Cholinergic 2

Question 1

1. What are the different categories of cholinergic antagonists?

Answer 1

1. muscarinic receptor antagonists
2. nicotinic receptor antagonists – ganglion blockers, NMJ blockers (Nm)
3. drugs that act presynaptically

Question 2

2. What are the two belladonna alkaloids?

Answer 2

Atropine and scopolamine – these are plant metabolites with nitrogen-containing ring structures. Both tertiary amines?!

Question 3

3. What is Atropine? (mechanism and actions)

Answer 3

Competitive muscarinic receptor preventing ACh from binding. It is a tertiary amine so blocks both central and peripheral muscarinic receptors.
Eye → mydriasis (dilation of pupil), cycloplegia (paralysis of ciliary muscle of eye)
GI → reduces gastric motility
Urinary system → decreases hypermotility of urinary bladder
CV → bradycardia (low dose), tachycardia (moderate to high dose)
Secretions → decrease salivary sweat and lachrymal [the blockage of sweat glands may cause high body temp]

Question 4

4. What is the effect of dose amt on the cardiovascular system?

Answer 4

Low dose → blockade of PRESYNAPTIC M2 (inhibitory) receptors thereby increasing ACh releases which would normally be decreased by binding of ACh to M2 PRESYNAPTIC receptors (inhibiting an inhibitor)
Moderate to High dose → blockade of ATRIAL M2 receptors leading to tachycardia
*High dose of anti-muscarinic agents may cause cutaneous vasodilation = “atropine flush” [unknown mechanism]

Question 5

5. What is atropine used for?

Answer 5

1. mydriasis and cycloplegia
2. antispasmodic to relax GI tract and bladder
3. antidote for cholinergic agonist
4. Antidote for mushroom poisoning due to muscarine
5. Block respiratory tract secretions prior to surgery

Question 6

6. What are the adverse effects of atropine?

Answer 6

Dry mouth, blurred vision, sandy eyes, tachycardia, constipation, CNS effects (restlessness, confusion, hallucinations, delirium, depression, circulatory and respiratory collapse → death)

Question 7

7. What is Scopolamine? (mechanism and use)

Answer 7

Scopolamine is a muscarinic antagonist that is used to prevent motion sickness or block short term memory.

Question 8

8. What are Ipratropium and Tiotropium?

Answer 8

These are quarternary ammonium muscarinic antagonist. These drugs are used as inhalational drugs in the treatment of COPD or asthma.

Question 9

9. What are Homatropine, Cyclopentolate, and Tropicamide?

Answer 9

These are tertiary amine muscarinic antagonists. These drugs are used in ophthalmology to produce mydriasis WITH cycloplegia. These drugs are preferred to atropine b/c of shorter duration of action.

Question 10

10. What are Benztropine and Trihexyphenidyl?

Answer 10

These are tertiary amine muscarinic antagonists. They are used to treat Parkinson’s disease and extrapyramidal effects of antipsychotic drugs.

Question 11

11. What is Glycopyrrolate?

Answer 11

Glycopyrrolate is a muscarinic antagonist that does not cross the blood brain barrier. It is consumed orally to inhibit GI motility or parenterally to prevent bradycardia during surgical procedures.

Question 12

12. What is Tolterodine?

Answer 12

A muscarinic antagonist used to treat an overactive bladder.

Question 13

13. What are the contraindications of antimuscarinic agents?

Answer 13

1. pts with angle-closure glaucoma – treat glaucoma with miosis (pupil constriction) so with these pts you don’t want to give pupil dilators b/c then the fluid will not be able to escape through the canal increasing the pressure even more
2. pts with prostatic hypertrophy
3. elderly

Question 14

14. What are the two mechanisms of ganglion (Nn) blockers?

Answer 14

1. prolonged depolarization (ex. Nicotine) – first it acts as an agonist then desensitizes and becomes an antagonist
2. antagonisms of nicotinic receptors (ex. Hexamethonium, mecamylamine, trimethaphan)

Question 15

15. What are the uses of ganglion blockers?

Answer 15

Ganglion blockers (ex. Hexamethonium, mecamylamine, trimethaphan) were originally used for HTN, but due to their adverse side effects they have been replaced by superior antihypertensive agents. Ganglion blockers can block both sympathetic or parasympathetic Nn. Whatever the dominant innervation (ex. cardiac with parasympathetic) is, the opposite will occur when ganglion blockers are used.

Question 16

16. In what body structures are the sympathetics the predominant tone?

Answer 16

1. Arterioles (sympathetics – adrenergic)
2. Veins (sympathetics - adrenergic)
3. Sweat (sympathetic – cholinergic)

Question 17

17. What body structures have parasympathetic as the predominant tone?

Answer 17

1. heart
2. Iris
3. Ciliary muscles
4. GI tract
5. Urinary bladder
6. Salivary glands

Question 18

18. What are the two classes of neuromuscular blockers?

Answer 18

1. competitive antagonists (nondepolarizing blockers)

2. agonists (depolarizing blockers)

Question 19

19. What is Tubocurarine? (mechanism and use)

Answer 19

Tubocurarine is a competitive antagonist ,nondepolarizing blocker. It is used as an adjuvant drug in anesthesia during surgery to relax skeletal muscle.

Question 20

20. What is Succinylcholine? (mechanism and use)

Answer 20

Succinylcholine binds to the nicotinic receptor and depolarizes the junction. It remains in the synaptic cleft continuing to stimulate the receptor thereby desensitizing it. This leads to flaccid paralysis. (activates then inactivates) This drug is used when rapid endotracheal intubation is needed and electroconvulsive therapy (ECT).

Question 21

21. What are the adverse side effects of depolarizing muscarinic agents?

Answer 21

Depolarizing agents may cause malignant hyperthermia due to excessive release of calcium from the sarcoplasmic reticulum. Most incidents are due to combination therapy of succinylcholine and an halogenated anesthetic. Treatment for malignant hyperthermia includes Dantrolene which blocks the release of Ca2+ from the SR.

Question 22

22. What are the categories of drugs that act presynaptically?

Answer 22

1. inhibitors of ACh synthesis
2. Inhibitors of ACh storage
3. Inhibitor of ACh release

Question 23

23. What is Hemicholinium-3?

Answer 23

This is an “inhibitor of ACh synthesis” that blocks the CHT (Na+ - choline transporter into the neuron). By blocking the channel it prevents uptake of choline required for ACh synthesis. This drug is not a therapeutic tool but rather just a research, experimental tool

Question 24

24. What is Vesamicol?

Answer 24

Vesamicol is an ACh storage inhibitor that blocks the ACh-H+ antiporter that is used to transport ACh into vesicles. By blocking the channel it prevents the storage of ACh. This is a research tool and not use therapeutically.

Question 25

25. What is Botulinum toxin?

Answer 25

Botulinum toxin is an inhibitor of acetylcholine release. It is injected locally into muscles for treatment of numerous disease including muscle spasms (Blepharospasm – uncontrollable contraction of eye muscles). It is approved for cosmetic treatment of facial wrinkles.