Dr. Samir Matloub
Drugs Acting On The Cholinergic System And The Neuromuscular
Objectives and intended learning outcomes:
The student should be able to
List the locations and types of acetylcholine receptors in the major organ systems .
Describe the steps in the synthesis, storage,release and fate of acetylcholine.
Classify cholinomimetics and describe their actions, uses and adverse
Classify different muscarinic antagonists and describe their actions, uses, adverse
effects and contraindications.
Describe the effects of nicotine and the ganglion-blocking drugs.
Classify neuromuscular blocking drugs, describe their mechanisms of action, report their clinical
applications, state their adverse effects and interpret their interactions.
The autonomic nervous system (ANS) has two parts: the sympathetic and the
Now consider the following about the ANS:
1-Spinal roots of origin:
The parasympathetic fibers originate from the 3rd , 7th , 9th & 10th cranial n. and from
S2-S4 segments of the spinal cord , while the sympathetic preganglionic fibers originate
in the thoracic T1-T12 & Lumber L1-L5.
2-Location of the ganglia:
In the PANS ( parasympathetic ANS ) the ganglia are close to the innervated organ
(ie.the preganglionic fiber is long and the postganglionic fiber is short ) the opposite is
true for SANS (sympathetic ANS) because most of the sympathetic ganglia are located in
the paravertebral chains that lie along the spinal column.
3- Innervations of organs:
a- the motor efferent portion of the PANS is one of the motor pathways for
transmission of information from CNS to the effector tissues (smooth m., cardiac m.,
b- uninervated receptors: some receptors that respond to autonomic transmitters and
drugs receive no innervation e.g. some muscarinic receptors on the endothelium of
blood vessels & some presynaptic receptors.
a. At the preganglionic synapse of the SANS & PANS the mediator is Ach.
b. At the postganglionic synapse the neurotransmitter in the PANS is Ach
while in the SANS it is norepinephrine (noradrenalin) with exception of the
thermoregulatory sweat gland (Acrine sweat gland) & some blood vessels to skeletal m.
where the mediator is Ach.
Diagram comparing some features of PANS & SANS with the somatic motor
The synthesis, storage, release and termination of action of Ach:
Ach is synthesized from acetyl co A and choline by the enzyme choline acetyl
transferase . the rate limiting step is probably the transport of choline into the nerve
terminal. This step is blocked by hemicholinium.
Ach is actively transported into the vesicles for storage. This process is inhibited by
This occurs when an action potential propagated by the action of the voltage sensitive
Na channels arrives at the nerve ending.
The release of Ach requires entry of Ca ions (through Ca voltage gated channels which
become opened) and triggering interaction between several proteins associated with the
vesicle and nerve ending membrane (synaptobrevin, snap and others)
The interaction results in the fusion of the vesicular membrane and nerve ending
membrane and release of their contents into the synaptic space.
Botuloinum toxin blocks the release of Ach .
While (by contrast) black widow spider venom causes the release of all Ach stored in
Binding to receptor:
Released Ach diffuses cross the synaptic space & bind either to postsynaptic receptor on
the target cells or to presynaptic receptor in the membrane of the neuron that released the
Termination of the action of Ach:
It is terminated in the synapse by metabolism of Ach to acetate & choline by the enzyme
acetylcholine esterase. Inhibition of those enzymes is important in the therapeutic effect
of many drugs.
Recycling of choline:
Choline is captured by Na coupled uptake system that transports the molecules back into
the neuron where it is acetylated and stored until released by a subsequent action
Cholinergic receptors (cholinoceptors):
These are subdivided into muscarinic & nicotinic receptors.
Muscarinic receptors (MRs):
These receptors are G coupled protein receptors.
Respond to muscarine as well as Ach.
The effects of activation of these receptors resemble those of postganglionic PANS
Muuscarinic receptors are located primarily on autonomic effector cells including:
heart, vascular endothelium, smooth m., presynaptic nerve terminal and exocrine
Types: M1,M2,M3,M4,M5 but the first three types are the most important.
Nicotinic receptors (NRs):
These are ion cannel receptors.
Respond to nicotine (another Ach mimic) but not to muscarine.
There are two major subtypes of nicotinic receptors: (Nn) located in the ganglia and
(Nm) located at the neuromuscular end plate of skeletal m.
Nicotinic receptors are also found in the adrenal medulla and CNS
R Location Post R. Mechanism
M1 Nerve ending Increase IP3, DAG cascade
M2 Heart , some nerve endings Decrease CAMP, activate K channels
M3 Effector cells: smooth m.,glands,endoth. Increase IP3,DAG cascade
Nn ANS ganglia Na/K depolarizing current (evokes AP)
Nm N-M junction Na/K depolarizing current
Mechanisms of Ach signal transduction(post receptor mechanisms)
Several mechanisms have been defined for muscarinic receptors:
1- The mechanism for M1 & M3 receptors:
When M1 & M3 are activated (1) they undergo conformational change & (2) interact with
a G protein which in turn (3) activates phospholipase C (a membrane bound enzyme)
leading to (4) release of second messengers DAG (DiAcyl Glecerol) and IP3 (inositol
DAG modulates the action of protein kinase C, an enzyme important in secretion while
IP3 evokes the release of Ca from intracellular storage sites which results in contraction.
2- The mechanisms for M2 receptors :
a- Couples M2 to adenylyl cyclase through an inhibitory G protein which leads to
decrease cyclic AMP production.
b- Couples M2 receptor directly to K channel in the heart and elsewhere, muscarinic
agonists facilitate the opening of these channels.
The receptor is located on the channel protein that is selective to Na & K. When the
receptor is activated the channel opens and depolarization of the cell occurs (EPSP) as a
direct result of the influx of Na. Those receptors are present on the ganglionic cells (of
both SANS & PANS) & the neuromuscular junction.
cholinergic drugs are of two types:
1-Direct acting agonists: acts directly on cholinoceptors.
2- indirect acting agonists (anticholinesterase):acts by inhibiting the action
of cholinesterase accumulation of Ach in the synaptic space
Direct acting cholinomimetic agonists:
These drugs mimic the action of Ach by binding directly to cholinoceptors.
Those agents are either:
1- Choline esters e.g. Ach, Methacoline, Carbacol and Bethanecol.
2- Naturally occurring alkaloids e.g. Muscarine , pilocorpine and Nicotine.
These drugs differ in their spectrum of action to muscarinic or nicotinic stimulation, e.g.
pilocarpine & Bethanecol preferentially bind to MRs.,however direct acting drugs (as a
group) show little specify in their action.
Effects of direct acting cholinoceptors agonists
(Only the direct effects are indicated, hemostatic responses to these direct actions may
CNS complex stimulatory effects e.g. nicotine (elevation of mood)
Sphincter m. miosis (constriction of the pupil)
Ciliary m. contraction (accommodation) to near vision
SA node heart rate (-ve chronotropy)
AV node conduction velocity (-ve chronotrophy) , R.P (refractory period)
Atria contractile strength (-ve intropy) , R.P
Ventricles small in contractile strength
Blood vessels dilation via EDRF (endothelium derived relaxation factor) (NO)
Sphincters relaxation via ENS (enteric nervous system)
trigon & sphinctor relaxation
Skeletal m, (1) activation of N-M end plate
(2) contraction of m.
Glands secretion of thermoregulatory sweat, lacrimal, bronchial, gastric and
Vasodilatation and decreased blood pressure is not evoked by PANS discharge....
-Because it is mediated by the action of uninervated muscarinic receptors found in
blood vessels which are stimulated by directly acting muscarinics (muscarinic
agonists),normally theses receptors have no function because Ach is never released
into the blood in significant quantities , stimulation of these receptors leads to the
release of NO (EDRF) which causes the vasodilatation.
Decreased blood pressure evokes a baroceptor reflex resulting in a strong sympathetic
discharge to the heart, thus the result may be tachycardia rather than bradycardia.
Another effect seen with directly acting drugs but not with PANS stimulation is
thermoregulatory sweating, this is a sympathetic-cholinergic effect.
We can predict the major clinical application of muscarinics from a consideration of
organs and diseases that benefit from an increase in cholinergic activity.
Acetylcholine is quaternary Ammonium ester that is rapidly hydrolysed by
acetylcholine esterase & plasma cholinesterase (pseudo cholinesterase); Ach
therapeutically is of no importance. Why?
Because of: (1) Its multiplicity of actions and
(2) Its rapid inactivation by cholinesterase (5-30 sec.).
Structurally, it is related to Ach but it is resistant to hydrolysis by ChE (cholinesterase)
although it can be inactivated by other esterases.
It has strong muscarinic activity but no nicotinic action.
It is orally active,its duration of action is 30m – 2hrs.
Its action is mainly on the smooth m. of the GIT and bladder; therefore, it is used for
post operative & neurogenic ileus.
Has both muscarinic & nicotinic actions
It is poor substance for ChE.
It causes the release of epinephrine from the adrenal medulla by its nicotinic action.
Duration of action is one hour.
It is used topically as a miotic agent & to decrease IOP (intraocular pressure).
It is an alkaloid & is stable to hydrolysis by ChE.
It exhibits muscarinic activity.
Duration of action is 30m – 2 hrs.
It is primarily used in ophthalmology & it is the drug of choice in the emergency
lowering the IOP both in narrow angle and wide angle glaucoma.
Pilocapine is extremely effective in the opening of trabecular meshwork around
schlemns canal causing an immediate drop of IOP as a result of increased drainage of
Pilocapine can enter the brain and can cause CNS disturbances.
The signs and symptoms of over dosage are readily predicted from the general
pharmacology of Ach
Toxicity includes CNS stimulation, miosis, spasm of accommodation,
bronchoconstriction, GIT and genitourinary smooth m. activity, secretion
activity of (sweat gland, airways and GIT) and vasodilatation.
Transient bradychardia followed by reflex tachycardia if the drug is administrated I.V.
Indirect acting agonists (Anticholinesterases):
Drugs that inhibit the activity of cholinesterase indirectly provide a cholinergic action
by prolonging the life time of Ach, produced endogenously at the cholinergic nerve
These drugs therefore lead to the accumulation of Ach in the synaptic space and can
produce a response at all cholinoceptors in the body, including both muscarinic and
nicotinic receptors of the ANS as well as the neuromuscular junction and the brain.
Anticholinesterase can be subdivided into reversible AchE and irreversible AchE.
Are carbonic acid esters "carbamates"
Neostigmine is prototype.
2- Irreversible agents:
Are phosphoric acid esters "organophosphates"
Isoflurophate and echothiophate are prototypes.
A third class which has only one number:
Edrophonium : is an alcohol (not an ester) which is reversible with a very short
duration of action.
1- Reversible Anti ChE:
The carbamate residue is released by ChE over a period of 2-8 hours.
Physostigmine: is an alkaloid , it’s a tertiary amine (can enter and simulate the
1- Because it increases intestinal and bladder motility thus it is used in case of atony
of bladder and paralytic ileus.
2- It is also used to treat over dose of drugs with anticholinergic action. Such as
Atropine, Phenothiazine, and TCA (tricyclic antidepressants)
3- Intraocular pressure (IOP) thus it is useful in glaucoma but pilocarpine is
CNS: may lead to convulsions. In over dose, bradychardia and neuromuscular (N-M)
paralysis may also occur.
Neostigmine: is a synthetic compound (doesn’t enter the CNS), its effect on the
skeletal muscles is more than physostigmine because it also has direct action on
skeletal m. cholinergic receptors(nicotinic receptors of the N-M junction).
1- Post operative and neurogenic ileus and urinary retention.
2- Antidote for tubocurarine and other competitive N-M blockers.
3- Symptomatic treatment of myasthenia gravis (weakness in the muscles).
Pyridostigmine: it’s duration of action is (3-6 hours) which is longer than
Neostigmine (2-4 hours).
Used in chronic management of myasthenia gravis.
Edrophonium: short duration of action (10-20 min).
1- Used in diagnosis of mysthenia gravis and to differentiate mysthenic crisis
from cholinergic crisis.
2- Used as antidote to curare like drugs.
2- Irreversible Anti ChE:
A number of synthetic organophosphates have the capacity to bind covalently to ChE
forming an extremely stable phosphate complex with the enzyme.
The end result is increased Ach at all sites where it is released. Many of these drugs are
extremely toxic and were developed by the military as nerve gas agents, related comp.
such as parathion are employed as insecticides.
4 organophosphates are used in medicine these are isoflurophate (DFP) and
echothiophate (are used as antiglaucoma agents). Malathion as a *scabicide and
metrifonate as *anti helimenthic agent.
Toxicity of Irreversible Anti ChE:
This usually occurs because of accidental exposure to toxic amount of pesticides, the
most toxic of these drugs (e.g. parathion) are rapidly fetal if the exposure is not
immediately recognized and treated.
Signs and symptoms of poisoning: include general cholinergic stimulation
(muscarinic and nicotinic), paralysis of motor function "causing breathing difficulty " ,
CNS stimulation leading to convulsions followed by respiratory and cardiovascular
The spectrum of toxicity can be remembered with the aid of the mnemonic
M: miosis (contraction of pupil)
E: excitation of skeletal muscles and CNS followed by depression
S: salivation and sweating
Treatment of toxicity:
1- Contaminated clothing should be removed and the skin washed. Gastric lavage may
be needed if many of the substances have been ingested. Mechanical ventilation may
2- Atropine is the main stay of treatment; 2 mg is given IV or IM as soon as possible
and repeated every 15-60 minutes. A 100 mg of Atropine may be required for a
poisoned patient. Atropine antagonizes the muscarinic actions but has no effect on
the nicotinic signs of toxicity.
3- Enzyme reactivation (enzyme regeneration) by using enzyme regenerators,
compounds such as pralidoxime are used, which may also reverse the nicotinic
signs if used early on "before aging occurs"
Aging: is a further chemical change in the enzyme which renders regenerator drugs
unable to remove the inhibitor (organophosphates phosphorylate the active site of the
enzyme cholinesterase, and following this covalent modification the phosphorylated
enzyme undergoes a further chemical change (losses an alkyl group) which is called
aging that makes it impossible for pralidoxine to break the bond between the remaining
organophosphates and the enzyme.)
Is an oxime compound. The oxime group has an extremely high affinity for the
phosphate atom in the organophosphates insecticides because the affinity of the oxime
group for the phosphorus exceeds that of the enzymes active site. This agent is therefore
able to bind the inhibitor and displace (regenerate) the enzyme if aging has not
occurred. Pralidoxine is given in a dose of 1 gm every 4 hours IM or by slow IV
best results are obtained if it is given is within the first12 hours of poisoning.
Muscle power may improve within 30 min.
Anti Muscarinics Anti Nicotinics
M1 selective Nonselective Ganglion blockers N-M blockers
These agents (e.g. Atropine & Scopolamine) act as competitive
"surmountable" pharmacological antagonists.
They block muscarinic receptors causing inhibition of all muscarinic
functions and their blocking effects are overcome by increasing the
concentration of Ach or by other muscarinic agonists.
These drugs also block the few exceptional sympathetic neurons that are
cholinergic "e.g. sweat gland" .
These drugs have little or no effect on the autonomic ganglia or the N-M
Most of these drugs are nonselective for muscarinic receptors except for
pirenzepine and telenzepine which are M1 selective (used in treatment
of peptic ulcers).
The action of muscarinic blockers (e.g. atropine) is mostly predictable
effects derived from cholinoceptor blockade.
Effects of muscarinic blocking drugs:
Organs Effect Mechanism
Sedation, anti motion sickness
Block of MRs, unknown
CNS action, anti parkinsonian action,
Mydriasis, cycloplegia (paralysis
Eye Block of M3 Rs
Bronchodilatation esp. if
Bronchi Block of M3 Rs
GIT Relaxation, slowed peristalsis. Block of M1,M3 Rs
Genito- Relaxation of the bladder wall,
Block of M3 Rs
urinary tract Urinary retention.
Initial bradycardia, esp. at low Tachycardia from block of
doses then tachycardia. M2 R in the heart.
Block of muscarinic
vasodilatation , not manifested Block of M3 Rs on
unless a muscarinic agonist is endothelium of B.Vs
Marked reduction of salivation,
Block of M1, M3
Glands lacrimation,sweating, less
reduction of gastric secretion.
Skeletal m. none
CNS effects are less predictable. CVS effects at therapeutic doses include an
initial slowing of the heart rate caused by a central mechanism (medullary
stimulation of the cardiac inhibitory centre) or more likely by presynaptic
vagal effects (blocking the presynaptic M1R on vagal post ganglionic fibers
that normally limit Ach release in the SA node).this slowing is followed by
tachycardia and decrease AV conduction time as it would be predicted from
peripheral vagal blockade (blocking of M2 receptors in the heart).
The effect on the blood vessels include blockade of the endothelial
muscarinic receptors that mediate vasodilatation and also vasodilatation
produced by sympathetic cholinergic nerve stimulation to the skeletal muscle
vascular bed. However there is a little effect on blood pressure of normal
persons. At toxic doses atropine may cause cutaneous vasodilatation in the
upper part of the body, the mechanism is unknown.
Clinical uses of muscarinic antagonists:
Note: topical activity (the ability to enter the eye after conjuctival
administration) and similar ability to cross lipid barrier (e.g. BBB) is
important in determining the usefulness of several antimuscarinics often used
in ophthalmology and in Parkinsonism. In contrast the antimuscarinic drugs
used for their antisecretory or antispasmodic actions in the gut or in the
bronchi are often selected for minimum CNS activity (these drugs may
incorporate quaternary amine group to limit penetration to the CNS).
- Motion sickness: scopolamine is the standard therapy in motion
- Parkinsonism: Benztropine, biperidine, trihexphenidyl (these drugs
are mainly effective to control tremors).
Benztropine is sometimes used to treat acute dystonias caused by
2- Eye: are used to dilate the pupil (mydriasis) and to paralyze
Drugs used to this purpose include (in descending order of duration of
Atropine < 72 hours, homatropine (24 hrs.), cyclopentolate (2-12 hrs.),
tropicamide (0.5-4 hrs.).
3-Bronchi: Parentral atropine has been used to reduce airway secretion
during surgery. Ipratropium a quaternary agent is used by inhalation to
reduce bronchoconstriction in asthma and COPD (chronic obstructive
pulmonary disease). This drug has very few antimuscarinic effects outside the
lung because it is rapidly metabolized and poorly absorbed. it is less effective
than B2 agonists in this regard.
4- CVS: Parentral atropine and similar antimuscarinics are used to H.R
in cases of bradychardia due to depression of the SA node or the AV node
function (e.g. after myocardial infarction (MI) and in persons with
hyperactive carotid sinus reflexes).
5- Gut: Atropine, methscopolamine and propantheline were used in the
past in acid peptic disease to reduce acid secretion (volume, amount of acid
and pepsin and mucin are all reduced but large doses are required).
These drugs are less effective than the H2 antagonist (e.g. cimitidine)
and produce frequent side effects.
Pirenzepine and telenzepine are M1, selective antagonist, may be more
useful in peptic ulcer (M1 receptors are present on the ECL cells and not
on parietal cells which possess M3R.)
Muscarinic antagonist e.g. glycopyrolate, dicyclomine, hyoscin butyl
bromide and methscopolamine can be used to reduce cramping
(antispasmodic) and hepermotility in transient diarrheas but
diphenoxylate (an opioid) is more effective.
6- Urinary system: Oxybutynin, glycopyrolate, dicyclomine are used
in the treatment of spasm and urgency induced by mild inflammation e.g.
(cystitis), surgery and neurological conditions but can precipitate urinary
retention in elderly men with benign prostatic hyperplasia (Bph).
Tolterodine (is an M3 selective antimuscarinic) is used in adult with
7- Other uses: As an antidote for cholinergic agonists atropine is used in
the treatment of organophosphorus poisoning and some types of mushroom
poisoning.Atropine because of its ability to enter CNS is used to block the
effect of excess Ach resulting from inhibition of ChE by drugs such as
Is the protypical non selective muscarinic blocker , It is an alkaloid found
in atropa belladonna. It is a tertiary amine (lipid soluble and crosses to the
CNS). It is eliminated partly by metabolism and by renal excretion t ½ is 2
hrs., Duration of action is 4-8 hrs except in the eye where the effect lasts for
72 hrs. or longer. the antidote in atropine poisoning is physostigmine.
Is another belladonna alkaloid similar to atropine but has a longer duration
of action and greater action on the CNS. It produces sedation. Its use is limited
for the prevention and treatment of motion sickness.
Adverse effects and toxicity:
Most of the adverse effects are predictable antimuscarinic effects, although
there are some unpredictable actions.
Predictable include: Dry mouth, blurred vision, tachycardia, constipation,
hyperthermia due to blockage of thermo-regulatory sweating also called
atropine fever (this occurs esp. in infants which may be dangerous.)
Atropine toxicity is described as feeling as dry as a bone because
sweating, salivation and lacrimation are reduced or stopped. In the elderly
atropine may cause acute angle-closure glaucoma and urinary retention esp.
in patients with Bph (benign prostatic hyperplasia)
1- CNS toxicity which includes: sedation, amnesia and delirium or
hallucination (described as mad as a hatter) convulsions may also occur.
2- CVS which include: intra ventricular conduction block and cutaneous
vasodilatation of the vessels of head, neck, arms and trunk (atropine flush)
which is described as red as beet, which may be diagnostic.
These drugs should be cautiously used in infants (hyperthermia) these
drugs are relatively CI in patients with glaucoma and in men with Bph.
A-Ganglionic blocking drugs:
These agents act specifically on nicotinic receptors by blocking the ion
channels in the ganglia both sympathetic and parasympathetic. Thus they
block the entire output of the ANS at the nicotinic receptors. They have no
effect on N-M junction .they were the 1st successful agents in the treatment of
hypertension. However because of their adverse effect, they are rarely used
nowadays. Examples of these drugs are hexamothanium, mecamylamine
Nicotine: present in tobacco smoke and is used in the form of chewing
gum or transdermal patches by smokers to get rid of smoking and is still used
in some insecticides. Depending on the dose nicotine 1st stimulate the ganglia
which is followed by blockade. The stimulatory effects are complex which
include CNS stimulation Bp, HR (due to increase transmitter release from
adrenergic nerve terminals and adrenal medulla), peristalsis and secretion
and ADH release.
At higher doses Bp because of ganglionic blockade and the activity of
the smooth muscles and secretion is blocked.
B- Neuromuscular blocking drugs:
These neuromuscular blockers are structural analogues of Ach they are
1- A non- depolarizing type: (act as antagonists) e.g. tubocurarine.
2- A depolarizing type (act as agonists) e.g. succinylcholine.
N-M blockers are clinically useful during surgery to produce complete
muscle relaxation without the need to employ high anesthetic doses to
achieve a comparable muscle relaxation.
Non-depolarizing type (competitive N-M blockers):
(tubocurarine, pancuronium, gallamine, rocuronium, atracurium,
mivacurium, vecuronium, doxacurium).
All of these drugs are given parentraly. They differ in their onset and duration
of action (Rocuronium has the fastest onset of action), whether they are
metabolized by plasma choline esterase (e.g. mevacurrium) or eliminated in
bile (e.g.vecuronium) or by the kidney (e.g. doxacurium, pancuronium,
tubocurarine) or eliminated by an independent mechanism (e.g. atracurium)
which involves spontaneous breakdown called (hoffmann elimination).
Also these drugs differ in their autonomic effects and their ability to release
histamine e.g. tubocurarine blocks the ganglia and is the most likely of N-M
blockers to cause histamine release. Histamine release also occurs to a less
extent with atracurium and mivacurium , on the other hand pancuronium
and gallamine block the cardiac muscarinic receptors causing tachycardia.
Mechanism of action of non-depolarizing agents:
These drugs compete with Ach and produce a competitive block at the end
plate nicotinic receptors and thus prevent the depolarization of the muscle cell
membrane causing flaccid paralysis.
The action of these drugs can be overcome by the concentration of Ach at
the synaptic cleft e.g. by administration of ChE inhibitors (neostigmine or
edrophorium) some drugs in this group or when given in high doses may
directly act to plug (close) the ion channels of the end plate, this leads to
further weakening of N-M transmission and reduces the ability of ChE
inhibitors to reverse the action of these drugs.
small rapidly contracting muscles of the face and eye are the most
susceptible to blockage and are paralyzed first followed by the muscles of the
fingers then the limbs then neck and trunk muscles then the intercostals
muscles and lastly the diaphragm.
Therapeutic uses: these drugs are used mainly as surgical adjuvant to
anesthesia for promoting skeletal muscle relaxation and for facilitating endo-
1- Respiratory paralysis if mechanical ventelation is not provided.
2- Autonomic effect and histamine release depending on the drugs used (e.g.
Halogenated hydrocarbon anesthetics (halothane, Enflurane),
aminoglycoside antibiotics (e.g. gentamycin, tobramycin), calcium channel
blockers and some antiarrythmic drugs (e.g. quinidine) increase the effect of
N-M blockers. On the other hand ChE inhibitors antagonize their effect.
Succinylcholine (suxamethonium), decamethonium these depolarizing
agents act like Ach.on the nicotinic receptors of the motor end plate to
depolarize the junction.But unlike Ach, succinylcholine (because is not
rapidly hydrolyzed by ChE) remains attached to the receptor for a relatively
longer time providing a constant stimulation of the receptor.
Succinyl choline therefore first causes the opening of Na – channel associated
with nicotinic receptor which results in depolarization of the receptor (phase I)
this leads to a transient twitching of the muscle (fasciculation).
The continued binding of the depolarizing agent render the receptor incapable
of transmitting further impulses (desensitization) and results in flaccid
paralysis (phase II) in which the membrane repolarizes but the receptor is
desensitized to the effect of Ach.(a curare like effect). If a cholinesterase
inhibitor is given,
phase I is augmented but it may reverse phase II block.
Because of its rapid onset and short duration of action (only few minutes if
given as single dose) succinyl choline is useful for endotracheal intubation
during induction of anesthesia and may be also used during ECT (electro-
Because of its brief duration of action (due to its rapid hydrolysis by plasma
ChE) it is usually given by a continuous infusion.
Malignant hyperthermia in genetically susceptible individual when
succinyl choline is used in combination with Halothane (anesthetic),
hyperpyrexia and muscle rigidity may occur, this is treated by rapidly
cooling the body and by administration of Dantrolene which blocks the
release of Ca from sarcoplasmic reticulum of the muscle cell thus reducing
heat and decreasing muscle rigidity which is associated with hyperpyrexia.
Apnea: a genetically related deficiency of plasma ChE or the presence of
atypical form of the enzyme can lead to prolonged apnea.
Other adverse effects include: post operative muscle pain, intragastric
pressure which may promote emesis (vomiting), IOP ,
hyperkalemia(especially in patients with burns).
Succinyl choline may cause stimulation of the autonomic ganglia and cardiac
muscarinic receptor (bradycardia) and has a slight ability to release histamine.
By: Maryam Samir