This presentation deals with the various cholinergic (acetylcholine) and anti-cholinergic drugs (atropine) alongwith a brief description of the various muscarinic receptors and nicotinic receptors. Also, it includes various agonists & antagonists with a brief description of organophosphorous poisoning at the end.

1. Cholinergic system and
drugs
Dr. Karun Kumar
JR-II
Dept. of Pharmacology

11. Ach receptor agonists
1. Direct acting agonists  Bind & activate Ach rec.
a) Choline esters  Ach, Bethanechol, Carbachol
b) Plant alkaloids  Muscarine, Nicotine,
Pilocarpine, Arecoline
c) Synthetic drugs  Cevimeline, Varenicline,
Tremorine, Oxotremorine

12. 2. Indirect acting agonists (Anti-chE)
i) Reversible anti-chE
a) Natural alkaloid  Physostigmine
b) Others  Edrophonium, Neostigmine,
Pyridostigmine, Donepezil, Galantamine,
Rivastigmine, Ambenonium, Demecarium
ii) Irreversible anti-chE  OPs, Echothiophate,
Isoflurophate, Malathion,
Propoxur, Paraoxon, Carbaryl

13. Clinical uses
• Bethanechol
1. Urinary retention (Postoper. Or neurogenic bld.)
2. GIT atony (Expel gases, paralyitc ileus)
3. Xerostomia (Salivary gland malfunc., Sjogren’s)
• Methacholine  MCT (bronchial asthma)
• Carbachol  Miosis during ophthalmic surgery
• Pilocarpine
1. Ophthalmic  Glaucoma, mydr., break adhesions
2. Sialagogue  Xerostomia (laryng. surg., radioth.)

14. • Nicotine  Smoking cessation programs
• Pilocarpine  Xerostomia, Glaucoma
• Cevimeline  Xerostomia
• Varenicline  Smoking cessation
• Edrophonium  Diff. b/w myasthenic & c. crisis
• Donepezil, Galantamine & Rivastigmine  AD
• Pyridostigmine  Myasthenia gravis
• Echothiophate  Eye (glaucoma)
• Malathion  Lice (Pediculosis)

15. • Neostigmine (NO CNS penetration – Quat. Amine)
Muscarinic
1. Postop. Paralytic ileus
2. Postop. urinary retention
Nicotinic
1. Myasthenia gravis (Oral  15-30 mg; 0.5-2.5 mg i.m/s.c)
2. Cobra bite
3. Curare poisoning
• Physostigmine (CNS penetr. – Tertiary amine)
1. Antidote in atropine poisoning (2 mg i.m./i.v.)
2. Ophthalmic (Glaucoma, mydr., adhesions break)

17. Poisoning
• Organophosphates
1. Insecticides  Malathion, Parathion, Dyflos
2. Nerve gases  Soman, Sarin
3. Ophthalmic agents  Echothiophate,
Isoflurophate
• Carbamates
1. Reversible  Physostigmine, Neostigmine,
Pyridostigmine, Edrophonium,
Rivastigmine, Donepezil, Galantamine
2. Irreversible  Carbaryl, Propoxur

18. Anti-chE poisoning
M  Miosis
U  Urination
S  Sec. ↑ (Salivation, lacrimation & sweating)
C  Cardiac contraction & conduction slows
A  Abdominal cramps
R  Redn. In i.o.t. (esp. in glaucoma)
I  Inc. (↑) GI motility
N  NO dependent vasodilatation
I  Inc. sec. from GIT & tracheobronchial tract
C  Constriction of tracheobronchial tract

19. Treatment
1. Termination of further exposure to the poison
2. Maintain patent airway  PPV
3. Supportive measures
4. Specific antidotes
a) Atropine  Counteracts muscarinic symptoms
Dose  2 mg i.v. every 10 mins. Till atr. Signs
b) ChE reactivator  Pralidoxime, Diacetylmonoxime
Dose  1-2 gms slow i.v. infusion

20. Review Questions
1. A woman with facial muscle spasms is treated with
an agent that inhibits the release of acetylcholine.
Which side effect is most likely to occur in this
patient?
(A) bradycardia
(B) urinary incontinence
(C) dry mouth
(D) diarrhea
(E) constriction of the pupils

21. 2. A man receives an injection of epinephrine to treat
an allergic reaction to a bee sting. Which effect
would result from this treatment?
(A) increased glucose absorption from the gut
(B) increased hepatic output of glucose
(C) increased uptake of glucose by skeletal muscle
(D) increased formation of glycogen
(E) increased conversion of glucose to fat

22. 3. A man complains of dry mouth after radiation
therapy for throat cancer, and he is treated with
cevimeline. Which mechanism produces the
therapeutic effect of this drug?
(A) activation of muscarinic M2 receptors
(B) increased formation of IP3
(C) increased cAMP levels
(D) increased cGMP levels
(E) increased potassium efflux

23. 4. A woman in a smoking cessation program receives
a drug that reduces craving and withdrawal effects.
Which effect results from receptor activation by this
drug?
(A) sodium influx
(B) potassium efflux
(C) increased cAMP
(D) increased cGMP
(E) IP3 formation

24. 5. A man receives a drug that increases cGMP levels.
Which adverse effect is most likely to result from this
medication?
(A) constipation
(B) cough
(C) dry mouth
(D) sedation
(E) headache

25. 6. An agricultural worker is brought to the
emergency department after abrupt onset of bowel
and bladder incontinence and muscle weakness. He
is given oxygen and antidotal drug treatments. Which
drug mechanism would increase muscle strength in
this patient?
(A) blockade of muscarinic receptors
(B) activation of nicotinic receptors
(C) increased neurotransmitter degradation
(D) induction of drug-metabolizing enzymes

26. 7. A 30-year-old woman undergoes abdominal
surgery. In spite of minimal tissue damage, complete
ileus (absence of bowel motility) follows, and she
complains of severe bloating. She also finds it
difficult to urinate. Mild cholinomimetic stimulation
with bethanechol or neostigmine is often effective in
relieving these complications of surgery. Neostigmine
and bethanechol in moderate doses have
significantly different effects on which one of the
following?
(A) Gastric secretion
(B) Neuromuscular end plate
(C) Salivary glands
(D) Sweat glands
(E) Ureteral tone

27. 8. Parathion has which one of the following
characteristics?
(A) It is inactivated by conversion to paraoxon
(B) It is less toxic to humans than malathion
(C) It is more persistent in the environment than DDT
(D) It is poorly absorbed through skin and lungs
(E) If treated early, its toxicity may be partly reversed
by pralidoxime

28. 9. Ms Brown has been treated for myasthenia gravis
for several years. She reports to the emergency
department complaining of recent onset of weakness
of her hands, diplopia, and difficulty swallowing. She
may be suffering from a change in response to her
myasthenia therapy, that is, a cholinergic or a
myasthenic crisis. Which of the following is the best
drug for distinguishing between myasthenic crisis
(insufficient therapy) and cholinergic crisis (excessive
therapy)?
(A) Atropine
(B) Edrophonium
(C) Physostigmine
(D) Pralidoxime
(E) Pyridostigmine

29. 10. A crop duster pilot has been accidentally exposed
to a high concentration of a highly toxic agricultural
organophosphate insecticide. If untreated, the cause
of death from such exposure would probably be
(A) Cardiac arrhythmia
(B) Gastrointestinal bleeding
(C) Heart failure
(D) Hypotension
(E) Respiratory failure

30. 11. Mr Green has just been diagnosed with
dysautonomia (chronic idiopathic autonomic
insufficiency). You are considering different therapies
for his disease. Pyridostigmine and neostigmine may
cause which one of the following?
(A) Bronchodilation
(B) Cycloplegia
(C) Diarrhea
(D) Irreversible inhibition of acetylcholinesterase
(E) Reduced gastric acid secretion

31. 12. Parasympathetic nerve stimulation and a slow
infusion of bethanechol will each:
(A) Cause ganglion cell depolarization
(B) Cause skeletal muscle end plate depolarization
(C) Cause vasodilation
(D) Increase bladder tone
(E) Increase heart rate

32. 13. Actions and clinical uses of muscarinic
cholinoceptor agonists include which one of the
following?
(A) Bronchodilation (asthma)
(B) Improved aqueous humor drainage (glaucoma)
(C) Decreased gastrointestinal motility (diarrhea)
(D) Decreased neuromuscular transmission and
relaxation of skeletal muscle (during surgical
anesthesia)
(E) Increased sweating (fever)

33. 14. Which of the following is a direct-acting
cholinomimetic that is lipid-soluble and is used to
facilitate smoking cessation?
(A) Acetylcholine
(B) Bethanechol
(C) Neostigmine
(D) Physostigmine
(E) Varenicline

34. 15. A 3-year-old child is admitted after taking a drug
from her parents’ medicine cabinet. The signs
suggest that the drug is an indirect-acting
cholinomimetic with little or no CNS effect and a
duration of action of about 2–4 h. Which of the
following is the most likely cause of these effects?
(A) Acetylcholine
(B) Bethanechol
(C) Neostigmine
(D) Physostigmine

35. 16. Which of the following is the primary second-
messenger process in the contraction of the ciliary
muscle when focusing on near objects?
(A) cAMP (cyclic adenosine monophosphate)
(B) DAG (diacylglycerol)
(C) Depolarizing influx of sodium ions via a channel
(D) IP3 (inositol 1,4,5-trisphosphate)
(E) NO (nitric oxide)