract, and in a few peripheral sympathetic nerves.
Indications:
o For the correction of hemodynamic imbalances present in shock due to
myocardial infarction, trauma, endotoxic septicemia, open-heart surgery,
renal failure, and chronic cardiac decompensation as in congestive failure
Contraindications:
o Dopamine should not be used in patients with pheochromocytoma or patients with
uncorrected tachyarrhythmias or ventricular fibrillation.
Side Effects:
o Cardiac arrhythmias
o Dyspnea
o Nausea
o Vomiting
o Headache
Pharmacokinetics:
o Dopamines onset of action occurs within five minutes of intravenous administration,
and with dopamines plasma half-life of about two minutes, the duration of action is
less than ten minutes. However, if monoamine oxidase (MAO) inhibitors are present,
the duration may increase to one hour.
Drug Interactions:
o Patients who have been treated with MAO inhibitors within two to three weeks prior
to the administration of dopamine HCl should receive initial doses of 1/10th normal
o Tricyclic antidepressants may potentiate the pressor response to adrenergic agents
o Cardiac effects of dopamine are antagonized by beta-adrenergic blocking agents
o Haloperidol and haloperidol-like drugs suppress the dopaminergic renal and
mesenteric vasodilation induced at low rates of dopamine infusion
References:
AJ (Editors).
o rxlist.com (Dopamine)
o
Keywords
Cholinomimetic Agents
Pilocarpine
Trade Names: generic, Salagen, Isopto Carpine

Drug Class: Muscarinic cholinomimetic (tertiary alkaloid), muscarinic agonist
o A cholinergic parasympathomimetic agent exerting a broad spectrum of
pharmacologic effects with predominant muscarinic action
Indications:
o Treatment of dry mouth (Salagen ) resulting from salivary gland hypofunction
caused by:
Radiotherapy for cancer of the head and neck
Sjgrens syndrome, an autoimmune disorder where immune cells attack and

destroy the glands that produce tears and saliva
o Treatment of glaucoma (Open-Angle & Acute Angle-Closure)(Isopto Carpine )
eye drops containing pilocarpine cause contraction of the ciliary muscle which
opens the trabecular meshwork spaces to increase the outflow of aqueous
humor through the canal of Schlemm, thereby lowering intra-ocular pressure.
pilocarpine drops also cause miosis by causing contraction of the iris sphincter
muscle. This can be beneficial as well in lowering intraocular pressure in
certain types of angle-closure glaucoma (rxlist.com)
Contraindications:
o Uncontrolled asthma
o Known hypersensitivity to pilocarpine
o When miosis is undesirable
Side Effects:
o The most frequent adverse experiences are a consequence of the expected
pharmacologic effects of pilocarpine & include sweating, flushing, increased
urinary frequency.
Pharmacokinetics:
o Well absorbed from most sites of administration
o Crosses the blood brain barrier (its a tertiary amine)
Drug Interactions:
o Administered with caution to patients taking beta blockers because of the possibility
of cardiac conduction disturbances
Notes:
o Pilocarpine is a natural alkaloid
References:
o rxlist.com - Isopto Carpine
o rxlist.com - Salagen
Keywords
Bethanechol
Trade Names: generic, Urecholine

Drug Class: Muscarinic Cholinomimetic
o It increases the tone of the detrusor urinae muscle, usually producing a contraction
sufficiently strong to initiate micturition and empty the bladder
o It stimulates gastric motility, increases gastric tone, and often restores impaired
rhythmic peristalsis
o Because of the selective action of bethanechol, nicotinic symptoms of
cholinergicstimulation are usually absent or minimal
Indications:
o Treatment of acute postoperative & postpartum nonobstructive urinary
retention
o Neurogenic atony of the urinary bladder with retention.
Contraindications:
o Hypersensitivity to bethanechol chloride tablets,
o Hyperthyroidism
Peptic ulcer
Latent or active bronchial asthma,
Pronounced bradycardia or hypotension
Vasomotor instability
Coronary artery disease
Epilepsy
Parkinsonism
Side Effects:
o Early signs of overdosage are abdominal discomfort, salivation, flushing of the skin
(hot feeling), sweating, nausea and vomiting (SLUDE-like symptoms).
o Atropine is a specific antidote
Pharmacokinetics:
o Bethanechol chloride does not cross the blood-brain barrier because of its charged
quaternary amine moiety.
o The metabolic fate and mode of excretion of the drug have not been elucidated.
o Administer orally or s.c.; do not give by i.v. injection due to the risk of hypotension
& bradycardia
Drug Interactions:
o Special care is required if this drug is given to patients receiving ganglion blocking
compounds because a critical fall in blood pressure may occur. Usually, severe
abdominal symptoms appear before there is such a fall in the blood pressure.
References:
o rxlist.com (Bethanechol)
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Keywords
Nicotine
Trade Names: Nicotrol Inhaler

Drug Class: Nicotinic Cholinomimetic
o Binds stereo-selectively to nicotinic-cholinergic receptors at the autonomic
ganglia, in the adrenal medulla, at neuromuscular junctions, and in the brain
o Two types of central nervous system effects are believed to be the basis of nicotines
positively reinforcing properties:
A stimulating effect is exerted mainly in the cortex via the locus
ceruleus
A reward effect is exerted in the limbic system
At low doses the stimulant effects predominate while at high doses the
reward effects predominate
o The cardiovascular effects of nicotine include peripheral vasoconstriction,
tachycardia, and elevated blood pressure
Indications:
o Aid to smoking cessation for the relief of nicotine withdrawal symptoms
Contraindications:
o Known hypersensitivity or allergy to nicotine or to menthol
Side Effects:
o Nausea
o Abdominal pain
Vomiting, diarrhea,
Diaphoresis (profuse sweating)
Flushing
Dizziness
Disturbed hearing and vision,
Confusion
Weakness
Palpitations
Altered respiration
Hypotension
Pharmacokinetics:
o Nicotine is well absorbed through the skin
Major drug Interactions:
o May alter the pharmacokinetics of certain concomitant medications, such as tricyclic
antidepressants and theophylline. Doses of these and perhaps other medications
may need to be adjusted in patients who successfully quit smoking.
Notes:
o Acute tolerance (a reduction in response for a given dose) develops rapidly (less
than 1 hour), but not at the same rate for different physiologic effects (skin
temperature, heart rate, subjective effects)
o Withdrawal symptoms such as cigarette craving can be reduced in most individuals
by plasma nicotine levels lower than those from smoking
o Withdrawal from nicotine in addicted individuals can be characterized by craving,
nervousness, restlessness, irritability, mood lability, anxiety, drowsiness, sleep
disturbances, impaired concentration, increased appetite, minor somatic complaints
(headache, myalgia, constipation, fatigue), and weight gain
References:
o Luscher C (2012) Drugs of Abuse (Chapter 32). In: Basic & Clinical Pharmacology.
12e. Katzung BG, Masters SB, Trevor AJ (Editors). McGraw-Hill / Lange. (AccessMedicine)
o rxlist.com (Nicotrol )
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Keywords
Carbamate Cholinesterase Inhibitors

Physostigmine
Trade Names: generic

Drug Class: Reversible Carbamate Anticholinesterase
o A reversible anticholinesterase which effectively increases the concentration of
acetylcholine at the sites of cholinergic transmission
Indications:
o To reverse the anticholinergic effects upon the CNS & peripheral nervous
system that are caused by numerous drugs & plants capable of producing
the anticholinergic syndrome (see Notes)
Contraindications:
Physostigmine should not be used in the presence of asthma, gangrene, diabetes,

cardiovascular disease, mechanical obstruction of the intestine or urogenital tract or
any vagotonic state, and in patients receiving choline esters and depolarizing
neuromuscular blocking agents (decamethonium, succinyicholine)
Side Effects:
o nausea, vomiting, and salivation
o Appropriate antidote is atropine sulfate
Pharmacokinetics:
o Physostigmine contains a tertiary amine and easily penetrates the blood brain
barrier, while an anticholinesterase, such as neostigmine, which has a quatenary
ammonium ion is not capable of crossing the barrier
Notes:
o Pralidoxime (2-PAM) & other oximes should not be used to counteract the toxicity
caused by carbamate type anticholinesterases. Oximes are effective against
organophosphate anticholinesterases only.
o SOME DRUGS WHICH PRODUCE THE ANTICHOLINERGIC SYNDROME: Amitriptyline,
Amoxapine, Anisotropine, Atropine, Benztropine, Biperiden, Carbinoxamine,
Clidinium, Cyclobenzaprine, Desipramine, Doxepin, Homatropine, Hyoscine,
Hyoscyamine, Hyoscyamus, Imipramine, Lorazepam, Maprotiline, Mepenzolate,
Nortriptyline, Propantheline, Protriptyline, Scopolamine, Trimipramine
o SOME PLANTS THAT PRODUCE THE ANTICHOLINERGIC SYNDROME: Black
Henbane, Deadly Night Shade, Devils Apple, Jimson Weed, Loco Seeds or Weeds,
Matrimony Vine, Night Blooming Jessamine, Stinkweed
References:
o rxlist.com (Physostigmine)
o
Keywords
Neostigmine
Trade Names: generic, Prostigmin

Drug Class: Carbamate Anticholinesterase, Cholinomimetic
o Inhibits the hydrolysis of acetylcholine by competing with acetylcholine for
attachment to acetylcholinesterase at sites of cholinergic transmission
o It enhances cholinergic action by facilitating the transmission of impulses across
neuromuscular junctions
o It also has a direct cholinomimetic effect on skeletal muscle and possibly on
autonomic ganglion cells
o Because it contains a quaternary ammonium group it does not cross the bloodbrain barrier
Indications:
o For symptomatic treatment of myasthenia gravis
o Its greatest usefulness is in prolonged therapy where no difficulty in swallowing is
present
o In acute myasthenic crisis where difficulty in breathing and swallowing is present,
the parenteral form (neostigmine methylsulfate) should be used. The patient can be
transferred to the oral form as soon as it can be tolerated.
Contraindications:
Patients with known hypersensitivity to the drug

Contraindicated in patients with peritonitis or mechanical obstruction of the intestinal
or urinary tract
Side Effects:
o Generally due to an exaggeration of pharmacological effects of which salivation and
fasiculation are the most common
o Bowel cramps and diarrhea may also occur
o For a more complete list, see the rxlist.com reference
Pharmacokinetics:
o Neostigmine bromide is poorly absorbed from the gastrointestinal tract following oral
administration
o As a rule, 15 mg of neostigmine bromide given orally is equivalent to 0.5 mg of
neostigmine methylsulfate given parenterally
o Certain aminoglycoside antibiotics, especially neomycin, streptomycin and
kanamycin, have a mild but definite nondepolarizing blocking action which may
accentuate neuromuscular block. These antibiotics should be used in the myasthenic
patient only where definitely indicated.
References:
o rxlist.com (Prostigmin )
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Keywords
Pyridostigmine
Trade Names: Mestinon, Regonol

Drug Class: carbamate cholinesterase inhibitor (reversible)
o Inhibits the destruction of acetylcholine by cholinesterase
Indications:
o Treatment of myasthenia gravis
o Prophylaxis against poisoning by Soman nerve gas (which otherwise produces
rapid irreversible aging)
Pyridostigmine is needed for adequate protection against soman. If personnel
take pyridostigmine in advance of exposure, soman will be prevented from
binding to AChE because the AChE binding sites are occupied by
pyridostigmine, and so aging cannot take place.
The armed forces estimate that during a chemical attack, many personnel
may be exposed to 5 times the lethal dose (LD) of soman, so a protective
ratio (that raises the LD) by at least 5 times is needed. Addition of
pyridostigmine allows the protective ratio to exceed 5 for soman (according to
studies in monkeys).
Clinical trials (pyridostigmine is clinically used in myasthenia gravis) indicate
that pyridostigmine is well-tolerated at the doses intended for military use.
Pyridostigmine should be started (oral tablets) at least several hours
before exposure to soman (8 hours in advance is preferred), and
discontinued upon exposure to the nerve gas, at which point atropine and
pralidoxime are given at the first indication of exposure.
Pyridostigmine pretreatment does not confer an advantage against

sarin, based on studies in animals; personnel have enough time to take
oxime after exposure to this nerve agent before aging takes place,
reactivating the AChE molecule. Indeed, soman is the only nerve agent for
which PB is known to be necessary to produce an adequate protective ratio.
Contraindications:
o Mechanical intestinal or urinary obstruction
o Particular caution should be used in its administration to patients with bronchial
asthma
Side Effects:
o SLUDE. With overdose it can produce muscarinic & nicotinic symptoms
Muscarinic: nausea, vomiting, diarrhea, abdominal cramps, increased
peristalsis, increased salivation, increased bronchial secretions, miosis and
diaphoresis
Nicotinic side effects are comprised chiefly of muscle cramps, fasiculation and
weakness
Overdosage may result in cholinergic crisis, a state characterized by
increasing muscle weakness which, through involvement of the muscles of
respiration, may lead to death
Pharmacokinetics:
o Oral administration. The size and frequency of the dosage should be adjusted to the
needs of the individual patient.
o Pyridostigmine is mainly excreted unchanged by the kidney
o Pyridostigmine is a quaternary amine (permanently charged) and does not readily
cross the blood brain barrier
Notes:
o Chemically related to neostigmine, but has a longer duration of action and
less GI effects
References:
o rxlist.com pyridostigmine (Mestinon )
o fda.gov (Prophylactic use against poisoning by Soman nerve gas)
Keywords
Quaternary Alcohol Cholinesterase

Inhibitors
Edrophonium
Trade Names: generic, Enlon Plus, Tensilon

Drug Class: Anticholinesterase (quaternary alcohol subtype)
o A short and rapid-acting anticholinesterase
o Positively charged quaternary alcohol that binds reversibly to the anionic site on
cholinesterase
Indications:
1. For the differential diagnosis of myasthenia gravis (the Tensilon Test) and
as an adjunct in the evaluation of treatment requirements in this disease. It may
also be used for evaluating emergency treatment in myasthenic crises. Because of
its rapid onset of action (30 sec) and brief duration of action (~5 minutes), it is not
recommended for maintenance therapy in myasthenia gravis (Drachman, 2012).
YouTube video of the Tensilon Test performed in a dog with Myasthenia
Gravis
2. Useful whenever an antagonist is needed to reverse the neuromuscular
block produced by curare, or curare-like NMJ blocker (e.g. tubocurarine,
gallamine triethiodide or dimethyl-tubocurarine)
It is not effective against depolarizing skeletal muscle relaxants
(succinylcholine)
3. It may be used adjunctively in the treatment of respiratory depression caused by
curare overdosage
Contraindications:
o Known hypersensitivity to anticholinesterase agents
o Intestinal and urinary obstructions of mechanical type
Side Effects:
o The myasthenic patient in crisis who is being tested with edrophonium should be
observed for bradycardia or cardiac standstill and cholinergic reactions if an
overdose is given.
o Muscarine-like symptoms (nausea, vomiting, diarrhea, sweating, increased bronchial
and salivary secretions and bradycardia) often appear with overdosage (cholinergic
crisis)
o An important complication that can arise is obstruction of the airway by bronchial
secretions
Pharmacokinetics:
o IV and IM administration
o Rapid renal excretion, resulting in a short duration of action
o Care should be given when administering this drug to patients with symptoms of
myasthenic weakness who are also on anticholinesterase drugs
o Since symptoms of anticholinesterase overdose (cholinergic crisis) may mimic
underdosage (myasthenic weakness), their condition may be worsened by the use of
this drug
References:
o Drachman DB (2012): Myasthenia Gravis and Other Diseases of the Neuromuscular
Junction (Chapter 386). In: Harrison's Internal Medicine. 18e. McGraw-Hill.
o rxlist.com (Enlon )
Keywords
Organophosphate Cholinesterase
Inhibitors
Echothiophate
Trade Name: Phospholine Iodide

Drug Class: Anticholinesterase (Organophosphate)
o Irreversible long-acting cholinesterase inhibitor for topical use to enhance the
effect of endogenously liberated acetylcholine in the iris, ciliary muscle, and other
parasympathetically innervated structures of the eye
o It causes miosis, increases the outflow of aqueous humor, causes a fall in intraocular
pressure, and potentiation of accommodation
Indications:
o Treatment of glaucoma (if beta-blockers fail)
o Because of it's long duration of action, it is useful for round the clock control of
intraocular pressure
o Also indicated for accommodative esotropia (a pediatric use)
Contraindications:
o Active uveal inflammation
o Most cases of angle-closure glaucoma, due to the possibility of increasing angle
block
o Hypersensitivity to the active or inactive ingredients
Side Effects:
o Retinal detachment has been reported in a few cases
o Stinging, burning, lacrimation
o Iris cysts may form
o Lens opacities
o Cardiac irregularities
Pharmacokinetics:
o Administered in eye drops to patients with glaucoma
o Forms an irreversible covalent bond with the ACh binding site on
cholinesterase (duration of action is ~100 hrs)
Drug Interactions:
o Potentiates other cholinesterase inhibitors such as succinylcholine or
organophosphate and carbamate insecticides
o Patients undergoing systemic anticholinesterase treatment should be warned of the
possible additive effects
References:
o rxlist.com (Phospholine )
Keywords
Sarin (GB)
Drug Class:
o Organophosphate anticholinesterase & a human-made chemical warfare
agent (nerve agent)
o Originally synthesized as a pesticide
o Sarin is the most volatile of the nerve agents, which means that it can easily and
quickly evaporate from a liquid into a vapor and spread into the environment
o People can be exposed to the vapor even if they do not come in contact with the
liquid form of sarin
Once sarin binds to cholinesterase the chemical stability of it's interaction with
the enzyme can become irreversible with time due to the loss of an alkyl
group. When this happens it's binding becomes irreversible (aging) and the
complex becomes resistant to the effects of oxime regenerators such as pralidoxime
o Aging develops within 3-5 hours with sarin.
Indications:
o Terrorism / Chemical Warfare, Weapon of Mass Destruction
Effects:
o Remember SLUDE muscarinic & nicotinic symptoms
o Symptoms will appear within a few seconds after exposure to the vapor form of
sarin and within a few minutes to up to 18 hours after exposure to the liquid form
(see below)
o A long term study of soldiers exposed to sarin & cyclosarin during the first Gulf War
(1991) indicated that exposure was significantly associated with less proficient
neurobehavioral functioning on tasks involving fine psychomotor dexterity and
visuospatial abilities 45 years after exposure (Proctor et al, 2007).
o
Symptoms within seconds to hours of exposure:

Runny nose
Chest tightness
Low or high blood pressure
Watery eyes
Rapid breathing
Slow or fast heart rate
Drooling
Cough
Muscle fasiculations / twitching
Excessive sweating
Increased urination
Weakness
Eye pain
Diarrhea
Drowsiness
Blurred vision
Nausea, vomiting
Headache
Small or pinpoint pupils
Abdominal pain
Confusion
High Concentrations Can Cause:
Loss of consciousness
Seizures
Respiratory failure - leading to death (increased bronchial secretions, bronchoconstriction,
paralyzed diaphragm & central effects can all contribute to respiratory failure)
Routes of exposure:
o Following release of sarin into the air, people can be exposed through skin contact
or eye contact. They can also be exposed by breathing air that contains sarin.
o Sarin mixes easily with water, so it could be used to poison water. Following release
of sarin into water, people can be exposed by touching or drinking water that
contains sarin.
o Following contamination of food with sarin, people can be exposed by eating the
contaminated food
o A persons clothing can release sarin for about 30 minutes after it has come in
contact with sarin vapor, which can lead to exposure of other people
Treatment after exposure:
o Decontamination:
Remove & dispense of contaminated clothing As quickly as possible
Wash skin with large amounts of soap and water
Rinse the eyes with plain water for 10 to 15 minutes if they are burning or if
vision is blurred
If sarin has been swallowed, do not induce vomiting or give fluids to drink
o Give atropine and pralidoxime STAT as antidotes
Supportive measures such as assisted ventilation, diazepam for convulsions,

phentolamine for 2-PAM induced hypertension
Notes:
o Sarin is a clear, colorless, and tasteless liquid that has no odor in its pure form
o Sarin can evaporate into a vapor (gas) and spread into the environment
o Sarin is also known as GB
o Sarin and other nerve agents may have been used in chemical warfare during the
Iran-Iraq War in the 1980s
o Sarin was used in two terrorist attacks in Japan in 1994 and 1995. These
attacks & their outcomes have been described in an article by Yanagisawa et al
(2006).
o
References:
1. Center for Disease Control & Prevention (Sarin - GB)
2. Hurst CG, Newmark J, Romano JA Jr (2012): Chemical Bioterrorism (Chapter 222). In:
Harrison's Principles of Internal Medicine Vol 2 18e. Fauci, Brauwald, Kasper, Hauser,
Longo, Jameson & Loscalzo. Vol 2 18e. McGraw Hill. (ISBN 978-0-07174889-6)
3. Morgan DL, Ortiz C (2011): Nuclear, Biologic & Chemical Agents; Weapons of Mass
Destruction. (Chapter 3). In: Current Diagnosis & Treatment: Emergency Medicine 7e.
McGraw-Hill. (Access Medicine)
4. Proctor SP, Heaton KJ, Heeren T, White RF: Effects of sarin and cyclosarin exposure during
the 1991 Gulf War on neurobehavioral functioning in US army veterans. Neurotoxicology
27(6): 931-939.
5. Yanagisawa N, Morita H, Nakajima T: Sarin experiences in Japan: Acute toxicity and longterm effects. Journal of the Neurological Sciences 249(1):76-85, 2006
Keywords
Soman (GD)
Drug Class: Organophosphate Chemical Warfare Agent classified as a Nerve Agent

o Inhibits the destruction of acetylcholine by cholinesterase
o Aging occurs within a half-life of only 2 minutes with soman
o Rapid aging can make it almost impossible to give pralidoxime rapidly enough to be
beneficial after the first noticeable detection of symptoms of poisoning are felt
Effects:
o Same as sarin
Routes of exposure:
o Same as sarin
Treatment after exposure:
o Same as sarin except pralidoxime may be ineffective due to rapid aging caused by
soman.
Notes:
o Soman is a clear, colorless, tasteless liquid with a slight camphor odor (for example,
Vicks Vapo-Rub) or rotting fruit odor
o More difficult to vaporize compared to Sarin
o It can become a vapor if heated
o Also known as GD
References:
o Center for Disease Control & Prevention (Soman - GD)
Hurst CG, Newmark J, Romano JA Jr (2012): Chemical Bioterrorism (Chapter 222).

In: Harrison's Principles of Internal Medicine Vol 2 18e. Fauci, Brauwald, Kasper,
Hauser, Longo, Jameson & Loscalzo. Vol 2 18e. McGraw Hill. (ISBN 978-0-071748896)
Morgan DL, Ortiz C (2011): Nuclear, Biologic & Chemical Agents; Weapons of Mass
Destruction. (Chapter 3). In: Current Diagnosis & Treatment: Emergency Medicine
7e. McGraw-Hill. (Access Medicine)
Keywords
VX
Drug Class: Chemical Warfare Agent classified as a Nerve Agent

Mechanism of Action & Effects:
o Same as soman & sarin
Routes of exposure:
o VX can be absorbed through the eyes or the skin of the victim
o As little as one drop of VX on the skin can be fatal (as compared to 1 to 10 mls of
sarin or soman)
o The LD50 for humans is estimated to be ~10 mg
Notes:
o Amber (honey brown) colored, tasteless & odorless, oily liquid with low volatility
unless temperatures are high
o The V of VX signifies it very long persistence compared to sarin and
soman
o VX decomposes at a rate of ~ 5% a month at 71 C
o VX-inhibited cholinesterase can be reactivated by 2-PAM for as long as 48 hours
(Sidell & Groff : The reactivatibility of cholinesterase inhibited by VX and sarin in
man. Toxicol Applied Pharmacol 27(2):241-52, 1974)
References:
o Center for Disease Control & Prevention (VX)
o Hurst CG, Newmark J, Romano JA Jr (2012): Chemical Bioterrorism (Chapter 222).
o Morgan DL, Ortiz C (2011): Nuclear, Biologic & Chemical Agents; Weapons of Mass
Destruction. (Chapter 3). In: Current Diagnosis & Treatment: Emergency Medicine
7e. McGraw-Hill. (Access Medicine)
VX is not fluorescent green as depicted in the movie The Rock (1996 - with Nicholas Cage &
Sean Connery). It is amber colored (CDC Facts About VX). Also (as depicted in the movie)
stabbing yourself in the heart with the antidote (atropine/2-PAM) contained in the military Mark 1
kit auto-injectors is probably not wise, although it certainly is dramatic. The auto-injectors are
designed to be applied to a victim's thigh.
Keywords
Cholinesterase Regenerator
Pralidoxime (2-PAM)
Trade Names: generic, Protopam

Drug Class: cholinesterase regenerator, oximes
o regenerates cholinesterase activity that has become inhibited by an
organophosphate compound (but is most effective when given before chemical
aging between the organophosphate & cholinesterase enzyme has occurred).
o The oxime group (=NOH) in pralidoxime has a very high affinity for the
phosphorous atom of oragnophosphates and can cause the bond between
the organophosphate agent and the cholinesterase to hydrolyze if the
complex has not aged or stabilized due to the spontaneous loss of an alkyl
group from the organophosphate compound.
o Pralidoxime's effect on non-aged organophosphate-enzyme complexes causes a
reactivation of cholinesterase activity.
o Because of it's positive charge, pralidoxime does not cross the blood-brain barrier.
Organophosphate aging and the effect of pralidoxime to regenerate

acetylcholinesterase (AChE).
Indications:
o Used together with atropine to treat poisoning caused by
organophosphate cholinesterase inhibitors that are used as pesticides (e.g.,
diazinon, malathion, mevinphos, parathion) or in chemical warfare (e.g. the nerve

gas sarin).
o 2-PAM is not as effective against the chemically different carbamate type
cholinesterase inhibitors (such as neostigmine and pyridostigmine) because
carbamates do not have phosphate groups and do not undergo aging.
o Because pralidoxime is less effective in relieving depression of the respiratory center,
atropine is always required concomitantly to block the effect of accumulated
acetylcholine at this site.
o Pralidoxime relieves muscarinic signs and symptoms, salivation, bronchospasm, etc.,
but this action is relatively unimportant since atropine is adequate for this purpose.
Relative Contraindications:
o Much less effective against against nerve gases that have already
inhibited cholinesterase and aged to a resistant form .
o Pralidoxime may make the symptoms of myasthenia gravis worse.
o Pralidoxime's effects may be intensified in patients with kidney disease.
Side Effects:
o Excessive doses can induce neuromuscular weakness & other adverse effects
Pharmacokinetics:
o typically given by i.v. infusion over 15-30 min, although multiple doses given over
several days may produce beneficial effects in severe poisoning.
References:
o Hurst CG, Newmark J, Romano JA Jr (2012): Chemical Bioterrorism (Chapter 222).
o rxlist.com (Protopam )
Keywords
Muscarinic Cholinolytics
Atropine
Trade Name: generic, Atropen

Drug Class: Muscarinic blocker (nonselective)
o Competitive muscarinic receptor antagonist (of all muscarinic receptor
subtypes).
Its antagonism which can be overcome by increasing the concentration of
acetylcholine at receptor sites of the effector organ (e.g., by using
anticholinesterase agents which inhibit the enzymatic destruction of
acetylcholine)
o Recent evidence indicates that muscarinic receptors are constitutively
active, and most drugs that block the actions of acetylcholine are inverse
agonists (including atropine) that shift the equilibrium to the inactive
state of the receptor ( Pappano, 2012)
The receptors antagonized by atropine are the peripheral structures that are
stimulated or inhibited by muscarine (i.e., exocrine glands, smooth and cardiac
muscle).
o Responses to postganglionic cholinergic nerve stimulation also may be inhibited by
atropine but this occurs less readily than with responses to injected (exogenous)
choline esters.
Indications:
1. preanesthetic medication: to prevent or reduce secretions of the respiratory tract
that occur during surgery where general anesthetics are used
2. to restore cardiac rate and arterial blood pressure during anesthesia when
vagal stimulation produced by intra-abdominal surgical traction causes a sudden
decrease in pulse rate and cardiac output.
3. to reduce the degree of atrioventricular (A-V) heart block when increased
vagal tone is a major cause (e.g. as in cases of digoxin toxicity, or following an
inferior MI).
4. to prevent severe bradycardia and syncope due to a hyperactive carotid sinus reflex.
5. as an antidote (with external cardiac massage) for cardiovascular collapse from the
injudicious use of a choline ester (cholinergic) drug.
6. treatment of anticholinesterase poisoning from organophosphorus
insecticides.
7. antidote for the rapid type of mushroom poisoning due to the presence of
the muscarine that is found in certain fungi such as Amanita muscaria
8. may improve the tremor & rigidity of Parkinsonism
9. as an eye-drop medication to cause prolonged relaxation of over-contracted eye
muscles due to chronic eye inflammation. Atropine's effects last for more than a
week (7-10 days of mydriasis, & ~2 weeks of cycloplegia) - this is why it is not used
for routine retinal exams requiring mydriasis.
Note: shorter acting antimuscarinics such as homatropine, cyclopentolate or
tropicamide are typically used to produce mydriasis during routine eye exams,
as illustrated below (Wikipedia commons).
o
Contraindications:
o Atropine generally is contraindicated in patients with glaucoma, pyloric
stenosis or prostatic hypertrophy, except in doses ordinarily used for preanesthetic
medication.
o Atropine Sulfate Injection, USP should be used with caution in all individuals over 40
years of age
Side Effects:
o Most of the side effects of atropine are directly related to its antimuscarinic action.
o Dryness of the mouth, blurred vision, photophobia and tachycardia
commonly occur with chronic administration of therapeutic doses.
o Anhidrosis may occur and produce heat intolerance or impair temperature regulation
in persons living in a hot environment.
o Constipation and difficulty in micturation may occur in elderly patients.
o Occasional hypersensitivity reactions have been observed, especially skin rashes
which in some instances progressed to exfoliation.
o Occasionally, therapeutic doses dilate cutaneous blood vessels, particularly in the
blush area (atropine flush).
Marked excitement and convulsions may occur with toxic doses (in comparison,
scopolamine has greater CNS effects). The fatal adult dose of atropine is not known;
200 mg doses have been used and cumulative doses as high as 1000 mg have been
given.
o Remember the phrase: Blind as a bat, Mad as a hatter, Dry as a bone, Red as
a beet, Hot as hell, Full as a Flask (see the Antimuscarnics wiki module for the
mechanisms responsible for these side effects).
Pharmacokinetics:
o Administered i.v., s.c. or i.m..
o Atropine disappears rapidly from the blood following injection (half life is 2 hrs) and
is distributed throughout the body.
o Much of the drug is destroyed by enzymatic hydrolysis, particularly in the liver; from
13 to 50% is excreted unchanged in the urine. Traces are found in various
secretions, including milk.
o Atropine readily crosses the placental barrier and enters the fetal circulation.
o Atropine's effect on parasympathetic function declines rapidly in all organs except
the eye. Effects on the iris and ciliary muscle persist for several days.
Drug Interactions:
o Concomitant administration of other drugs having anticholinergic effects (TCA's,
antihistamines) may precipitate the complications listed above.
References:
o Pappano A (2012): Cholinoceptor-Blocking Drugs. (Chapter 8). In: Basic and Clinical
Pharmacology. 12e. B Katzung, SB Masters AJ Trevor (Editors)
o rxlist.com (Atropine)
o
Keywords
Scopolamine
Trade Names: generic, Transderm Scop

Drug Class: Antimuscarinic (competitive antagonist)
o Antimuscarinic drug having more marked central effects, producing drowsiness
and amnesia in sensitive individuals.
Indications:
1. Prevention of nausea and vomiting associated with motion sickness and the use of
opioid analgesics (e.g. following surgery). The patch should be applied only to skin
in the postauricular area.
2. To produce mydriasis & cycloplegia in diagnostic procedures. For some pre- and
postoperative states when a mydriatic and cycloplegic state is needed in treatment
of iridocyclitis. It blocks the responses of the sphincter muscle of the iris and the
accommodative muscle of the ciliary body to cholinergic stimulation, producing
pupillary dilation (mydriasis) and paralysis of accommodation (cycloplegia).
3. Reduction of the tremor of Parkinson's disease.
Contraindications:
o Patients with angle-closure (narrow angle) glaucoma, or history of hypersensitivity to
scopolamine.
Side Effects:
o Therapeutic doses can cause drowsiness & amnesia, dry mouth, transient
impairment of eye accommodation, including blurred vision and dilation of the
pupils.
Toxic doses can cause excitement, agitation, hallucinations & coma (more likely than
with atropine).
Pharmacokinetics:
o Scopolamine is rapidly and fully distributed into the CNS where it has greater effects
than most other antimuscarinics.
o Following patch removal, plasma levels decline in a log linear fashion with an
observed half-life of 9.5 hours.
o Less than 10% of the total dose is excreted in the urine as parent and metabolites
over 108 hours.
o Scopolamine should be used with care in patients taking other drugs that are
capable of causing CNS effects such as sedatives, tranquilizers, or alcohol.
o Special attention should be paid to potential interactions with drugs having
anticholinergic properties; e.g., other belladonna alkaloids, antihistamines (including
meclizine), tricyclic antidepressants, and muscle relaxants.
References:
o rxlist.com (Transderm-Scop )
o
Keywords
Ipratropium bromide
Trade Name: Atrovent

Drug Class: Antimuscarinic
o A synthetic quaternary analog of atropine
Indications:
o A bronchodilator for maintenance treatment of bronchospasm associated with
asthma, chronic obstructive pulmonary disease, including chronic bronchitis
and emphysema.
o It does not have the same efficacy in every patient, because patients differ in the
extent of muscarinic involvement in their asthmatic symptoms.
o Administered either alone or with other bronchodilators, especially beta adrenergics,
Contraindications:
o Ipratropium bromide inhalation aerosol is contraindicated in patients with a history
of hypersensitivity to soya lecithin or related food products such as soybean and
peanut.
Side Effects:
o Tachycardia, palpitations, eye pain, urinary retention, urinary tract infection and
urticaria.
o A single case of anaphylaxis thought to be possibly related to ipratropium bromide
has been reported.
o Cases of precipitation or worsening of narrow-angle glaucoma and acute eye pain
have been reported.
Pharmacokinetics:
o Given as an inhaled medication.
o The bronchodilation following inhalation of ipratropium bromide is primarily a local,
site-specific effect, not a systemic one.
o Much of an administered dose is swallowed but not absorbed, as shown by fecal
excretion studies.
The half-life of elimination is about 1.6 hours after intravenous administration.

Ipratropium bromide is minimally (0 to 9% in vitro) bound to plasma albumin and
1-acid glycoproteins. It is partially metabolized.
References:
o rxlist.com (Atrovent HFA )
o
o
Keywords
Glycopyrrolate
Trade Name: Robinul

Drug Type: A quaternary analog of atropine
o The same as atropine but without significant CNS effects
o It has a quaternary structure & does not cross the Blood-Brain-Barrier.
Indications:
1. as a pre-op medication to reduce salivary & respiratory secretions, as well
as the volume and acidity of gastric secretions, and to block cardiac vagal reflexes
during intubation & induction of general anesthesia.
2. used along in combination with neostigmine to reverse the effects of nondepolarizing skeletal muscle relaxants at the conclusion of surgery.
3. as an adjunctive drug for treatment of peptic ulcer when rapid anticholinergic
effect is desired, or when oral medication is not tolerated.
Pharmacokinetics:
o Given parenterally.
o When given i.v., its onset of action is ~1 minute
o When given i.m. it's onset of action occurs in 15-30 mins, with peak effects in 30-45
mins
o The vagal blocking effects last for 2-3 hrs, and decrease in salivation for up to 7 hrs
(longer than for atropine)
Side Effects:
o Similar to atropine (w/o CNS component) - e.g. dry mouth, blurred vision,
photophobia due to mydriasis, cycloplegia, tachycardia, decreased sweating. Cases
of (rare) malignant hyperthermia have been reported.
References:
o Morgan GE Jr, Mikhail MS, Murray MJ (2006): Anticholinergic Drugs (Chapter 11). In:
Clinical Anesthesiology 4e. Morgan GE Jr, Mikhail MS, Murray MJ (Editors). McGrawHill (Access Medicine)
o rxlist.com (Robinul )
Keywords
Nicotinic Cholinolytics
Trimethaphan
Trade Name: Arfonad
Drug Class: Short acting, nondepolarizing ganglionic blocker

o Selectively blocks the ganglionic subtype of nicotinic receptor
Indications:
o Treatment of hypertensive emergencies
o Treatment of & dissecting aortic aneurysm
o To produce controlled hypotension in neurosurgery to reduce bleeding in the
operative field, and in patients undergoing electroconvulsive therapy
Side Effects:
o The opposite of predominant tone (reflecting its loss):
cycloplegia
hypotension
postural (orthostatic) hypotension
tachycardia
decreased GI motility
hesitancy in urination & urinary retention
Pharmacokinetics:
o Inactive orally, given by i.v. infusion
o Trimethaphan is a quaternary drug that does not cross the blood brain barrier (in
contrast to mecamylamine, another ganglionic blocker that produces CNS effects
such as tremor, choreiform movements, and mental aberrations)
Notes:
o Another similar ganglionic blocker that is orally effective is mecamylamine
(Inversine ). Their effects on autonomic parameters (e.g. loss of predominant tone
& block of reflexes ) are similar, although their side effect profiles are slightly
different due to different effects on the CNS.
References:
Pappano A (2012): Cholinoceptor-Blocking Drugs. (Chapter 8). In: Basic and Clinical
Drugs.com (Trimehtaphan)
rxlist.com (Mecamylamine)
Keywords
d-Tubocurarine (Prototype Nondepolarizing

Neuromuscular Blocker)
Trade Name: generic

Drug Class: Nondepolarizing neuromuscular blocking agent (prototype)
o There are 3 mechanisms by which nondepolarizing neuromuscular blockers can
contribute to skeletal muscle relaxation:
1. At low concentrations they compete with acetylcholine (ACh) for
binding to postsynaptic nicotinic receptor sites in the skeletal muscle
neuro-muscular junction.
2. Nondepolarizing relaxants also interfere with presynaptic release of ACh
from motor nerve endings by still poorly understood mechanism(s). Both
block of Na channels and block of pre-synaptic nicotinic autoreceptors have
been implicated. The presynaptic nicotinic receptors have a different subunit
composition compared to the muscle-type nicotinic receptors.
3. At higher concentrations they can also produce a more intense motor

blockade by blocking the pore of the nicotinic receptor-channel complex.
Contraindications:
o Clients in whom release of histamine is hazardous. Use with caution during
pregnancy and lactation and in children.
Side Effects:
o Allergic reactions.
o Of the nondepolarizing neuromuscular blockers, d-tubocurarine causes the
most histamine release by a direct effect on mast cells. Histamine release can
cause bronchospasm, hypotension, salivary secretions.
o High doses of d-tubocurarine (& to a lesser extent other non-depolarizing blockers)
can produce ganglionic blockade, which can contribute to producing hypotension.
Pharmacokinetics:
o Given by injection (i.m., i.v.).
o Narrow margin between therapeutic dose and toxic dose.
o Onset, IV: 1 min; IM: 15-25 min. Time to peak effect 2-5 min.
o Duration, IV: 80-120 min. t1/2: 1-3 hr.
o About 43% excreted unchanged in urine.
Notes:
o d-tubocurarine is the prototype non-depolarizing skeletal muscle relaxant. It is now
rarely used, but is sometimes mentioned on board/shelf exams.
o Its muscle relaxant properties are qualitatively similar to the other newer nondepolarizing relaxants such as pancuronium, vecronium, rocuronium (to name just a
few).
o The newer drugs have fewer side effects and superior pharmacokinetic profiles.
o Tubocurarine is the main active ingredient in the South American arrow poison curare.
References:
www.healthdigest.org
Kruidering-Hall M, Campbell L (2012): Skeletal Muscle Relaxants. (Chapter 27). In: Basic
and Clinical Pharmacology. 12e. B Katzung, SB Masters AJ Trevor (Editors)
Access Medicine - Neuromuscular Blocking Agents (Chapter 9). In: Clinical Anesthesiology.
4e. Morgan GE Jr, Mikhail MS, Murray MJ (Editors). 2006.
Encyclopedia Britannica
Jonsson M, Gurley D, Dabrowski M, Larsson O, Johnson EC: Distinct pharmacologic
properties of neuromuscular blocking agents on human neuronal nicotinic acetylcholine
receptors. Anesth 105:521-33, 2006.
Keywords
Other Nondepolarizing Neuromuscular Blockers

The ideal skeletal muscle relaxant should have:
a rapid onset of action (to allow rapid intubation)

a duration of action similar to the duration of the interventional procedure (endoscopy,
surgery)
no side effects
Tubocurarine - the original nondepolarizing relaxant has:
relatively slow onset of action (4-6 mins)

long duration of action (80-120 mins)
significant side effects - histamine release from mast cells - causing bronchospasm,
hypotension, salivary secretions.
Examples of Newer Agents that have different durations of actions & fewer side
effects:
Pancuronium: virtually no histamine release, but blocks muscarinic receptors. Similar

onset of action & duration as tubocurarine.
Rocuronium: rapid onset (1-2 mins) & intermediate duration (30-60 mins). An alternative
for succinylcholine in emergency cases where rapid-induction of anesthesia is needed.
Vecuronium: intermediate onset of action (2-4 mins) & duration of action (25-40 mins).
Nomenclature Heads Up:
Steroid derivatives (pancuronium, pipercuronium, rocuronium, etc) end in curonium

Isoquinolone derivatives (atracurium, doxacurium, mivacurium, etc) end in curium
References:
o Hibbs RE, Zambon AC (2011): Agents Acting at the Neuromuscular Junction and
Autonomic Ganglia (Chapter 11). In: Goodman & Gilman's Pharmacological Basis for
Therapeutics. 11e. McGraw-Hill (Access Medicine)
o Kruidering-Hall M, Campbell L (2012): Skeletal Muscle Relaxants. (Chapter 27). In:
Basic and Clinical Pharmacology. 12e. B Katzung, SB Masters AJ Trevor (Editors)
Keywords
Depolarizing Neuromuscular Blocker /

Relaxant
Succinylcholine
Trade Name: Anectine

Drug Class: Depolarizing Neuromuscular Blocker
o In the motor endplate it combines with nicotinic receptors to produce depolarization
which can be observed as uncontrolled focal muscle contractions (fasciculations).
Subsequent transmission across the NMJ is inhibited as long as succinylcholine
remains at the nicotinic receptor sites.
A depolarized post-junctional membrane (resulting in inactivation of Na
channels) causes the postjunctional membrane to become unresponsive to
ACh released by motor neurons. This is referred to as Phase I block &
produces a characteristic reduction in contractile response (with no fade)
during a train of four stimuli.
o In less than a minute after IV administration a flaccid paralysis develops due to
the development of a desensitized state where the membrane becomes repolarized,
but insensitive to ACh (due to receptor desensitization). This is referred to as

Phase II block and responds to a train of four stimuli with a fade pattern
similar to that produced by non-depolarizing neuromuscular blockers.
o Succinylcholine's effects at muscarinic & nicotinic receptors outside of the NMJ are
responsible for numerous side effects.
o With a single IV dose, the period of flaccid paralysis lasts less than 10 minutes, and
is terminated due to rapid hydrolysis of succinylcholine by cholinesterase in the
plasma & liver.
Indications:
o Adjunct to general anesthesia to facilitate endotracheal intubation and relax skeletal
muscle during surgery or mechanical ventilation.
o It has a more rapid onset of action compared to most nondepolarizing
neuromuscular blockers, making it a drug of choice for emergency cases where
rapid endotracheal intubation is necessary.
Contraindications:
o Genetic disorders of plasma pseudocholinesterase
o Family history of malignant hyperthermia
o Recent burns or trauma
o Myopathies with elevated CPK levels
o Acute narrow-angle glaucoma or penetrating eye injuries
Side Effects:
o Succinylcholine's stimulatory effect can cause hyperkalemia. It should not be given
to patients 24 to 72 hrs after major burns or trauma because it may cause acute
hyperkalemia, hyperkalemic rhabdomyolysis & cardiac arrest.
o It has also produced acute hyperkalemia & cardiac arrest in otherwise healthy boys
with unrecognized muscular dystrophy, causing the FDA to issue a warning about its
use in children (it should not be used in children except for emergency control of the
airway).
o Heavily muscled patients can suffer from muscle pain due to muscle fasiculations, as
well as an increased risk for regurgitation & aspiration of gastric contents caused by
increases in intragastric pressure.
o Succinylcholine can cause a rapid increase in intraocular pressure due to effects on
ocular blood vessels & myofibrils.
o It can cause cardiac arrhythmias (increase or decrease in heart rate) because of its
effects on muscarinic receptors and nicotinic-ganglionic receptors.
o There is an increased risk for potentially fatal malignant hyperthermia.
Pharmacokinetics:
o Given i.v. or i.m. Metabolized by plasma pseudocholinesterase, duration of action 430 min depending on route of administration.
o Aminoglycoside antibiotics (additive skeletal muscle blockade)
Notes:
o Succinylcholine is the only depolarizing type NMJ blocker in clinical use in the USA
References:
o Hibbs RE, Zambon AC (2011): Agents Acting at the Neuromuscular Junction and
Autonomic Ganglia (Chapter 11). In: Goodman & Gilman's Pharmacological Basis for
Therapeutics. 12e. McGraw-Hill (Access Medicine).
o Kruidering-Hall M, Campbell L (2012): Skeletal Muscle Relaxants. (Chapter 27). In:
Basic and Clinical Pharmacology. 12e. B Katzung, SB Masters AJ Trevor (Editors)
o Morgan GE Jr, Mikhail MS, Murray MJ (2006): Neuromuscular Blocking Agents
(Chapter 9) In: Clinical Anesthesiology. 4th Edition. Morgan GE Jr, Mikhail MS,
Murray MJ (Editors). McGraw-Hill (Access Medicine).
o rxlist.com (Anectine )
Keywords
Drugs Effecting the Sympathetic Nervous

System
Methyldopa
Trade Name: generic (Aldomet )

Drug Class: Antihypertensive
o The antihypertensive effect of methyldopa is believed to be due to its metabolism to
alpha-methylnorepinephrine, which then lowers arterial pressure by:
stimulation of central inhibitory 2 adrenergic receptors
false neurotransmission and/or
reduction of plasma renin activity
Indications:
o Treatment of hypertension during pregnancy as a replacement for ACE
inhibitors & ARBs (which are more efficacious, but are strongly contraindicated in
pregnancy).
The patient can be switched back to an ACE inhibitor or ARB once pregnancy
is over
Notes:
o Methyldopa is the L-isomer of alpha-methyldopa
References:
o Benowitz NL (2012): Antihypertensive Agents (Chapter 11). In: Basic and Clinical
Pharmacology. 12e. B Katzung, SB Masters AJ Trevor (Editors). McGraw-Hill (Access
Medicine).
o rxlist.com (Aldomet )
Keywords
Reserpine
Trade Name: generic

Drug Class: Antihypertensive (catecholamine depletor)
o A selective inhibitor of the catecholamine vesicular monoamine uptake
transporter (VMAT) that transports norepinephrine & epinephrine into presynaptic
vesicles found in sympathetic nerve terminals
o Produces a depletion of releasable neuronal catecholamine stores
o Reserpine's effects produce a reduction in blood pressure due to a decreased cardiac
output & decreased peripheral vascular resistance
Indications:
o Hypertension
Side Effects:
o Sedation
o Depression (suicidal tendencies)
o Parkinsonism symptoms
Pharmacokinetics:
Note:
Reserpine readily crosses the blood brain barrier & depletes cerebral catecholamine
stores. This can cause side effects such as those listed above.
Reserpine is the active ingredient of a herbal tranquillizer from Rauwolfia serpentina

discovered by ancient Indian physicians.
o Clinically, reserpine is primarily of historical importance, although it is used in
animal experiments to deplete catecholamine levels.
References:
Pharmacology. 12e. B Katzung, SB Masters AJ Trevor (Editors. McGraw-Hill (Access
Medicine).
o Medpedia.com (Clinical: Reserpine)
o
Keywords
Octopamine
Drug Class: False neurotransmitter.

o Octopamine replaces norepinephrine in sympathetic neurons with chronic
use of monoamine oxidase inhibitors
Dopamine beta-hydroxylase converts tyramine to octopamine
Octopamine can be taken up into storage vesicles in nerve
terminals, and then be released by nerve stimulation
Octopamine exerts only a small effect on postsynaptic receptors
compared to norepinephrine (hence the designation false transmitter)
Notes:
o Octopamine typically exists in only trace amounts in the mammalian CNS, but
accumulates when MAO is inhibited (e.g. by MAO inhibitors).
o First identified in the octopus
o Octopamine plays an important role in the innvertebrate nervous system where its
role is analogous to that of norepinephrine (NE) in vertebrates, and it is responsible
for the fight or flight effect and fat mobilizing.
o Cocaine blocks its reuptake in insects, and thereby has insecticidal properties that
are protective to the coca plant.
References:
o Katzung BG (2012): Introduction to Autonomic Pharmacology (Chapter 6). In: Basic
& Clinical Pharmacology. 12e. B Katzung, SB Masters AJ Trevor (Editors. McGraw-Hill
(Access Medicine).
o Roeder T (1999): Octopamine in Invertebrates. Progress in Neurobiology. 59(5):533561.
o Wikipedia
Keywords
Bretylium
Trade Name: generic

Drug Class: Antiarrhythmic
o Interferes with the neuronal release of catecholamines (after an initial phase
of causing the release of catecholamines)
o Bretylium also lengthens the duration and effective refractory period in heart tissue
(a Class III effect), an effect that is most pronounced in ischemic cells (which have
shortened action potential durations)
Indications:
o No longer available in the United States
o Previously used for attempted resuscitation from ventricular fibrillation after lidocaine
and cardioversion have failed
Side Effects:
o Precipitation of cardiac arrhythmias at the onset of drug therapy due to its ability to
cause the initial release of catecholamines (when used as an antiarrhythmic).
o Postural hypotension (a sympathoplegic side effect)
o Nausea & vomiting
o Digitalis toxicity may be aggravated by the initial release of norepinephrine caused
by Bretylium.
o The pressor effects of catecholamines such as dopamine or norepinephrine are
enhanced (mechanism unclear)
Note:
o Considered a drug of last choice as an antiarrhythmic
o Primarily of historical significance
Reference:
o rxlist.com (Bretylium)
Keywords
Guanethidine
Trade Name: generic

Drug Class: Antihypertensive, Adrenergic Neuron-blocking Agent
o In high doses can cause profound sympathoplegia or pharmacologic
sympathectomy
o Guanethidine has 4 mechanisms of action:
1. Causes an initial release of norepinephrine (tyramine-like effect), followed
by replacement of norepinephrine by guanethidine in transmitter vesicles that
eventually causes a
2. Gradual depletion of norepinephrine stores in the nerve ending (a reserpinelike effect).
3. It's strong interaction with the nerve terminal transporter produces a
cocaine-like effect.
4. Inhibits the release of norepinephrine from nerve terminals (bretylium-like
effect).
It can produce an initial pressor effect (due to tyramine & cocaine like actions), but
later results in sympathoplegia (due to reserpine & bretylium like effects). This
pressor effect is greatly reduced or not observed when the drug is taken orally &
slowly absorbed.
Indications:
o Guanethidine is no longer available in the USA due to lack of availability, but is
available in the UK (wikipedia)
o Was used for severe cases of hypertension, either alone or as an adjunct drug
Contraindications:
o Guanethidine can cause a hypertensive crisis in patients with pheochromocytoma
due to the release of catecholamines (tyramine like action).
Side Effects:
o Postural hypotension, diarrhea (from increased GI motility), impaired ejaculation
Pharmacokinetics:
o Guanethidine is too polar to enter into the CNS, and hence has little or no CNS side
effects.
o Tricyclic antidepressants will decrease guanethidine's antihypertensive effects by
blocking its uptake into nerve terminals. Concurrent use with other
sympathomimetics (OTC cold medications) may produce hypertension.
Notes:
o Yes this is a dinosaur drug (hence the cartoon)
o Q1: Will you ever prescribe this drug? (Not in the USA)
o Q2: Is guanethedine a nice tool for understanding the pharmacology of the nerve
terminal? (Yes)
o Q3: Do I need to know it for the boards? (Extremely unlikely).
Reference:
o rxlist.com (Ismelin ) (no longer sold in the US under this trade name)
o
Keywords
Alpha Sympathomimetics
Clonidine
Trade Name: Catapres, Catapre-TTS, Duraclon

Drug Class: Alpha-2 Selective Adrenergic Agonist
o 2 adrenoreceptor agonist that produces its main therapeutic effect by
stimulating -2 receptors in the brain stem.
o This action results in reduced sympathetic outflow from the central nervous
system and in decreases in peripheral resistance, renal vascular resistance, heart
rate, and blood pressure.
o Selective for alpha-2 over alpha-1 receptors
Indications:
o treatment of hypertension
Contraindications:
o Hypersensitivity
Side Effects:
o Dry mouth, dizziness, constipation
Pharmacokinetics:
Clonidine acts relatively rapidly. The patients blood pressure declines within 30
to 60 minutes after an oral dose, the maximum decrease occurring within 2 to 4
hours.
o May potentiate the CNS-depressive effects of alcohol, barbiturates or other sedating
drugs.
o May produce bradycardia & depress sinus node function in patients on digitalis,
calcium channel blockers and beta-blockers.
References:
Pharmacology. 12e. B Katzung, SB Masters AJ Trevor (Editors). McGraw-Hill (Access
Medicine).
o rxlist.com (Catapres )
o
Keywords
Phenylephrine
Trade Names: generic, Neo-Synephrine

Drug Class: Alpha-1 Selective Agonist; Nasal decongestant
o A powerful postsynaptic -receptor stimulant with little effect on the beta receptors
of the heart.
o In therapeutic doses, it produces little if any stimulation of either the spinal cord or
cerebrum.
o A singular advantage of this drug is the fact that repeated injections produce
comparable effects.
Indications:
1. nasal spray to act as a decongestant to reduce the discomfort of hay fever &
the common cold by decreasing the volume of the nasal mucosa
2. given systemically for the maintenance of an adequate level of blood pressure
during spinal and inhalation anesthesia and for the treatment of vascular
failure in shock, shock-like states, and drug-induced hypotension, or hypersensitivity.
It is also employed to overcome paroxysmal supraventricular tachycardia, to prolong
spinal anesthesia, and as a vasoconstrictor in regional analgesia.
3. used as a mydriatic.
Contraindications:
o Hypertension
o Ventricular tachycardia
o Known hypersensitivity
Side Effects:
o Headache, reflex bradycardia, excitability, restlessness, and rarely arrhythmias
Pharmacokinetics:
o The route of administration varies with the indication.
o It can be given by nasal spray, s.c., i.m. or i.v. injection.
o It produces vasoconstriction that lasts longer than that of epinephrine and
ephedrine (lasting 20 minutes after intravenous and as long as 50 minutes
after subcutaneous injection).
o It is not a catechol and is not inactivated by COMT.
o The pressor effect of sympathomimetic pressor amines is markedly potentiated in
patients receiving monoamine oxidase inhibitors (MAOI)
References:
(Chapter 9). In: Basic and Clinical Pharmacology. 12e. B Katzung, SB Masters AJ
Trevor (Editors); McGraw-Hill (Access Medicine).
o rxlist.com (Neo-Synephrine )
Keywords
Beta Sympathomimetics
Isoproterenol
Trade Name: generic, Isuprel

Drug Class: Nonselective Beta Adrenergic Agonist (Sympathomimetic)
o Stimulates both 1 and 2 adrenergic receptors.
o Intravenous infusion of isoproterenol in humans lowers peripheral vascular
resistance, primarily in skeletal muscle but also in renal and mesenteric vascular
beds.
o Diastolic pressure falls. Systolic blood pressure may remain unchanged,
rise or fall (depending on the dose); mean arterial pressure typically falls;
See (Fig 9-6 in Katzung)
o Cardiac output is increased because of the positive inotropic and chronotropic effects
of the drug in the face of diminished peripheral vascular resistance.
o The cardiac effects of isoproterenol may lead to palpitations, sinus tachycardia, and
more serious arrhythmias.
o Isoproterenol relaxes bronchial smooth muscle.
Indications:
1. For mild or transient episodes of heart block that do not require electric shock or
pacemaker therapy.
2. For serious episodes of heart block and Adams-Stokes attacks (except when caused
by ventricular tachycardia or fibrillation).
3. For use in cardiac arrest until electric shock or pacemaker therapy, the treatments
of choice, are available.
4. For bronchospasm occurring during anesthesia.
5. As an adjunct to fluid and electrolyte replacement therapy and the use of other
drugs and procedures in the treatment of hypovolemic and septic shock, low cardiac
output (hypoperfusion) states, congestive heart failure, and cardiogenic shock.
Contraindications:
o May have a deleterious effect on the injured or failing heart (by increasing
myocardial oxygen requirements while decreasing effective coronary perfusion)
Side Effects:
o CNS:
Nervousness,
Headache
Dizziness
o Cardiovascular:
Tachycardia, ventricular arrhythmias
Palpitations
Angina
Hyper- or hypo-tension
Adams-Stokes attacks
Pulmonary edema
Pharmacokinetics:
o Isoproterenol is readily absorbed when given parenterally or as an aerosol. It is
metabolized primarily in the liver and other tissues by COMT.
o Isoproterenol is a relatively poor substrate for MAO and is not taken up by
sympathetic neurons to the same extent as are epinephrine and norepinephrine. The
duration of action of isoproterenol may therefore be longer than that of epinephrine,
but is still brief.
o Isoproterenol should be used with caution, if at all, when potent inhalational
anesthetics such as halothane are employed because of potential to sensitize the
myocardium to effects of sympathomimetic amines.
References:
o rxlist.com (Isuprel )
o
o
Keywords
Dobutamine
Trade Name: generic

Drug Class: Beta-1 Selective Sympathomimetic
o 1 selective adrenergic agonist.
o In animal studies, dobutamine produces less increase in heart rate and less decrease
in peripheral vascular resistance for a given inotropic effect than does isoproterenol
Indications:
o inotropic support in the short-term treatment of patients with cardiac
decompensation due to depressed contractility resulting either from organic
heart disease or from cardiac surgical procedures
Contraindications:
o Dobutamine is contraindicated in patients with idiopathic hypertrophic subaortic
stenosis and in patients who have shown previous manifestations of hypersensitivity
to dobutamine
Side Effects:
o A 10-20 mm increase in systolic blood pressure and an increase in heart rate of 5-15
beats/minute occurs in most patients
Pharmacokinetics:
o Given parenterally
o Onset of action of dobutamine is 1 to 2 minutes; however, with peak effect within 10
minutes; plasma half-life is 2 minutes
o The principal routes of metabolism are methylation of the catechol and conjugation
Drug Interactions:
o Do not add dobutamine to 5% Sodium Bicarbonate Injection or to any other strongly
alkaline solution. Because of potential physical incompatibilities, it is recommended
that dobutamine not be mixed with other drugs in the same solution
o Dobutamine should not be used in conjunction with other agents or diluents
containing both sodium bisulfite and ethanol
References:
Biaggioni I, Robertson D (2012): Adrenoceptor Agonists & Sympathomimetic Drugs

Katzung BG (2012): Drugs used in heart failure (Chapter 13). In: Basic and Clinical
Pharmacology. 12e. Katzung BG, Masters SB, Trevor AJ (Editors). McGraw-Hill /
Lange
rxlist.com (Dobutamine)
Keywords
Albuterol
Trade Name: Ventolin, Combivent, Proventil

Drug Class: Beta-2 Adrenergic Agonist (short acting)
o Selective 2 agonist. The prime action of beta-adrenergic drugs is to stimulate
adenyl cyclase, the enzyme which catalyzes the formation of cyclic AMP from ATP.
cAMP mediates the cellular responses
Indications:
o To produce bronchodilation
o Prevention and relief of bronchospasm related to asthma, and/or
exercise-induced bronchospasm
Contraindications:
o A history of hypersensitivity to albuterol
Side Effects:
o Manifestations of overdosage may include:
tremors
hypokalemia
hypo- or hypertension
angina & tachycardia with rates up to 200 beats/min
Pharmacokinetics:
o aerosol and capsule formulations. Albuterol is longer acting than isoproterenol
in most patients by any route of administration because it is not a substrate for the
cellular uptake processes for catecholamines or for COMT
o Less than 20% of a single albuterol dose is absorbed systemically following nebulizer
administration
o Albuterol does not readily cross the blood brain barrier
o Other sympathomimetic aerosol bronchodilators or epinephrine should not be used
concomitantly with albuterol
o Albuterol should be administered with extreme caution to patients being treated with
MAO inhibitors or tricyclic anti-depressants, since the action of albuterol on the
vascular system may be potentiated
Pharmwiki Sections: ANS Pharm & Pulmonary Pharm
References:
Medicine).
o rxlist.com (Proventil )
Keywords
Terbutaline
Trade Names Brethine, Bricanyl

Drug Class: Beta-2 Adrenergic Agonist
Mechanism of Action: same as albuterol
Indications:
o Prevention or Reversal of bronchospasm in patients with bronchial asthma and
reversible bronchospasm associated with bronchitis and emphysema
o In some patients the severity of bronchoconstriction can limit the delivery of drugs
by inhalation, making systemic drug administration necessary
Contraindications:
o hypersensitivity
Side Effects:
o Similar to those commonly seen with other sympathomimetic agents (e.g. albuterol)
o All these reactions are transient in nature and usually do not require treatment
Pharmacokinetics:
o typically given by s.c. injection
o same as with albuterol
References:
Medicine).
o rxlist.com (Terbutaline Sulfate)
Keywords
Indirectly Acting Sympathomimetics

Tyramine
Drug Class: Indirectly Acting Sympathomimetic (a byproduct of tyrosine metabolism)

o Tyramine is taken up into nerve terminals by NET (the catecholamine
reuptake transporter) and once inside the nerve terminal causes the
release of catecholamines by an unclear mechanism.
Pharmacokinetics:
o Tyramine is readily metabolized by MAO in the liver and is normally inactive when
taken orally because of a high first-pass effect (low bioavailability).
o If administered parentally, or if taken orally while taking MAO inhibitors, it
produces effects similar to norepinephrine, and can possibly cause a
hypertensive crisis.
o Tyramine causes the release of catecholamines from a small pool, and repeated
exposure may result in tachyphylaxis (a rapidly developing form of tolerance).
o Indirectly acting sympathomimetic amines must be taken up into the nerve terminal
to promote release. Thus agents that inhibit the NET uptake pump (e.g.
cocaine or imipramine) antagonize responses to indirectly acting
sympathomimetics.
o Agents that cause depletion of catecholamines from the sympathetic nerve terminals
(e.g., reserpine) can also antagonize indirectly acting agents (such as tyramine)
because there is a lack of catecholamines to be released. However, since

catecholamine depletion takes some time to develop, reserpine-like drugs must be
given several hours to days in advance of tyramine for this interaction to be
observable.
Note:
Tyramine is found in relatively high concentrations in fermented foods such as
cheese, sausage, pepperoni, salami, pickled or smoked fish & yeast
supplements. Small amounts are found in red wine & chicken liver as well; See
Table 9-5 in ( Biaggioni & Robertson (2012)).
Reference:
o
Keywords
Amphetamines (Drug Class)
Trade Names: Adderall, Dexedrine

Drug Class: CNS Stimulant, Indirectly Acting Sympathomimetic
o The D-isomer (Dextroamphetamine) is more potent than the L-isomer
2. PRIMARY MECHANISM: increases the release of monoamines
(norepinephrine & dopamine) from their storage sites in nerve terminals
Amphetamine causes the intracellular vesicular release of catecholamines
within the nerve terminal & reverses the membrane transporter
direction so that catecholamines are released into the synapse by reverse
transport rather than by ordinary excocytosis
3. may compete with monoamines for reuptake (competitive substrate)
4. weakly inhibits MAO
Indications:
o attention-deficit disorders
o narcolepsy
Contraindications:
o Lactation
o Contraindicated for long-term use for treating obesity (due to development of
tolerance &/or drug dependence)
Side Effects:
o nervousness
o insomnia
o palpitations
o hypertension
o hyperpyrexia
o headaches
o dizziness
o anorexia
o weight loss
o dryness of the mouth
Black Box Warnings: HIGH POTENTIAL FOR ABUSE

Amphetamines have a high potential for abuse. Administration for prolonged periods of time may
result in drug dependence. Misuse may cause sudden death and cardiovascular adverse events.
Pharmacokinetics:
o Dexedrine - PO, completely absorbed in 3 hr. Duration: PO, 4-24 hr; t1/2, adults:
10-12 hr; children: 6-8 hr.
Excreted in urine. Acidification will increase excretion, while alkalinization will

decrease it.
o MAO inhibitors will increase effects & toxicity
Notes:
o Schedule II drug with high abuse potential
References:
o rxlist.com (Dexedrine )
o rxlist.com (Adderall )
o
Keywords
Cocaine
Trade Name: generic

Drug Class: Topical Local Anesthetic, CNS Stimulant & Major Drug of Abuse
1. low concentrations block monoamine reuptake transport into nerve
terminals (All three types: NET, DAT & SERT) (Kd 0.3 uM for NET). NOTE:
Cocaine non-selectively blocks the membrane transporters for norepinephrine,
dopamine and serotonin (which are different gene products). The monoamine
membrane reuptake transporters are most dense in presynaptic nerve terminals, and
are different from the VMAT Vesicular MonoAmine Transporters on intracellular
storage vesicles that are blocked by reserpine.
2. At higher & more potentially toxic concentrations, cocaine also blocks Na
channels (local anesthetic action) (Kd 8 uM) & cardiac K channels (Kd
4 uM)(considered proarrhythmic), and eventually L-type Ca channels (at >30
uM) (Crumb & Clarkson, 1992; Clarkson et al, 1996; Ferreira et al., 2001).
Indications:
o Topical anesthesia of the upper respiratory tract (due to its combined
vasoconstrictor & local anesthetic properties)
o Use in Emergency Department as one ingredient in a topical anesthetic
solution called TAC (containing: Tetracaine, Adrenaline & Cocaine) that
is applied to a wound prior to cleaning & suturing
Contraindications:
o Hypersensitivity to ester anesthetics
Side Effects:
o Signs of systemic toxicity include signs of CNS stimulation:
tachycardia
hypertension
hyperthermia
mydriasis
seizures
o cardiac arrhythmias (multiple contributing variables: Na & K channel block,
possible coronary vasoconstriction)
GENERAL ANESTHESICS ANTAGONIZE COCAINE's SYSTEMIC EFFECTS

Administration of benzodiazepines (diazepam) is one of the first line treatments for cocaine
overdose. Benzodiazepines produce an increase in GABA-A mediated chloride current, which
hyperpolarizes neurons and produces widespread inhibition within the CNS. This can suppress
local anesthetic-induced seizure activity, and may reduce the CNS-mediated component of
cocaine's systemic effects (including the cocaine-induced increase in sympathetic outflow).
This type of antagonism can be observed when cocaine is administered to animals under the
influence of general anesthetics, which enhance the effects of GABA-A in the CNS. In this setting
very high potentially lethal plasma concentrations of cocaine (e.g. >30 uM) typically cause a fall
in blood pressure due to: a) a reduction in cardiac contractility due to cocaine block of L-type Ca
channels, and b) local anesthetic effects on vascular smooth muscle resulting in vasodilation.
Cocaine also does not typically produce an increase in heart rate under general anesthesia. These
cardiovascular effects are opposite of those typically seen in conscious animals (e.g.
simultaneous tachycardia & hypertension). This is because the simultaneous increase in blood
pressure and heart rate requires a functional CNS & result, in large part, from an increase in
sympathetic outflow from the CNS.
Black Box Warnings for Topical Cocaine: NOT FOR INJECTION OR OPTHALMIC USE
Not for injection or ophthalmic use.
Pharmacokinetics:
o A topical local anesthetic (its only FDA approved use)
o As a drug of abuse the HCl can be sniffed, taken orally or injected IV. The base form
(crack or freebase) is typically smoked
o Half life is ~50 min
o MAOI inhibitors would be expected to increase cocaine's effects & toxicity.
o Ethanol consumption will convert cocaine to cocaethylene, a derivative that
has a half life of 3-4 hours and shares a similar pharmacology as cocaine. Most
cocaine abusers consume ethanol to prolong their high. This may also increase
cocaine's cardiotoxicity.
Notes:
o One of the most addictive drugs known (Schedule II).
References:
o Clarkson CW, Xu YQ,Chang C,Follmer CH (1996): Analysis of the ionic basis for
cocaine's biphasic effect on action potential duration in guinea-pig ventricular
myocytes. J Mol Cell Cardiol 28:667678.
o Crumb WJ Jr, Clarkson CW (1992): Characterization of the sodium channel blocking
properties of the major metabolites of cocaine in single cardiac myocytes. J
Pharmacol Exp Ther 261:910917.
o Ferreira S, Crumb WJ Jr, Carlton CG, Clarkson CW (2001): Effects of Cocaine and Its
Major Metabolites on the HERG-Encoded Potassium Channel. J Pharmacol Exp Ther
299: 220-226.
o Luscher C (2012) Drugs of Abuse (Chapter 32). In: Basic & Clinical Pharmacology.
12e. Katzung BG, Masters SB, Trevor AJ (Editors). McGraw-Hill / Lange. (AccessMedicine)
o Prosser JM, Perrone J (2012): Cocaine, Methamphetamine, and Other Amphetamines
(Chapter 181). In: Harrison's Internal Medicine. 18th Edition. McGraw-Hill.
o rxlist.com (cocaine / topical)
Keywords
Imipramine
Trade Name: Tofranil

Drug Class: antidepressant (tricyclic amine)
o Blocks reuptake of norepinephrine & serotonin at nerve endings (therapeutic
effects)
o Na channel blocker (contributes to cardiotoxicity)
o Antimuscarinic (contributes to side effects)
o Antihistamine (contributes to side effects)
o Alpha receptor blocking properties (contributes to side effects)
o Several weeks to months are required for antidepressant effects to appear (or be
significantly greater than a placebo), although its direct effects (e.g. on reuptake)
develop within a matter of hours.
Indications:
o Depression
o Chronic pain
o Nocturnal enuresis (a pediatric indication - attributed to its antimuscarinic side
effects)
Contraindications:
o Drugs that inhibit monoamine oxidase (MAOI's) taken w/in 14 days, acute recovery
period after a myocardial infarction, or history of drug hypersensitivity
Side Effects:
o drowsiness
o dry mouth & eyes
o constipation
o orthotstatic hypotension
o mild tremor
o sweating
o agitation
o nausea
o tinnitus
o Overdose & Treatment: See Amitriptyline; potentially fatal disturbances of cardiac
conduction (widening of QRS), arrhythmias & seizures due to Na channel block
(cardiac & CNS)
Pharmacokinetics:
o PO, metabolized in the liver (P450 - 2D6); 16 hr half life
o Decongestants
o Local anesthetics w/ sympathomimetics
o Antihypertensives
o CNS depressants
o Drugs metabolized by P450-2D6
o Concomitant use of MAOI's can cause potentially fatal hyperpyretic crisis & seizures
Reference:
o DeBattista C (2012): Antidepressant Agents. Chapter 30. In: Basic & Clinical
Pharmacology. 12e. B Katzung, SB Masters AJ Trevor (Editors). McGraw Hill / Lange.
o rxlist.com (Tofranil )
Keywords
Mixed Direct & Indirect Acting

Sympathomimetic
Ephedrine
Trade Name: generic

Drug Class: Direct & Indirectly acting Sympathomimetic
o Ephedrine has both direct ( & ) adrenergic agonist effects and indirect
(amphetamine or tyramine-like) sympathomimetic effects
Indications:
o Diet suppressant
o Bronchodialator
o Decongestant
o CNS stimulant / energy supplement (increased risk of MI when used in high doses)
o Used as a pressor agent during spinal anesthesia when hypotension
frequently occurs (produces a longer pressor response compared to most other
directly acting agonists)
Contraindications:
o Cardiovascular disease
Side Effects:
o Higher than normal incidence of myocardial infarction, stroke and sudden
death (e.g. associated with chronic use of ephedrine-containing herbal
supplements)
o Hypertension, insomnia
Pharmacokinetics:
o tachyphylaxis develops with repeated dosing
Notes:
o Ephedrine occurs in various plants and is the active ingredient in Ma-huang, a
popular herbal medication
o In Dec 2003, the FDA issued a consumer alert to alert consumers to immediately
stop buying and using ephedra products. The alert was based mainly upon a review
of recent adverse event reports that indicated an increased risk of stroke,
myocardial infarction and sudden death in those using ephedra containing
dietary supplements. The FDA also announced a plan to ban the sale of all food
supplements containing ephedrine in the near future.
References:
o rxlist.com (Ephedrine)
Keywords
Alpha Blockers
Phenoxybenzamine
Trade Name: Dibenzyline
Drug Class: Noncompetitive & Nonselective 1 & 2 Antagonist

o A long-acting, adrenergic, -1 & -2 nonselective receptor blocking agent which can
produce and maintain chemical sympathectomy by oral administration
o Phenoxybenzamine binds covalently to receptors
o It increases blood flow to the skin, mucosa and abdominal viscera, and lowers both
supine and erect blood pressures
o It has no effect on the parasympathetic system
o (Although the clinical relevance is unclear, phenoxybenzamine also inhibits the
presynaptic reuptake of released norepinephrine, and blocks H-1 histamine,
acetylcholine and serotonin receptors as well as alpha receptors.)
Indications:
o Pheochromocytoma
o To control episodes of hypertension and sweating; if tachycardia is excessive, it may
be necessary to use a beta-blocking agent concomitantly
Contraindications:
o Conditions where a fall in blood pressure is undesirable
Side Effects:
o Postural hypotension
o Tachycardia
o Inhibition of ejaculation
o Nasal congestion
o Miosis
o Drowsiness
o GI irritation
o Shock (overdose)
Pharmacokinetics:
o The half-life of intravenously administered drug is approximately 24 hours
o Demonstrable effects with intravenous administration persist for at least 3 to 4 days,
and the effects of daily administration are cumulative for nearly a week
Drug Interactions:
o Interactions will occur with compounds that stimulate both - and -adrenergic
receptors (i.e., epinephrine) to produce an exaggerated hypotensive response and
tachycardia
References:
o Biaggioni I, Robertson D (2012): Adrenoceptor Antagonist Drugs (Chapter 10). In:
Basic and Clinical Pharmacology. 12e. B Katzung, SB Masters AJ Trevor (Editors);
McGraw-Hill (Access Medicine).
o rxlist.com (Dibenzyline )
Keywords
Phentolamine
Trade Name: Regitine

Drug Class: Nonselective Competititve Alpha Receptor Antagonist
o Phentolamine competitively blocks both 1 and 2 receptors
o It produces vasodilator effects on vascular smooth muscle, and less marked, positive
inotropic and chronotropic effects on cardiac muscle (baroreceptor reflex mediated)
o (Although the clinical significance is unclear, phentolamine also blocks H-1 and H-2
histamine receptors, serotonin and muscarinic receptors)
Indications:
o prevention or control of hypertensive episodes that may occur in a patient with
pheochromocytoma as a result of stress or manipulation during preoperative
preparation and surgical excision.
o prevention or treatment of dermal necrosis and sloughing following intravenous
administration or extravasation of norepinephrine.
o diagnosis of pheochromocytoma by the phentolamine blocking test
Contraindications:
o Myocardial infarction or history of myocardial infarction
o Coronary insufficiency, angina, or other evidence suggestive of coronary artery
disease
o Hypersensitivity to phentolamine or related compounds
Side Effects:
o Acute and prolonged hypotensive episodes
o Tachycardia
o Cardiac arrhythmias
Pharmacokinetics:
o Not well absorbed if taken orally, and is given either i.m. or i.v.
o It produces an -adrenergic block of relatively short duration (half-life in the blood of
19 minutes following intravenous administration)
References:
o rxlist.com (Phentolamine mesylate)
Keywords
Prazosin
Trade Names: generic, Minipress

Drug Class: Selective -1 Receptor Blocker, Antihypertensive
o Selectively blocks 1 adrenergic receptors (competitive)
o The peripheral vasodilator effect of prazosin is confined mainly to the level of the
resistance vessels (arterioles)
o Unlike conventional -blockers, the antihypertensive action of prazosin is usually not
accompanied by a marked reflex tachycardia (e.g. as compared to a nonselective -blocker)
Indications:
o Treatment of hypertension
It can be used alone or in combination with other antihypertensive drugs such
as diuretics or beta-adrenergic blocking agents
Side Effects:
o Dizziness
o Orthostatic hypotension
Pharmacokinetics:
o Taken orally. Following oral administration, human plasma concentrations reach a
peak at about three hours with a plasma half-life of two to three hours.
o The drug is highly bound to plasma protein.
References:
Benowitz NL (2012): Antihypertensive agents (Chapter 11). In: Basic and Clinical
Pharmacology. 12e. BG Katzung, SB Masters, AJ Trevor (Editors). Lange/McGrawHill.
Biaggioni I, Robertson D (2012): Adrenoceptor Antagonist Drugs (Chapter 10). In:
rxlist.com (Minipress )
Keywords
Doxazosin
Trade Names: generic, Cardura

o -1 selective blocker (similar to prazosin)
Indications:
o Benign Prostatic Hyperplasia (BPH) - treatment of urinary outflow
obstruction
Antagonism of alpha-1 receptors relaxes smooth muscle in the prostate and
bladder neck, which decreases urethral resistance & relieves outflow
obstruction in patients with BPH.
o Optional drug for treatment of Hypertension, but more useful in those patients
with both BPH and hypertension.
NOTE: Alpha blockers have not been shown to reduce morbidity and mortality
in patients with hypertension, in contrast to several other classes of
antihypertensive medications (such as thiazide diuretics, ACE inhibitors &
calcium channel blockers).
Pharmacokinetics:
o Long half life (22 hrs), once a day dosing.
References:
o Benowitz NL (2012): Antihypertensive agents (Chapter 11). In: Basic and Clinical
o rxlist.com (Cardura )
Keywords
Yohimbine
Trade Names: generic, Yocon

Drug Class: Selective Alpha-2 Receptor Blocker
o Blocks presynaptic 2 adrenergic receptors. This effect can increase
sympathetic outflow and potentiate the release of norepinephrine from nerve
endings, leading to activation of 1 and 1 receptors in the heart and peripheral
vasculature, with a consequent rise in blood pressure
Indications:
o Rarely used
Sometimes used in the treatment of orthostatic hypotension because it promotes

norepinephrine release through blockade of 2 receptors in both the central nervous
system and the periphery
o There is some evidence that it may be possibly effective in treating erectile
dysfunction & SSRI related sexual dysfunction in both men & women by unclear
mechanisms (NIH Medlineplus)
o Has been suggested to have aphrodisiac properties
Side Effects:
o Yohimbine exerts a stimulating action on the mood and may increase anxiety
o Yohimbine can reverse the antihypertensive effects of an 2 receptor agonist such
as clonidine, a potentially serious adverse drug interaction
References:
o rxlist.com (Yocon )
o
Keywords
Beta Blockers
Propranolol
Trade Names: generic, Inderal

Drug Class: Nonselective Beta Receptor Blocker
o Competitively blocks both 1 and 2 adrenergic receptors. When access to
-receptor sites is blocked by Propranolol HCl, the chronotropic, inotropic, and
vasodilator responses to beta-adrenergic stimulation are decreased proportionately.
Indications:
1. the management of hypertension. It may be used alone or used in combination
with other antihypertensive agents, particularly a thiazide diuretic.
2. the long-term management of patients with angina pectoris.
3. cardiac arrhythmias (atrial tachyarrhythmias induced by catecholamines, digitalis,
thyrotoxicosis, or associated with Wolff-Parkinson-White syndrome; for the
control of ventricular rate in patients with atrial flutter or fibrillation when digoxin
is ineffective or contraindicated, ventricular arrhythmias caused by catecholamines
or digoxin).
4. prevention of sudden death and reinfarction after an MI.
5. prophylactic treatment for the prevention of migraine headaches. (Not used for
acute aborting of migraine attacks)
6. treatment of systolic & diastolic forms of heart failure
Low doses of beta blockers reverse remodeling caused by chronic elevation of
sympathetic tone in patients with systolic heart failure. Ejection fraction
typically increases significantly after several months of low dose beta blocker
therapy.
Beta blockers are also indicated for treating diastolic heart failure (heart
failure with normal ejection fraction). Reducing the heart rate assists diastolic
filing, and reduced wall stiffness may help with diastolic filling.
7. management of hypertrophic subaortic stenosis
8. adjunct therapy with alpha blockers in treatment of pheochromocytoma

9. management of familial or hereditary essential tremor
Contraindications:
o Cardiogenic shock
o Sinus bradycardia and greater than first degree block
o Bronchial asthma
Side Effects:
o Bradycardia
o Congestive heart failure (a dose-dependent effect; low doses are used to treat
heart failure)
o Intensification of AV block
o Hypotension
o Paresthesia of hands
o Light-headedness
o Mental depression manifested by insomnia, lassitude, weakness, fatigue; sexual
dysfunction in men (see Refs 1, 4 & 5).
Pharmacokinetics:
o Propranolol is almost completely absorbed from the gastrointestinal tract, but a
portion is immediately bound by the liver
o Peak effect occurs in one to one-and-one-half hours. The biologic half-life is
approximately four hours.
o There is no simple correlation between dose or plasma level and therapeutic effect,
and the dose-sensitivity range as observed in clinical practice is wide. The principal
reason for this is that sympathetic tone varies widely between individuals. Since
there is no reliable test to estimate sympathetic tone or to determine whether total
beta blockade has been achieved, proper dosage requires titration.
o Patients receiving catecholamine-depleting drugs such as reserpine should be closely
observed if propranolol is administered.
o Caution should be exercised when patients receiving a beta blocker are administered
a calcium-channel blocking drug.
References:
0. Most beta blockers produce these CNS & sexual side effects to some extent. With
regards to how beta-blockers cause insomnia, it has been observed that beta-1
blockers decrease the release of melatonin, a compound involved in sleep &
circadian rhythm. To put this in context, ramelteon (Rozerum ) is a melatonin
agonist used to treat insomnia. You may have seen the TV ads in the past with a
man who could not sleep talking to Abe Lincoln, a talking beaver & other characters
"Your Dreams Miss You" Youtube video.
1. Benowitz NL (2012): Antihypertensive agents (Chapter 11). In: Basic and Clinical
2. Hume JR, Grant AO (2012): Agents used in cardiac arrhythmias (Chapter 14). In:
Basic and Clinical Pharmacology. 12e. Katzung BG, Masters SB, Trevor AJ (Editors).
McGraw-Hill / Lange.
3. Robertson D, Biaggioni I (2012): Adrenoceptor Antagonists (Chapter 10). In: Basic
and Clinical Pharmacology. 12e. Katzung BG, Masters SB, Trevor AJ (Editors).
4. rxlist.com (Inderal )
5. Stoschitzky K et al (1999): Influence of beta-blockers on melatonin release. Eur j
Clin Pharmacol 55(2):111-115.
Keywords
Metoprolol
Trade Names: generic, Lopressor, Toprol-XL

Drug Class: Beta-1 Selective Receptor blocker.
o a 1 selective (cardioselective) adrenoceptor blocking agent.
This preferential effect is not absolute, however, and at higher plasma
concentrations, metoprolol also inhibits 2-adrenoreceptors, chiefly located in
the bronchial and vascular musculature.
o Metoprolol has no intrinsic sympathomimetic activity, and membrane-stabilizing
activity is detectable only at plasma concentrations much greater than required for
beta-blockade.
Indications:
o Hypertension
o Post-MI
o Angina Pectoris
o CHF (see Propranolol)
Contraindications:
o Sinus bradycardia
o Heart block greater than first degree
o Cardiogenic shock & overt cardiac failure
Pharmacokinetics:
o Oral and oral sustained-release formulations are available
Side Effects:
o Fatigue
o Dizziness
o Depression
o Bradycardia
o For more information on beta-blocker CNS side effects (see propranolol).
Black Box Warning: SUDDEN DISCONTINUATION IN PATIENTS WITH ISCHEMIC

HEART DISEASE
Following abrupt cessation of therapy with certain beta-blocking agents, an increased incidence
of angina pectoris and, in some cases, myocardial infarction have occurred. When
discontinuing chronically administered metoprolol-XL (Toprol-XL ), particularly in patients with
ischemic heart disease, the dosage should be gradually reduced over a period of 1 - 2 weeks and
the patient should be carefully monitored. If angina markedly worsens or acute coronary
insufficiency develops, metoprolol-XL administration should be reinstated promptly, at least
temporarily, and other measures appropriate for the management of unstable angina should be
taken. Warn patients against interruption or discontinuation of therapy without the physician's
advice. Because coronary artery disease is common and may be unrecognized, it may be prudent
not to discontinue metoprolol-XL therapy abruptly even in patients treated only for hypertension.

o Reserpine or calcium channel blockers (additive effect)
References:
Hume JR, Grant AO (2012): Agents used in cardiac arrhythmias (Chapter 14). In:
Basic and Clinical Pharmacology. 12e. Katzung BG, Masters SB, Trevor AJ (Editors).
Robertson D, Biaggioni I (2012): Adrenoceptor Antagonists (Chapter 10). In: Basic
rxlist.com (Toprol )
Keywords
Pindolol
Trade Names: generic, Visken

Drug Class: Nonselective Beta Adrenergic Antagonist
o a synthetic non-selective blocker with intrinsic sympathomimetic
activity (its a partial agonist) at therapeutic doses, and therefore may
produce less bradycardia at rest.
Indications:
o Hypertension
Contraindications:
o Bronchial asthma
o Overt cardiac failure
o Cardiogenic shock
o Second and third degree heart block
o Severe bradycardia.
Side Effects:
o Most adverse reactions have been mild
o reserpine (additive effect)
References:
o Robertson D, Biaggioni I (2012): Adrenoceptor Antagonists (Chapter 10). In: Basic
o rxlist.com (Visken )
Keywords
Labetalol
Trade Names: generic, Normodyne, Trandate

Drug Class: Adrenergic Receptor Blocking Agent (1, 1 & 2)
o A racemic mixture of two pairs of isomers that produces adrenergic receptor block
with both selective 1 & nonselective receptor blocking actions in a single
substance
o One isomer is a potent 1 blocker, and one is a potent nonselective blocker
o Labetalol produces a greater amount of vs. blockade at therapeutic doses
o Labetalol produces dose-related falls in blood pressure without reflex tachycardia
and without significant reduction in heart rate
Indications:
o Management of hypertension
A drug of 2nd choice for treating hypertension in pregnancy (methyldopa

is a drug of first choice, with a more well-documented safety record)
Contraindications:
o Bronchial asthma
o Overt cardiac failure
o Greater-than-first-degree heart block
o Cardiogenic shock
o Severe bradycardia
o Severe and prolonged hypotension
Side Effects:
o Dizziness,
o Nausea
o Fatigue
o Postural hypotension
Pharmacokinetics:
o Oral and parenteral formulations
o Plasma half life is 6 to 8 hours
References:
o rxlist.com (Trandate )
o
Keywords
Nebivolol
Trade Names: Bystolic

Drug Class: 1 selective blocker & vasodilator
o A racemic mixture of two pairs of isomers that produces both selective 1 block &
vasodilation.
The d-isomer is a highly selective 1 blocker (the most selective 1
blocker clinically available)
the l-isomer causes the release of nitric oxide via 3 receptormediated activation of endothelial NO production (Westfall & Westfall,
2006).
o Nebivolol lacks agonist & Na channel blocking (membrane stabilizing) actions at
therapeutically relevant concentrations.
Indications:
o Treatment of hypertension.
Contraindications:
o Patients (especially those with coronary artery disease) should avoid abrupt
discontinuation of therapy due to an increased risk of myocardial infarction &
ventricular arrhythmias.
o In general, patients with bronchospastic disease should not receive beta blockers.
Side Effects:
o Relatively few reported
Pharmacokinetics:
o Oral formulations. Plasma half life of the active d-isomer is ~12 hours.
o Metabolized by a number of routes, including CYP2D6. Metabolites contribute to
beta-blocking activity
References:
o rxlist.com (Bystolic )
Keywords
Bisoprolol
Trade Name: Zebeta

o -1 selective blocker
Pharmacokinetics:
o Long half life (Once a day dosing)
References:
o rxlist.com (Zebeta )
Keywords
Timolol
Trade Names: generic, Blocadren, Betimol, Istalol

Drug Class: Nonselective Beta Adrenergic Antagonist
o a synthetic non-selective blocker (without intrinsic sympathomimetic
activity).
Indications:
o Hypertension
o Myocardial infarction
o Migraine (prophylaxis)
Contraindications:
o Bronchial asthma
o Chronic Obstructive Pulmonary Disease (COPD)
o Second and third degree heart block
o Severe bradycardia
o Patients with risk of anaphylactic reaction (beta blockers can reduce the
effectiveness of epinephrine used to treat such reactions)- a relative contraindication
Side Effects:
o Most adverse reactions have been mild & transient
o reserpine (additive effect)
o calcium channel blockers (additive effect, avoid in patients with impaired cardiac
function)
o NSAIDs (they blunt the antihypertensive effect of beta blockers)
clonidine (beta blockers can exacerbate rebound hypertension associated with

clonidine withdrawal)
References:
o rxlist.com (Blocadren )
o
Keywords
Butoxamine
Drug Class: Beta-2 Selective Adrenergic Antagonist

o Competitive antagonist at beta-2 adrenergic receptors
Indications:
o It is used in animal and tissue experiments to characterize 2 receptor involvement
and identify -2 receptors
o NO COMMON CLINICAL USE & NOT AVAILABLE FOR PRESCRIPTION OR
CLINICAL USE
Reference:
Keywords
Other Pressors
Angiotensin II
Drug Class: Vasoactive peptide

o Exerts important actions at multiple sites in the body that include vascular smooth
muscle, adrenal cortex, kidney & brain
o Its effects are mediated by activating angiotensin receptors
o Excessive activity can result in hypertension & disorders of fluid & electrolyte balance
o Ang II is a very potent pressor agent (40 times more potent than
norepinephrine)
o Clinically its effects are blocked by Angiotensin Receptor Blockers (ARBs), or by
preventing its formation using ACE Inhibitors
Pharmacokinetics:
o Ang I is converted to Ang II by ACE (Angiotensin Coverting Enzyme), a
dipeptidyl carboxypeptidase
o The plasma half life of Ang II is only 15-60 seconds
References:
o Hilal-Dandan R (2011): Renin and angiotensin (Chapter 30). In: Goodman and
Gilman's Pharmacological Basis of Therapeutics. 12e. Brunton LL, Lazo JS, Parker KL
(Editors). McGraw-Hill.
o Reid IA (2012): Vasoactive peptides (Chapter 17). In: Basic and Clinical
Pharmacology. 12e. Katzung BG, Masters SB, Trevor AJ (Editors). McGraw-Hill.

All ANS Drugs

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All ANS Drugs

Trade Name: Miochol-E

Trade Name: Levophed

Trade Name: generic, Adrenalin, Epipen

3. treatment and prophylaxis of cardiac arrest and attacks of transitory

Trade Names: generic, intropin

At HIGH DOSES dopamine activates receptors leading to

Trade Names: generic, Salagen, Isopto Carpine

Sjgrens syndrome, an autoimmune disorder where immune cells attack and

Trade Names: generic, Urecholine

Trade Names: Nicotrol Inhaler

Carbamate Cholinesterase Inhibitors

Trade Names: generic

Physostigmine should not be used in the presence of asthma, gangrene, diabetes,

Trade Names: generic, Prostigmin

Patients with known hypersensitivity to the drug

Trade Names: Mestinon, Regonol

Pyridostigmine pretreatment does not confer an advantage against

Quaternary Alcohol Cholinesterase

Trade Names: generic, Enlon Plus, Tensilon

Trade Name: Phospholine Iodide

Symptoms within seconds to hours of exposure:

Supportive measures such as assisted ventilation, diazepam for convulsions,

Drug Class: Organophosphate Chemical Warfare Agent classified as a Nerve Agent

Hurst CG, Newmark J, Romano JA Jr (2012): Chemical Bioterrorism (Chapter 222).

Drug Class: Chemical Warfare Agent classified as a Nerve Agent

Trade Names: generic, Protopam

Organophosphate aging and the effect of pralidoxime to regenerate

diazinon, malathion, mevinphos, parathion) or in chemical warfare (e.g. the nerve

Trade Name: generic, Atropen

Trade Names: generic, Transderm Scop

Trade Name: Atrovent

The half-life of elimination is about 1.6 hours after intravenous administration.

Trade Name: Robinul

Trade Name: Arfonad

Drug Class: Short acting, nondepolarizing ganglionic blocker

d-Tubocurarine (Prototype Nondepolarizing

Trade Name: generic

3. At higher concentrations they can also produce a more intense motor

Other Nondepolarizing Neuromuscular Blockers

a rapid onset of action (to allow rapid intubation)

Tubocurarine - the original nondepolarizing relaxant has:

relatively slow onset of action (4-6 mins)

Pancuronium: virtually no histamine release, but blocks muscarinic receptors. Similar

Nomenclature Heads Up:

Steroid derivatives (pancuronium, pipercuronium, rocuronium, etc) end in curonium

Depolarizing Neuromuscular Blocker /

Trade Name: Anectine

but insensitive to ACh (due to receptor desensitization). This is referred to as

Drugs Effecting the Sympathetic Nervous

Trade Name: generic (Aldomet )

Trade Name: generic

Reserpine is the active ingredient of a herbal tranquillizer from Rauwolfia serpentina

Drug Class: False neurotransmitter.

Trade Name: generic

Trade Name: generic

Trade Name: Catapres, Catapre-TTS, Duraclon

Trade Names: generic, Neo-Synephrine

Trade Name: generic, Isuprel

Trade Name: generic

Biaggioni I, Robertson D (2012): Adrenoceptor Agonists & Sympathomimetic Drugs

Trade Name: Ventolin, Combivent, Proventil

Trade Names Brethine, Bricanyl

Indirectly Acting Sympathomimetics