Download 8. Anti-cholinergics

ANTI-CHOLINERGICS
Asmah Nasser, M.D.
ANTI-CHOLINERGICS
Cholinergic blockers( Anti-cholinergics or
parasympatholytics) - class of drugs that block
the actions of acetylcholine in the PSNS
 Cholinergic blockers allow the SNS to dominate
and, therefore, have many of the same effects as
the adrenergics.


Muscarinic receptor blockers

Nicotinic receptor blockers
M1
Secretory
glands
salivation, stomach acid, sweating, lacrimation
M2
Heart
Decreases heart rate  bradycardia
M3
Smooth
Contraction of smooth muscles (some) 
muscle
diarrhea, bronchospasm, urination
(GI/GU/Resp)
M3
Pupil and
ciliary
muscle
Contracts  Miosis
Increased flow of aqueous humor
Nm
Skeletal
muscle end
plate
Contraction of skeletal muscle
Nn
Autonomic
ganglia,
Adrenal
Medulla
Secretion of Epinephrine
Controls ANS
WHAT ARE THE DRUG TARGETS?
Block/Antagonize Muscuranic Receptors
 Prevent the release of acetylcholine
 Prevent formation of acetylcholine
 Deplete acetyl choline storage

MUSCARINIC RECEPTOR BLOCKERS
1.Natural alkaloids:
Atropine, Scopolamine
2.Semi synthetic drugs :

Homoatropine, tropicamide, (short acting)

Benztropine, ipratropium glycopyrrolate,
Dicyclomaine
ATROPINE
Muscarinic receptor blocker
 Not hydrolyzed by cholinesterase, long duration
of action
 Actions of Atropine:

1.
Decreased salivary, bronchial and sweat
secretion
2.
Mydriasis and cyloplegia (loss of
accommodation reflex)
3.
Tachycardia
4.
Constipation
5.
Urinary retention
6.
Excitation /hallucinations
USES OF ATROPINE

Muscuranic Blocker

To produce mydriasis in refraction error testing
(short acting preparations of atropine are
preferred)

To treat Heart block, Bradycardia

To treat Cholinesterase inhibitors /
Oragnaophosphate (OP)pesticides poisoning

Anti-Diarrheal agent
ATROPINE

Contrindications of Atropine:





Glaucoma (closed angle)
Urinary retention
Benign prostatic hypertrophy
Paralytic Ileus
Myasthenia Gravis
OTHER MUSCARINIC BLOCKERS
 Tropicamide:
which acts for 4 hours is
preferred to produce mydriasis and cycloplegia in
refraction error testing and fundoscopy

Benztropine (drug of choice) for treatment of
drug-induced Parkinsonism

Ipratropium bromide: Bronchial asthama

Scopolamine: to prevent Motion sickness
SCOPOLAMINE
Competitive Muscuranic receptor antagonist
 M1 > M2 and M3
 Reduces Nausea
 Uses: Prevent sea sickness, used in motion
sickness, nausea, etc
 Used in a transdermal patch because of CNS side
effects

IPRATROPIUM BROMIDE
Muscuranic Anatagnist
 Blocks M3 (for smooth muscle contraction)
 If used inhaled, will prevent bronchospams 
bronchodilation
 Decreases the secretions made in the respiratory
mucosa
 Uses: Asthma

NICOTINIC RECEPTOR BLOCKERS
There are 2 subtypes of Niotinic Receptors:
 Nn and Nm
 Nn is found in nerves, at the ganglion
 Nm is found on muscles.

NICOTINIC RECEPTOR BLOCKERS
Ganglionic blocking drugs: Trimethaphen
Neuromuscular blockers :
A.
Nondepolarizing: D-tubocurarine , Atracurium
B.
Depolarizing: Succinylcholine
GANGLIONIC BLOCKING DRUGS

Blocks the Sympathetic and Parasympathetic ANS.

Effects are dependant on the organ sympathetic or
parasympathetic activity in that organ is reduced

Side effects are combined with both Symapathetic and
Parasynmpathetic Symptoms (depends on what tone
that the organ is predominantly supplied by)

Hexamethonium : Not used

Trimethaphen: Used to treat severe hypertensive crises
GANGLIONIC BLOCKERS
Trimethaphen
 Nn receptor antagonist. Blocks sympathetic and
parasympathetic nervous system
 Uses: Hypertensive Crsis
 Side effects: Mixed loss of Sympathetic
(hypotension) and Parasympathetic Nervous
System (tachycardia, constipation, urinary
rentention, dry mouth, etc…)

HEMICHOLINIUM
Indirect Cholinergic Antagonist
 Blocks reuptake/recycle of Choline from the
synapse to the pre-synaptic neuron
 Not in clinical use

SKELETAL MUSCLE RELAXANTS
Asmah Nasser, M.D.
NEUROMUSCULAR BLOCKERS
Nm blockers blocks acetylcholine at the Nm

receptor. Used in Surgery for skeletal muscle
relaxation
Non-depolarizing
A.



B.
Long acting: Tubocurarine, Pancuronium, Doxacuraium
Intermediate acting: Atracurium
Short acting: Miyacurium
Depolarizing: Succinylcholine (shorting acting)
NON-DEPOLARIZING NM BLOCKER
Example: Turbocurarine (long acting)
 MOA: After blocking NM receptors, they prevent
depolarization of muscle membrane and muscle
contraction
 Halothene and Aminoglycosides increase the
actions of Nm blockers
 Affinity for Nm not much higher than Nn
 Side effects:



Ganglionic blocker  hypotension
Releases histamine  Hypotension, bronchospasm
OTHER NON-DEPOLARIZING ANTAGONISTS

Atracurium
Metabolism: By plasma Cholinesterase
 Safe in patients with Renal Failure
 Intermediate Duration of Action (15 minutes)


Miyacurium
Short acting (minutes)
 Used in short procedures (intubations)

DEPOLARIZING NM BLOCKERS:
SUCCINYLCHOLINE





It stimulates the Nm receptor, similar to Ach
Persists at receptor at high concentration, because it
is not destroyed by AChE at the Nm junction
“Desensitizes” the end plate by occupying the
receptors and causing a “persistent depolarization”
leads to flaccid paralysis of muscle
Rapid onset and short duration of action (4-5
minutes) than other Nm blockers
Used mostly in very short procedures (intubation)
SIDE EFFECTS OF SUCCINYLCHOLINE
Is metabolized rapidly by plasma
pseudocholinestrase.
 Side effect:

Therefore pts who have a congenital deficiency is
pseudocholinesterase can’t metabolize
Succinylcholine  toxicity “Succinylcholine Apnea”
 Malignant hyperthermia
 Hyperkalemia  Arrythmias

ANTIDOTE?
Neostigmine is used to reserve the effects of Nondepolarizing agents.
 It inhibits the cholinesterase enzyme, increasing
the amount of acetylcholine in the synapse,
displacing Nm antagonists from the post-synaptic
receptor.

MALIGNANT HYPERTHERMIA



Is an autosomal dominant genetic disorder of
skeletal muscle
It is associated with mutations in the gene for
the skeletal muscle ryanodine receptor (RYRl),
the calcium release channel of the sarcoplasmic
reticulum
The specific biochemical abnormality is an
increase in free calcium concentration in skeletal
muscle cells
MALIGNANT HYPERTHERMIA



Rapid onset of hypertension and tachycardia, severe
muscle rigidity, hyperthermia, hyperkalemia, and
acid-base imbalance with acidosis, following exposure
to a triggering agent.
Is a rare but important cause of anesthetic morbidity
and mortality.
Occurs in susceptible individuals who undergoes
general anesthesia with inhaled agents (halothene)
and skeletal muscle relaxants( eg, succinylcholine).
TREATMENT OF MALIGNANT
HYPERTHERMIA
Dantrolene :
 MOA: Prevents calcium release from the
sarcoplasmic reticulum
WHAT TO KNOW!
Know the different Cholinergic receptors!
 Uses of Atropine, Benztropine, Ipatropium
 Know about Ganglionic blockers, their side
effects (and why they get those side effects).
Know about the use of Trimethaphan
 Know the difference between Depolaring and
Non-Depolaring Neuromuscular blockers
 Know about Malignant Hyperthermia

PRETEST QUESTION
Of the many types of adrenergic receptors found
throughout the body, which is most likely
responsible for the cardiac stimulation that is
observed following an intravenous injection of
epinephrine?
 a. α1-adrenergic receptors
 b. α2-adrenergic receptors
 c. β1-adrenergic receptors
 d. β2-adrenergic receptors
 e. β3-adrenergic receptors

PRETEST QUESTION
Applied to the skin in a transdermal patch
(transdermal therapeutic delivery system), this
drug is used to prevent or reduce the occurrence
of nausea and vomiting that are associated with
motion sickness.
 a. Diphenhydramine
 b. Chlorpromazine
 c. Ondansetron
 d. Dimenhydrinate
 e. Scopolamine

PRETEST QUESTION
Which of the following antimuscarinic drugs is
used by inhalation in the treatment of bronchial
asthma?
 a. Dicyclomine hydrochloride
 b. Cyclopentolate hydrochloride
 c. Ipratropium bromide
 d. Methscopolamine bromide
 e. Trihexyphenidyl hydrochloride

PRETEST QUESTION
A male patient is brought to the emergency
department (ED) following ingestion of an
unknown substance. He is found to have an
elevated temperature, hot and flushed skin,
dilated pupils, and tachycardia. Of the following,
which would most likely cause these findings?
 a. Propranolol
 b. Methylphenidate
 c. Prazosin
 d. Guanethidine
 e. Atropine

PREEST QUESTION
Of the following, which will not be blocked by
atropine and scopolamine?
 a. Bradycardia
 b. Salivary secretion
 c. Bronchoconstriction
 d. Skeletal muscle contraction
 e. Miosis

PRETEST QUESTION
Practice Question
Competitive Antagonists at the Nm junction
include which of the following?
A. Dantrolene
B. Atracurium
C. Mecamylamine
D. Isoflurophate
E. Succinylcholine

Practice Question

A.
B.
C.
D.
E.
Hereditary deficiency in what enzyme can lead
to prolonged side effects of Succinylcholine?
G6PD
Plasma Cholinesterase
Pseudocholinesterase
Cytochrome Oxidase
Liver transaminase
Practice Question

A.
B.
C.
D.
E.
Dantrolene is the drug of treament for
Malignant hypertherma because:
Dantrolene blocks Ca2+ release from the SR
Dantrolene induces contraction of skeletal
muscle
Dantrene increases the rate of succinylcholine
metabolism
Succinylcholine binding to the Nicotinic receptor
is blocked by dantrolene
Dantrolene acts centrally to reduce fever
Practice Questions
Which of the following agents, when applied
topically to the eye, would induce both
mydriasis and cycloplegia?
A. Phenylephrine
B. Carbachol
C. Prazosin
D. Atropine
Practice Question
Neostigmine would be expected to reverse which
one of the following conditions?
A. Paralysis of skeletal muscle by a competitive
(non-depolarizing) muscle relaxant
B. Paralysis of skeletal muscle by depolarizing
muscle relaxant
C. Cardiac slowing induced by stimulation of the
vagus nerve
D. Pupillary miosis induced by bright light