Cholinergics

Question 1

BETHANECHOL use?

Answer 1

• Muscarinic agonist.
USES
• Postoperative and postpartum urinary retention.
• Atony of the urinary bladder.

Question 2

CARBACHOL use?

Answer 2

• Both muscarinic and nicotinic agonist.
USES
• Miosis during surgery.
• Reduces intraocular pressure after cataract
surgery.

Question 3

Methacholine use?

Answer 3

• Muscarinic agonist.
USES
• Diagnosis of bronchial airway hyperreactivity in
subjects who do not have clinically apparent
asthma.

Question 4

Pilocarpine and its uses?

Answer 4

PILOCARPINE
• Partial muscarinic agonist.
• Tertiary amine
• Stable

PILOCARPINE: USES
• Second line agent for open angle glaucoma.
• Management of acute angle-closure glaucoma.
• Treatment of dry mouth due to radiotherapy for
cancer of head and neck.
• Treatment of dry mouth caused by Sjogren’s
Syndrome.

Question 5

AE of muscarinic agonists?

Answer 5

• The adverse effects mimic the effects of
generalized cholinergic stimulation:
• Sweating
• Salivation
• Flushing
• Low blood pressure
• Nausea
• Abdominal pain
• Diarrhea
• Bronchospasm

Question 6

What is Nicotine?

Answer 6

• Tertiary amine.
• Selective agonist of the nicotinic receptor.
• Depending on the dose, nicotine depolarizes
autonomic ganglia, resulting first in stimulation
and then in paralysis.
• Low doses: ganglionic stimulation by
depolarization.
• The response resembles simultaneous
discharge of both parasympathetic and
sympathetic nervous systems.

Question 7

Actions of Nicotine?

Answer 7

• CV system: Mainly sympathomimetic effects.
Increase in HR and BP due to catecholamine
release from nerve terminals and adrenal medulla.
• GI & urinary tracts: Mainly parasympathomimetic
effects: nausea, vomiting, diarrhea, voiding of
urine.
• Secretions: Stimulation of salivary and bronchial
secretions.
• High doses: ganglionic blockade and
neuromuscular blockade

Question 8

What is Nicotine acute poisoning? Nicotine use?

Answer 8

• Symptoms of acute, severe nicotine
poisoning: nausea, salivation, abdominal pain,
vomiting, diarrhea, cold sweat, mental confusion
and weakness.
• The blood pressure falls, the pulse is weak.
• Death may occur from paralysis of respiratory
muscles and/or central respiratory failure.
Nicotine use: • Smoking cessation therapy.

Question 9

List of INDIRECT-ACTING CHOLINERGIC AGENTS

ANTICHOLINESTERASES

Answer 9

1. Edrophonium
2. Carbamates
   • Physostigmine
   • Neostigmine
   • Pyridostigmine
3. Organophosphates
   • Echothiophate
   • Parathion & Malathion
   • Sarin

Question 10

MOA of edrophonium, carbonates, and organophosphates?

Answer 10

• Edrophonium binds reversibly to the active site
of the enzyme. The enzyme-inhibitor complex
doesn’t involve a covalent bond and is shortlived.
• Carbamates form a covalent bond with the
enzyme.
• Organophosphates phosphorylate the enzyme.
The covalent bond formed is extremely stable
and hydrolyzes very slowly. • The phosphorylated enzyme may undergo a process called ageing.• This process strengthens the phosphorousenzyme bond.

Question 11

CNS effects of anticholinesterase?

Answer 11

• In low concentrations liposoluble cholinesterase
inhibitors cause CNS activation.
• In higher concentrations they cause convulsions,
which may be followed by coma and respiratory
arrest.

Question 12

Net cv effect of anticholinesterase

Answer 12

• The net CV effects of moderate doses of
cholinesterase inhibitors consist of:
• Modest bradycardia
• Fall in cardiac output
• Increased vascular resistance
• Increase in blood pressure

Question 13

CHolinesterase inhibitors effect on vascular smooth muscle?

Answer 13

Cholinesterase inhibitors have minimal effects on vascular smooth muscle because most
vascular beds lack cholinergic innervation (coronary vasculature is an exception).
At moderate doses, cholinesterase inhibitors cause an increase in systemic vascular
resistance and blood pressure due to activation of sympathetic ganglia in the case of
LD140218 8
quaternary ammonium compounds and also at central sympathetic centers in the case of
liposoluble agents.

Question 14

EDROPHONIUM?

Answer 14

• Quaternary ammonium.
• Does not enter CNS.
USES
• Used in diagnosis of myasthenia gravis.
Edrophonium IV leads to rapid increase in
muscle strength.
• Used to reverse the neuromuscular block
produced by non-depolarizing muscular
blockers.

Question 15

Physostigmine uses?

Answer 15

• Tertiary amine.
• Can enter and stimulate CNS.
USES
• Treatment of overdoses of anticholinergic
drugs.

Question 16

NEOSTIGMINE?

Answer 16

• Quaternary ammonium.
• Does not enter CNS.
USES
• Postoperative urinary retention.
• Reversal of effects of non-depolarizing
neuromuscular blockers after surgery.
• Treatment of myasthenia gravis

Question 17

Pyridostigmine?

Answer 17

• Quaternary ammonium.
• Does not enter CNS.
USES
• Treatment of myasthenia gravis. Most commonly used for this indication?

Question 18

Organophosphates?

Answer 18

ECHOTHIOPHATE
• Rarely used for glaucoma. 
ORGANOPHOSPHATES: INSECTICIDES
MALATHION
PARATHION
ORGANOPHOSPHATES: NERVE AGENTS
SARIN
• Among the most potent synthetic toxic agents
known.

Question 19

Alzheimer’s anticholinesterase?

Answer 19

• The mainstay of therapy for patients with
Alzheimer disease is the use of centrally acting
acetylcholinesterase inhibitors.
• Donepezil
• Rivastigmine
• Galantamine

Question 20

Reactivator of Ache?

Answer 20

• If given before ageing has
occurred, drugs like
pralidoxime split the
phosphorous-enzyme bond.
• Pralidoxime can be used as
cholinesterase regenerator
for organophosphate
insecticide poisoning.

Question 21

Atropine? uses?

Answer 21

• Reversible competitive antagonist at muscarinic
receptors.
• Prevents acetylcholine from binding at muscarinic
receptors.
• Tertiary amine: both central and peripheral
muscarinic blocker
• Eye: Mydriasis. Cycloplegia.
• GI: Reduces gastric motility.
• Urinary system: Decreases hypermotility of
urinary bladder.

Question 22

Atropine effect on CV system? Secretions?

Answer 22

Cardiovascular system:
• Low doses: bradycardia. Due to blockade of
presynaptic M2 receptors that normally inhibit
ACh release.
• Moderate to high therapeutic doses: Blockade
of atrial M2 receptors: tachycardia.
Secretions:
• Salivary, sweat and lachrymal glands are
blocked.
• Inhibition of sweat glands may cause high body
temperature.

Question 23

Atropine uses clinically?

Answer 23

• Antispasmodic: to relax GI tract and bladder.
• Antidote for cholinergic agonists.
• To block respiratory tract secretions prior to
surgery.

Question 24

Atropine AE?

Answer 24

• Dry mouth, blurred vision, sandy eyes,
tachycardia, constipation urinary retention.
• Effects on CNS: restlessness, confusion,
hallucinations, delirium, which may progress to
depression, collapse of the circulatory and
respiratory systems and death.

Question 25

Scopolamine uses?

Answer 25

USES
• Prevention of motion sickness.
• To block short-term memory: sometimes used in
anaesthetic procedures.

Question 26

QUATERNARY AMMONIUM

MUSCARINIC ANTAGONISTS? Uses?

Answer 26

IPRATROPIUM AND TIOTROPIUM
• Used as inhalational drugs in the treatment of
chronic obstructive pulmonary disease (COPD).
• Also used as inhalational drugs in asthma.

Question 27

TERTIARY AMINE MUSCARINIC ANTAGONISTS?

Answer 27

HOMATROPINE
TROPICAMIDE
• Used as mydriatic for fundoscopy.
• Produce mydriasis with cycloplegia.
• Preferred to atropine because of shorter
duration of action.
BENZTROPINE
TRIHEXYPHENIDYL
• Used to treat Parkinson’s disease and the
extrapyramidal effects of antipsychotic drugs.

Question 28

GLYCOPYRROLATE

TOLTERODINE

Answer 28

• Used orally to inhibit GI motility.
• Used parenterally to prevent bradycardia during
surgical procedures.
Antimuscarinic
Tolterodine- • Used for overactive bladder.

Question 29

CONTRAINDICATIONS OF

ANTIMUSCARINIC AGENTS?

Answer 29

• Contraindicated in patients with angle-closure
glaucoma.
• Should be used with caution in patients with
prostatic hypertrophy and in the elderly

Question 30

Ganglion blockade may occur by the following

mechanisms?

Answer 30

• By prolonged depolarization:
Nicotine.
• By antagonism of nicotinic receptors:
Hexamethonium and mecamylamine.
• Ganglion blocking drugs are used rarely
because more selective autonomic blocking
agents are available.
• Effects of ganglion-blockers can be predicted by
a knowledge of which division of the autonomic
nervous system exercises dominant control of
various organs.
• The effect of the ganglion blocker is to remove
the dominant control.

Question 31

NEUROMUSCULAR BLOCKERS categories?

Answer 31

• COMPETITIVE ANTAGONISTS
(NONDEPOLARIZING BLOCKERS)
• AGONISTS (DEPOLARIZING BLOCKERS)

Question 32

NONDEPOLARIZING BLOCKERS name, moa, use?

Answer 32

TUBOCURARINE
• Prototype of the nondepolarizing drugs.
MECHANISM OF ACTION
• Competitive antagonists.
USES
• Adjuvant drugs in anaesthesia during surgery to
relax skeletal muscle.

Question 33

DEPOLARIZING BLOCKERS?

Answer 33

SUCCINYLCHOLINE
• Binds to the nicotinic receptor and depolarizes
the junction. Persists in the synaptic cleft,
stimulating the receptor: receptor
desensitizes. This leads to flaccid paralysis.
USES
• Rapid endotracheal intubation.
• ECT.

Question 34

Depolarizing blocker adverse effect?

Answer 34

• Malignant hyperthermia: Due to excessive
release of Ca2+ from the SR.
• Most incidents due to combination of
succinylcholine and an halogenated anesthetic.
• Treatment: dantrolene. Blocks release of Ca2+
from SR.

Question 35

INHIBITORS OF ACETYLCHOLINE

SYNTHESIS?

Answer 35

HEMICHOLINIUM-3
• Blocks the CHT.
• Prevents uptake of choline required for ACh
synthesis.
• Research tool.

Question 36

INHIBITORS OF ACETYLCHOLINE STORAGE?

Answer 36

VESAMICOL
• Vesamicol blocks the ACh-H+ antiporter that is
used to transport ACh into vesicles, thereby
preventing the storage of ACh.
• Research tool.

Question 37

INHIBITORS OF ACETYLCHOLINE RELEASE?

Answer 37

BOTULINUM TOXIN
• Inhibits acetylcholine release.
• Injected locally into muscles for
treatment of several diseases
involving muscle spasms.
• Also approved for cosmetic
treatment of facial wrinkles.