Cholinergic antagonists
Samuel Aguazim ( MD)
What are cholinergic
antagonists?
• Drugs that bind to cholinergic receptors
( muscarinic and/or nicotinic), but do not trigger the
usual intracellular response. The antagonize the
effects of acetylcholine
Name 3 subclasses of
cholinergic antagonists.
• 1. Muscarinic blockers
• 2. Neuromuscular blocking agents- inhibit the
efferent impulses to skeletal muscle via the
nicotinic muscle receptor (Nm)
• 3. Ganglionic blockers- inhibit the nicotinic
neuronal receptor (Nn) of both parasympathetic
and sympathetic ganglia
Muscarinic antagonists
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Give six examples of muscarinic blockers
1. atropine
2. scopolamine
3. homatopine
4. cyclopentolate
5. tropicamide
6. pirenzepine
Anti- muscarinic agents
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sites of action
1. Secretions by salivary, bronchial and sweat
glands.
2. The eye and cardiac responses mediated by
the vagus.
3. Urinary bladder and GI tract.
4. Gastric secretions.
• Note: All of the muscarinic antagonists are
competitive antagonists for the binding of
acetylcholine to the muscarinic receptor
Naturally occurring
• Atropine ( belladonna )
• Scopolamine
• Homatropine
The effect and side effects of these
drugs are the opposite of the drugs
considered in the previous chapter
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Eye: Mydriasis, cyclopedia ( blurred vision)
Skin : Reduced sweating, flushing
GI: Reduced motility and secretions
CVS: Increased Heart Rate ( High Doses)
Respiratory: Bronchial Dilation and
decreased secretion
• GU: Urinary retention
• CNS: drowsiness, hallucinations, coma
• ATROPINE – high affinity for muscarinic receptors.
acts both centrally and peripherally
• It causes reversible, nonselective blockade of
muscarinic receptors.
• Mydriasis, cycloplegia.
• Eneuresis in children
• Low doses- bradycardia.
• High doses—tachycardia
• Dilates cutaneous vasculature
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Atropine uses
In ophthalmology –mydriatic/ cycloplegic
Spastic disorders of GI and lower urinary tract.
To treat Organophosphate poisoning
To suppress respiratory secretions prior to
surgery.
Synthetic quaternary
ammonium antimuscarinic
agents.
• Ipratropium
• Propantheline
Synthetic tertiary amine
muscarinic antagonists
• Cyclopentolate
• Tropicamide
• Dicyclomine
• Pirenzipine
CNS
• Due to its greater lipid solubility,
scopolamine has significant CNS effects
even at low therapeutic doses.
• An adjunct for anesthesia due to an ability
to decrease short term memory.
• Motion sickness (scopolamine)
• Antipsychotic therapy: used to treat the
extrapyramidal symptoms
Eye
• Mydriasis
• Refract the eye during ophthalmic examinations.
• Caution : glaucoma
Heart
• Low doses initially produce bradycardia, but later
doses produce tachycardia.
• Some times in Surgery/catheterization
Lung
• Broncho -dilation: Ipratropium
• Mainly used as inhalation in treating asthma and
COPD.
• Atropine prior to surgery will decrease the
respiratory secretions
GI tract
• Salivary secretions decrease
• Can cause dry mouth and difficulty in swallowing
• Only Pirenzepine has some potency to
decrease hyperacidity..
Other uses
• With an opioid to relax the ureter in renal colic.
• To increase the capacity and decrease the
frequency of bladder contractions, i.e. enuresis
in children.
• To decrease the frequency of urination in spastic
paraplegia.
Toxic effects
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decreased concentration and memory
drowsiness
sedation
excitation
ataxia
asynergia
disorientation
hallucinations
coma
ATROPINE PSYCHOSIS
• Disorientation, confusion, recent loss of memory,
agitation, incoherent speech, restlessness,
hallucinations, anxiety and delirium.
• Treatment – symptomatic only and discontinue
the drug immediately.
Therapeutic uses of muscarinic
antagonists
• 1. Premedication
• · Atropine
• · Given before operations to prevent unwanted M
stimulation.
• · Want to eliminate bronchial secretions (don't want the
patient to choke on their own secretions)
• · Want to block vagal stimulation to the heart and lungs
(want to keep airways open)
• · During induction of anesthesia, there may be excessive
vagal stimulation, which we want to eliminate.
• Anticholinesterase toxicity
• Toxicity due to over dose of physostigmine and
other anticholinesterases
• Atropine is used to treat this condition by
blocking all M receptors.
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2. Antispasmodic
· Hyoscine N butyl Bromide
· A quaternary derivative
· Treats colic
3. Bronchodilator (asthma)
· Ipratropium
· A quaternary derivative
· Given by inhalation, get a local effect
• Homatropine
• · Much shorter action than atropine
• · It is the drug of choice when doing
investigations of the eye, since it dilates the
pupil for a short time only.
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4.Treatment of peptic ulcers
· Pirenzepine
· Selective M1 antagonist
· Not as good as H2 antagonists (e.g. cimetidine)
or proton pump inhibitors (e.g. omeprazole)
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5. Parkinson's disease
• · Benztropine, trihexiphenidyl
also used to treat the extrapyramidal symptoms due
to Antipsychotic drugs
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6. Motion sickness
· Hyoscine, scopolamine
ADVERSE EFFECT OF ATROPINE
• DRY MOUTH
• INHIBITION OF SWEATING ESPECIALLY IN
YOUNG CHILDREN
• TACHYCARDIA AND CUTANEOUS
VASODILATION
• BLURRING OF VISION
• HALLUCINATIONS AND DELIRIUM
MUSCARINIC EFFECTS
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REMEMBER
S --- salivation
L --- lacrimation
U --- urination
D --- diaphoresis
G --- GI
E --- Eye & emesis
GANGLIONIC BLOCKERS
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NICOTINE
TRIMETHAPHAN
MECAMYLAMINE
Ganglionic blockers work by interfering with
the postsynaptic action of acetylcholine.
They block the action of acetylcholine at the
nicotinic receptor of all autonomic ganglia.
These drugs are very rarely used clinically
SITE OF ACTION
• ALL NICOTINIC RECEPTORS
• IN ANS ( BOTH SNS AND PNS )
• IN CNS
NICOTINE
DOSAGE
GANGLION
• LOW DOSE
• STIMULATION
• HIGH DOSE
• BLOCK
CNS/ NICOTINE
• LOW DOSE- EUPHORIA,RELAXATION
• HIGH DOSEcentral respiratory paralysis
hypotension- medullary paralysis
PERIPHERAL EFFECTS
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COMPLEX
HR RAISES
B.P.- RAISES
GIT- MOTILITY RAISES
OTHERS
• TRIMETHAPHAN- SHORT
ACTING
• HTN EMERGENCIES
• used in surgery, particularly
neurosurgery, to produce a
relatively bloodless operative
field (controlled hypotension).
• MECAMYLAMINE- LONG
ACTING
CHR. CASES of HTN
Neuromuscular Blocking Drugs
They block the effects of acetylcholine by
interacting with nicotinic receptor.
Mainly during surgery to produce complete muscle
relaxation, without giving higher anesthetic
doses.
Neuro muscular blocking drugs
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Atracurium
Doxacurium
Mivacurium
Pancuronium
Rocuronium
Succinylcholine
Tubocurarine
Vecuronium
Atracurium
• safe in renal failure, used in critically ill patients
for mechanical ventilation.
• Short duration of action – so suitable for short
surgical procedures.
Rocuronium & Succinylcholine
• Rapid onset of action – so used mainly in
tracheal intubation in patients with gastric
contents.
Vecuronium – short duration of action , so
used in short surgical procedures.
Imp side effects
• Tubocurarine – induce histamine release
and also lower B.P.
• Pancuronium – Increased H.R.
• Succinylcholine – malignant
hyperthermia, hyperkalemia and increased
Intraocular pressure.