Parasympatholytics+MLT+3RD SEMSTER+BAASIR UMAIR.pptx

Parasympatholytics
Baasir Umair Mphil in Pharmacology

03/31/2025 Dr. Baasir Umair 2
ANTICHOLINERGIC DRUGS
(Muscarinic receptor antagonists,
Atropinic, Parasympatholytic)
Conventionally, the term
‘anticholinergic drugs’ is restricted to
those which block actions of ACh on
autonomic effectors and in the CNS
exerted through muscarinic receptors.
Though nicotinic receptor
antagonists also block certain actions
of ACh, they are generally referred to
as ‘ganglion blockers’ and
‘neuromuscular blockers’

 Atropine, the prototype drug of this class, is highly selective for muscarinic
receptors, but some of its synthetic substitutes do possess significant nicotinic
blocking property in addition.
 The selective action of atropine can easily be demonstrated on a piece of
guinea pig ileum where ACh induced contractions are blocked without
affecting those evoked by histamine, 5-HT or other spasmogens.
 The selectivity is, however, lost at very high doses.
 All anticholinergics are competitive antagonists.

In addition, many other classes of drugs, i.e. tricyclic
antidepressants, phenothiazines, antihistamines and
disopyramide possess significant antimuscarinic
action
In addition, many other classes of
drugs, i.e. tricyclic antidepressants,
phenothiazines, antihistamines and
disopyramide possess significant
antimuscarinic action
Muscarinic antagonist

Nicotinic antagonist

ANTIMUSCARINIC AGENT
 Commonly known as anticholinergic drugs, these agents (for example, atropine and
scopolamine) block muscarinic receptors, causing inhibition of muscarinic functions.
 In addition, these drugs block the few exceptional sympathetic neurons that are
cholinergic, such as those innervating the salivary and sweat glands.
 Because they do not block nicotinic receptors, the anticholinergic drugs (more
precisely, antimuscarinic drugs) have little or no action at skeletal neuromuscular
junctions (NMJs) or autonomic ganglia.
 The anticholinergic drugs are beneficial in a variety of clinical situations.

(Atropine as prototype)
• Atropine is a tertiary amine belladonna alkaloid with a high affinity for muscarinic
receptors.
• It binds competitively and prevents ACh from binding to those sites. Atropine acts both
centrally and peripherally.
• Its general actions last about 4 hours, except when placed topically in the eye, where the
action may last for days.

(Atropine as prototype)
PHARMACOKINETIC
Atropine and hyoscine
are rapidly absorbed
from g.i.t. Applied to
eyes they freely
penetrate cornea.
Distribution
• Atropine and the other tertiary agents are widely
distributed in the body.
• Significant levels are achieved in the CNS within
30 minutes to 1 hour, and this can limit the dose
tolerated when the drug is taken for its peripheral
effects.
• In contrast, the quaternary derivatives are poorly
taken up by the brain and therefore are relatively
free—at low doses—of CNS effects.
Absorption

Metabolism and Excretion
About 50% of the dose is excreted unchanged in the urine. Most of the rest appears in
the urine as hydrolysis and conjugation product.
After administration, the elimination of atropine from the blood occurs in two
phases:
The t1/2 of the rapid phase is 2hours and that of the slow phase is approximately 13
hours.
And that of the slow phase is approximately 13 hours.
Effects on the iris
and ciliary muscle
persist for ≥ 72
hours
The drug’s effect on
parasympathetic
function declines
rapidly in all organs
except the eye.

Pharmacodynamics
Mechanism of Action
• Atropine causes reversible
(surmountable) blockade of
cholinomimetic actions at muscarinic
receptors; that is, blockade by a small
dose of atropine can be overcome by a
larger concentration of acetylcholine or
equivalent muscarinic agonist.
• Mutation experiments suggest that
aspartate in the third transmembrane
segment of the heptahelical receptor
forms an ionic bond with the nitrogen
atom of acetylcholine; this amino acid is
also required for binding of
antimuscarinic drugs.
When atropine binds to the muscarinic
receptor
it prevents actions such as the release of
inositol trisphosphate (IP3)
It causes the inhibition of adenylyl
cyclase that are caused by muscarinic
agonists

Mechanism of Action

• Classically, muscarinic antagonists were viewed as neutral compounds that
occupied the receptor and prevented agonist binding.
• Recent evidence indicates that muscarinic receptors are constitutively active, and
drugs that block the actions of acetylcholine are inverse agonists that shift the
equilibrium to the inactive state of the receptor.
• Muscarinic blocking drugs that are inverse agonists include atropine, pirenzepine,
trihexyphenidyl, AF-DX 116, 4-DAMP, and a methyl derivative of scopolamine.

• Atropine is highly selective for
muscarinic receptors.
• Its potency at nicotinic receptors is
much lower, and actions at
nonmuscarinic receptors are
generally undetectable clinicall
• Atropine does not distinguish among
the M1, M2, and M3 subgroups of
muscarinic receptors.
• In contrast, other antimuscarinic drugs
are moderately selective for one or
another of these subgroup
• Most synthetic antimuscarinic drugs
are considerably less selective than
atropine in interactions with
nonmuscarinic receptors.
• For example, some quaternary amine
antimuscarinic agents have
significant ganglion-blocking
actions, and others are potent
histamine receptor blockers

PHARMACOLOGICAL ACTIONS
1. CNS Atropine:
• It has an overall CNS stimulant action.
• However, these effects are not appreciable at low doses which produce only
peripheral effects because of restricted entry into the brain.
• Hyoscine produces central effects (depressant) even at low doses
• Atropine stimulates many medullary centres —vagal, respiratory, vasomotor.
• It depresses vestibular excitation and has antimotion sickness property.
• The site of this action is not clear—probably there is a cholinergic link in the
vestibular pathway, or it may be exerted at the cortical level

• By blocking the relative cholinergic overactivity in basal ganglia, it
suppresses tremor and rigidity of parkinsonism
Majority of the central actions are due to blockade of muscarinic receptors in
the brain, but some actions may have a different basis.
High doses cause cortical excitation, restlessness, disorientation,
hallucinations and delirium followed by respiratory depression and coma.

2. CVS
Heart
• The most prominent effect of atropine is tachycardia.
• It is due to blockade of M2 receptors on the SA node through which vagal tone
decreases HR.
• Higher the existing vagal tone— more marked is the tachycardia (maximum in
young adults, less in children and elderly).
• On i.m./s.c. injection transient initial bradycardia often occurs.
• Earlier believed to be due to stimulation of vagal centre, it is now thought to be
caused by blockade of muscarinic autoreceptors (M1) on vagal nerve endings,
thereby augmenting ACh release.
• This is suggested by the finding that selective M1 antagonist pirenzepine is
equipotent to atropine in causing bradycardia.
• Moreover, atropine substitutes which do not cross bloodbrain barrier also produce
initial bradycardia. Atropine abbreviates refractory period of A-V node and
facilitates A-V conduction, especially if it has been depressed by high vagal tone.

2. CVS
BP:
• Since cholinergic impulses are not involved in the maintenance of vascular tone,
atropine does not have any consistent or marked effect on BP.
• Tachycardia and vasomotor centre stimulation tend to raise BP, while histamine
release and direct vasodilator action (at high doses) tend to lower BP.
• Atropine blocks vasodepressor action of cholinergic agonists.

3. Eye
• The autonomic control of iris muscles and the action of mydriatics as well as miotics
is illustrated.
• Topical instillation of atropine causes mydriasis, abolition of light reflex and
cycloplegia lasting 7–10 days. This results in photophobia and blurring of near
vision.
• The ciliary muscles recover somewhat earlier than sphincter pupillae.
• The intraocular tension tends to rise, especially in narrow angle glaucoma.
• However, conventional systemic doses of atropine produce minor ocular effects.

4. Smooth muscles:
• All visceral smooth muscles that receive parasympathetic motor innervation are
relaxed by atropine (M3 blockade).
• Tone and amplitude of contractions of stomach and intestine are reduced; the
passage of chyme is slowed—constipation may occur, spasm may be relieved.
• However, peristalsis is only incompletely suppressed because it is primarily
regulated by local reflexes in the enteric plexus, and other neurotransmitters (5-HT,
enkephalin, etc.) are involved.
• Enhanced motility due to injected cholinergic drugs is more completely antagonised
than that due to vagal stimulation, because intramural neurones which are activated
by vagus utilize a number of noncholinergic transmitters as well.

• Atropine causes bronchodilatation and reduces airway resistance, especially in
COPD and asthma patients.
• Inflammatory mediators like histamine, PGs, leucotrienes and kinins which
participate in asthma increase vagal activity in addition to their direct stimulant
action on bronchial muscle and glands. Atropine attenuates their action by
antagonizing the reflex vagal component.
• Atropine has relaxant action on ureter and urinary bladder; urinary retention can
occur in older males with prostatic hypertrophy.
• However, this relaxant action can be beneficial for increasing bladder capacity
and controlling detrusor hyperreflexia in neurogenic bladder/enuresis.
• Relaxation of biliary tract is less marked and effect on uterus is minimal.

5. Glands:
• Atropine markedly decreases sweat, salivary, tracheobronchial and lacrimal
secretion (M3 blockade). Skin and eyes become dry, talking and swallowing may be
difficult.
• Atropine decreases secretion of acid, pepsin and mucus in the stomach, but the
primary action is on volume of secretion so that pH of gastric contents may not be
elevated unless diluted by food.
• Since bicarbonate secretion is also reduced, rise in pH of fasting gastric juice is only
modest.
• Relatively higher doses are needed and atropine is less efficacious than H2 blockers
in reducing acid secretion.
• Intestinal and pancreatic secretions are not significantly reduced.
• Bile production is not under cholinergic control, so not affected.

6. Body temperature:
• Rise in body temperature
occurs at higher doses.
• It is due to both inhibition of
sweating as well as
stimulation of temperature
regulating centre in the
hypothalamus.
• Children are highly
susceptible to atropine fever
7. Local anaesthetic:
• Atropine has a mild anaesthetic action
on the cornea.
• Atropine has been found to enhance
ACh (also NA) release from certain
postganglionic parasympathetic and
sympathetic nerve endings, and thus
produce paradoxical responses.
• This is due to blockade of release
inhibitory muscarinic autoreceptors
present on these nerve terminals

ADRS

• This natural anticholinergic alkaloid differs from atropine in many respects, these are
tabulated in Table.
• Scopolamine [skoe-POL-a-meen], another tertiary amine plant alkaloid, produces
peripheral effects similar to those of atropine.
• However, scopolamine has greater action on the CNS (unlike atropine, CNS effects are
observed at therapeutic doses) and a longer duration of action as compared to atropine.
Hyoscine/ Scopolamine

Scopolamine is rapidly and fully distributed into the CNS
where it has greater effects than most other antimuscarinic
drugs.
Distribution
Hyoscine is rapidly
absorbed from g.i.t.
Applied to eyes it
freely penetrate cornea.
Absorption
PHARMACOKINETIC

Actions:
• Scopolamine is one of the most effective
anti–motion sickness drugs available.
• It also has the unusual effect of blocking
short-term memory.
• In contrast to atropine, scopolamine
produces sedation, but at higher doses.
• It can produce excitement.
• Scopolamine may produce euphoria and is
susceptible to abuse.
Therapeutic uses:
• The therapeutic use of
scopolamine is limited to
prevention of motion sickness and
postoperative nausea and
vomiting.
• For motion sickness, it is
available as a topical patch that
provides effects for up to 3 days.
• [Note: As with all drugs used for
motion sickness, it is much more
effective prophylactically than for
treating motion sickness once it
occurs.

ADRS

ATROPINE SUBSTITUTES

ATROPINE SUBSTITUTES
• Many semisynthetic
derivatives of belladonna
alkaloids and a large
number of synthetic
compounds have been
introduced with the aim
of producing more
selective action on certain
functions.
• Most of these differ only
marginally from the
natural alkaloids, but
some recent ones appear
promising
Quaternary compounds
These have certain common features:
• Incomplete oral absorption.
• Poor penetration in brain and eye; central
and ocular effects are not seen after
parenteral/ oral administration.
• Elimination is generally slower; majority are
longer acting than atropine.
• Have higher nicotinic blocking property.
Some ganglionic blockade may occur at
clinical doses → postural hypotension,
impotence are additional side effects.
• At high doses some degree of
neuromuscular blockade may also occur

1. Hyoscine butyl bromide:
20–40 mg oral, i.m., s.c., i.v.; less potent and
longer acting than atropine; used for esophageal
and gastrointestinal spastic conditions.
BUSCOPAN 10 mg tab., 20 mg/ml amp.
2.Atropine
methonitrate:
2.5–10 mg oral,
i.m.; for abdominal
colics and
hyperacidity.

3. Ipratropium bromide
Dose:
40–80 µg by inhalation.
• It has a gradual onset and late
peak (at 40–60 min) of
bronchodilator effect in
comparison to inhaled
sympathomimetics.
• Thus, it is more suitable for
regular prophylactic use rather
than for rapid symptomatic relief
during an attack
Another desirable feature is
that in contrast to atropine,
it does not depress
mucociliary clearance by
bronchial epithel Action lasts 4–6 hours.

Action:
It acts on receptors located
mainly in the larger central
airways (contrast
sympathomimetics whose
primary site of action is
peripheral bronchioles
• The parasympathetic tone is the
major reversible factor in chronic
obstructive pulmonary disease
(COPD).
• Therefore, ipratropium is more
effective in COPD than in
bronchial asthma.
Uses:
Side Effect:
Transient local side effects like
dryness of mouth, scratching
sensation in trachea, cough, bad
taste and nervousness are reported
in 20–30% patients, but systemic
effects are rare because of poor
absorption from the lungs and g.i.t.
(major fraction of any inhaled drug
is swallowed)
Dose:
20 µg and 40 µg/puff metered dose inhaler,
2 puffs 3–4 times daily; 250 µg/ml
respirator soln., 0.4–2 ml nebulized in
conjunction with a β2 agonist 2–4 times
daily
Also
used
to
control
rhinorrhoea
in
perennial
rhinitis
and
common
cold;

4. Tiotropium bromide
A newer congener of
ipratropium bromide
which binds very
tightly to bronchial
M1/M3 muscarinic
receptors producing
long lasting
bronchodilatation
Binding to M2 receptors is less tight
confering relative M1/M3 selectivity (less
likely to enhance ACh release from vagal
nerve endings in lungs due to M2 receptor
blockade).
Like ipratropium, it is not absorbed from
respiratory and g.i. mucosa and has exhibited
high bronchial selectivity of action.
Dose: 18 μg

5.Propantheline:
• Dose: 15–30 mg oral
• it was a popular anticholinergic
drug used for peptic ulcer and
gastritis.
• It has some ganglion blocking
activity as well and is claimed to
reduce gastric secretion at doses
which produce only mild side
effects. Gastric emptying is
delayed and action lasts for 6–8
hours.
• Use has declined due to
availability of H2 blockers and
proton pump inhibitors.
• PROBANTHINE 15 mg tab.
6. Oxyphenonium :
5–10 mg (children 3–5 mg) oral;
similar to propantheline,
recommended for peptic ulcer and
gastrointestinal hypermotility.
ANTRENYL 5, 10 mg tab
7. Clidinium 2.5–5 mg oral;
This antisecretory antispasmodic has
been used in combination with
benzodiazepines for nervous dyspepsia,
gastritis, irritable bowel syndrome,
colic, peptic ulcer, etc

8.Pipenzolate methyl
bromide 5–10 mg (children
2–3 mg) oral;
• It has been promoted
especially for flatulent
dyspepsia, infantile colics
and abdominal cramps.
9. Isopropamide 5 mg oral;
indicated in hyperacidity, nervous
dyspepsia, irritable bowel and
other gastrointestinal problems,
specially when associated with
emotional/mental disorders
10.Glycopyrrolate:
0.1–0.3 mg i.m. (5–10
μg/kg), potent and rapidly
acting antimuscarinic
lacking central effects.
Almost exclusively used for
preanaesthetic medication
and during anaesthesia

Tertiary amines
1.Dicyclomine:
(20 mg oral/i.m., children 5–10 mg/kg)
• It has direct smooth muscle relaxant action in addition to weak anticholinergic.
• It exerts antispasmodic action at doses which produce few atropinic side effects.
• However, infants have exhibited atropinic toxicity symptoms and it is not
recommended below 6 months of age.
• It also has antiemetic property: has been used in morning sickness and motion
sickness.
• Dysmenorrhoea and irritable bowel are other indications.

2. Valethamate:
The primary indication of this
anticholinergic-smooth muscle
relaxant is to hasten dilatation of
cervix when the same is delayed
during labour, and as visceral
antispasmodic, urinary, biliary,
intestinal colic.
Dose: 8 mg i.m., 10 mg oral
repeated as required.
3. Pirenzepine:
(100–150 mg/day oral)
• It selectively blocks M1 muscarinic
receptors and inhibits gastric
secretion without producing typical
atropinic side effects (these are due to
blockade of M2 and M3 receptors).
• The more likely site of action of
pirenzepine in stomach is intramural
plexuses and ganglionic cells rather
than the parietal cells themselves.
• It is nearly equally effective as
cimetidine in relieving peptic ulcer
pain and promoting ulcer healing, but
has been overshadowed by H2
blockers and proton pump inhibitors.
Tertiary amines

Vasicoselective drugs
1. Oxybutynin:
• This newer antimuscarinic has high affinity for receptors in urinary bladder and
salivary glands alongwith additional smooth muscle relaxant and local anaesthetic
properties.
• It is relatively selective for M1/M3 subtypes with less action on the M2 subtype.
• Because of vasicoselective action, it is used for detrusor instability resulting in
urinary frequency and urge incontinence.
• Beneficial effects: have been demonstrated in post-prostatectomy vasical spasm,
neurogenic bladder, spina bifida and nocturnal enuresis.
• Anticholinergic side effects:are common after oral dosing, but intravasical
instillation increases bladder capacity with few side effects.
• Oxybutynin is metabolized by CYP3A4; its dose should be reduced in patients
being treated with inhibitors of this isoenzyme.
• Dose: 5 mg BD/TDS oral; children above 5 yr 2.5 mg BD

2. Tolterodine:
• This relatively M3 selective muscarinic antagonist has preferential action on
urinary bladder; less likely to cause dryness of mouth and other anticholinergic side
effects.
• It is indicated in overactive bladder with urinary frequency and urgency.
• Since it is metabolized by CYP3A4, dose should be halved in patients receiving
CYP3A4 inhibitors (erythromycin, ketoconazole, etc.)
• Dose: 1–2 mg BD or 2–4 mg OD of sustained release tab. oral.
Darifenacin and Solifenacin are other relatively M3 subtype selective
antimuscarinics useful in bladder disorders.

3.Flavoxate has properties similar to
oxybutynin and is indicated in urinary
frequency, urgency and dysuria associated with
lower urinary tract infection
Drotaverine:
It is a novel non-anticholinergic smooth muscle antispasmodic
which acts by inhibiting phosphodiesterase-4 (PDE-4) selective for
smooth muscle. Elevation of intracellular cAMP/cGMP attends
smooth muscle relaxation. Changes in membrane ionic fluxes and
membrane potential have also been shown. It has been used orally
as well as parenterally in intestinal, biliary and renal colics,
irritable bowel syndrome, uterine spasms, etc. without
anticholinergic side effects. Adverse effects reported are headache,
dizziness, constipation and flushing. Fall in BP can occur on i.v.
injection. Dose: 40–80 mg TDS

Mydriatics
• Atropine is a potent mydriatic but its slow and long-lasting action is undesirable for
refraction testing.
• Though the pupil dilates in 30–40 min, cycloplegia takes 1–3 hours, and the subject
is visually handicapped for about a week.
• The substitutes attempt to overcome these difficulties.
1. Homatropine:
• It is 10 times less potent than atropine.
• Instilled in the eye.
• It acts in 45–60 min, mydriasis lasts 1–3 days while accommodation recovers in
1–2 days.
• It often produces unsatisfactory cycloplegia in children who have high ciliary
muscle tone.

2. Cyclopentolate:
• It is potent and rapidly acting; mydriasis and cycloplegia occur in 30– 60 min
and last about a day.
• It is preferred for cycloplegic refraction, but children may show transient
behavioural abnormalities due to absorption of the drug after passage into the
nasolacrimal duct. It is also used in iritis and uveitis.
3. Tropicamide:
• It has the quickest (20–40 min) and briefest (3–6 hours) action, but is a
relatively unreliable cycloplegic.
• However, it is satisfactory for refraction testing in adults and as a short acting
mydriatic for fundoscopy.
• The mydriatic action can be augmented by combining with phenylephrine

Nicotinic antagonist

Ganglionic Blockers
• Ganglionic blockers specifically act on the nicotinic receptors of both parasympathetic
and sympathetic autonomic ganglia.
• Some also block the ion channels of the autonomic ganglia.
• These drugs show no selectivity toward the parasympathetic or sympathetic ganglia
and are not effective as neuromuscular antagonists.
• Thus, these drugs block the entire output of the autonomic nervous system at the
nicotinic receptor.
• Except for nicotine, the other drugs mentioned in this category are nondepolarizing,
competitive antagonists.
• The responses of the nondepolarizing blockers are complex and mostly unpredictable.
• Therefore, ganglionic blockade is rarely used therapeutically, but often serves as a tool
in experimental pharmacology

Nicotine
• A component of cigarette smoke, nicotine [NIK-oh-teen], is a poison with many
undesirable actions.
• It is without therapeutic benefit and is deleterious to health.
• Depending on the dose, nicotine depolarizes autonomic ganglia, resulting first in
stimulation and then in paralysis of all ganglia.
• The stimulatory effects are complex and result from increased release of
neurotransmitters due to effects on both sympathetic and parasympathetic ganglia.
• For example, enhanced release of dopamine and norepinephrine may be associated
with pleasure as well as appetite suppression.
• The overall response of a physiologic system is a summation of the stimulatory and
inhibitory effects of nicotine.
• These include increased blood pressure and cardiac rate (due to release of transmitter
from adrenergic terminals and from the adrenal medulla) and increased peristalsis
and secretions. At higher doses, the blood pressure falls because of ganglionic
blockade, and activity in both the GI tract and bladder musculature ceases.

Neuromuscular Blocking Agents
• These drugs block cholinergic transmission between motor nerve endings and the
nicotinic receptors on the skeletal muscle.
• They possess some chemical similarities to ACh, and they act either as antagonists
(nondepolarizing type) or as agonists (depolarizing type) at the receptors on the
endplate of the NMJ.
• Neuromuscular blockers are clinically useful during surgery to facilitate tracheal
intubation and provide complete muscle relaxation at lower anesthetic doses, allowing
for more rapid recovery from anesthesia and reducing postoperative respiratory
depression.
A. Nondepolarizing (competitive) blockers
B. Depolarizing agents

• The first drug known to block the skeletal
NMJ was curare [kyooRAH-ree], which
native South American hunters of the
Amazon region used to paralyze prey.
• The development of the drug tubocurarine
[too-boe-kyoo-AR-een] followed, but it has
been replaced by other agents with fewer
adverse effects, such as cisatracurium [cis-
a-trah-CURE-ih-um], pancuronium [pan-
kure-OH-nee-um], rocuronium [roe-kyoor-
OH-nee-um], and vecuronium [ve-
KYOOroe-nee-um].
• Neuromuscular blockers should not be used
to substitute for inadequate depth of
anesthesia.

Mechanism of action
At low doses:
• Nondepolarizing agents competitively block ACh at the nicotinic receptors.
• That is, they compete with ACh at the receptor without stimulating it. Thus, these
drugs prevent depolarization of the muscle cell membrane and inhibit muscular
contraction.
• Their competitive action can be overcome by administration of cholinesterase
inhibitors, such as neostigmine and edrophonium, which increase the
concentration of ACh in the neuromuscular junction.
• Anesthesiologists employ this strategy to shorten the duration of the
neuromuscular blockade.
• In addition, at low doses the muscle will respond to direct electrical stimulation
from a peripheral nerve stimulator to varying degrees, allowing for monitoring of
the extent of neuromuscular blockade.

At high doses:
• Nondepolarizing agents can block the ion channels of the motor endplate.
• This leads to further weakening of neuromuscular transmission, thereby
reducing the ability of cholinesterase inhibitors to reverse the actions of the
nondepolarizing blockers.
• With complete blockade, the muscle does not respond to direct electrical
stimulation.

Actions:
• Not all muscles are equally sensitive to
blockade by competitive agents.
• Small, rapidly contracting muscles of the
face and eye are most susceptible and are
paralyzed first, followed by the fingers,
limbs, neck, and trunk muscles.
• Next, the intercostal muscles are affected
and, lastly, the diaphragm.
• The muscles recover in the reverse manner.

Pharmacokinetics:
Route of Administeration:
All neuromuscular-blocking agents are injected intravenously or occasionally
intramuscularly since they are not effective orally.
Absorption:
These agents possess two or more quaternary amines in their bulky ring structure that
prevent their absorption from the gut.
Distribution:
They penetrate membranes very poorly and do not enter cells or cross the blood–brain
barrier. Many of the drugs are not metabolized, and their actions are terminated by
redistribution.
Metabolism, excretion and elimination:
For example, pancuronium is excreted unchanged in urine. Cisatracurium is degraded
spontaneously in plasma and by ester hydrolysis.

• Note: Atracurium has been replaced by its isomer, cisatracurium. Atracurium
releases histamine and is metabolized to laudanosine, which can provoke
seizures. Cisatracurium, which has the same pharmacokinetic properties as
atracurium, is less likely to have these effects.]
• The amino steroid drugs vecuronium and rocuronium are deacetylated in the
liver, and their clearance may be prolonged in patients with hepatic disease.
• These drugs are also excreted unchanged in bile.
• The choice of an agent depends on the desired onset and duration of the
• muscle relaxation

Drug
Interactions:
Drugs such as
neostigmine,
physostigmine,
pyridostigmine,
and edrophonium
can overcome the
action of
nondepolariz
Drugs such as
desflurane act to
enhance
neuromuscular
blockade by
exerting a
stabilizing action
at the NMJ
gentamicin and
tobramycin inhibit
ACh release
CCB increase the
neuromuscular
blockade of
competitive
blockers

B. Depolarizing agents
• Depolarizing blocking agents work by depolarizing the plasma membrane of the muscle
fiber, similar to the action of ACh.
• However, these agents are more resistant to degradation by acetylcholinesterase (AChE)
and can thus more persistently depolarize the muscle fibers.
• Succinylcholine [suk-sin-il-KOE-leen] is the only depolarizing muscle relaxant in use
today.

Increase Ca influx----- contraction---- fasculation--- flacid paralysis

Actions:
• As with the competitive blockers, the respiratory muscles are paralyzed last.
• Succinylcholine initially produces brief muscle fasciculations that cause
muscle soreness.
• This may be prevented by administering a small dose of nondepolarizing
neuromuscular blocker prior to succinylcholine.
• Normally, the duration of action of succinylcholine is extremely short, due to
rapid hydrolysis by plasma pseudocholinesterase.
• However, succinylcholine that gets to the NMJ is not metabolized by AChE,
allowing the agent to bind to nicotinic receptors, and redistribution to plasma
is necessary for metabolism (therapeutic benefits last only for a few minutes)

Therapeutic uses:
• Because of its rapid onset of action,
succinylcholine is useful when rapid
endotracheal intubation is required during
the induction of anesthesia (a rapid action is
essential if aspiration of gastric contents is to
be avoided during intubation).
• It is also used during electroconvulsive shock
treatment.
Pharmacokinetics:
• Succinylcholine is injected
intravenously.
• Its brief duration of action results
from redistribution and rapid
hydroysis by plasma
pseudocholinesterase.
• Therefore, it is given by
continuous infusion to maintain a
longer duration of effect. Drug
effects rapidly disappear upon
discontinuation.

Parasympatholytics+MLT+3RD SEMSTER+BAASIR UMAIR.pptx

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