Lectures 13 - 14: Cholinergic System 1 and 2

Question 1

Treatment of anticholinesterase overdoses.

Answer 1

Atropine

Question 2

Can cause prolonged/excessive skeletal muscle paralysis

Answer 2

Gentamycin (aka aminoglycosides)

Question 3

Treatment of Parkinson’s disease and tardive dyskinesia.

Answer 3

Benztropine

Question 4

Block of choline uptake

Answer 4

Hemicholinium

Question 5

Is also an antiemetic.

Answer 5

Scopolamine (Hyoscine)

Question 6

Oxime Compounds (cholinesterase re-activators)

Answer 6

Pralidoxime

Question 7

Antispasmodic: relax GI tract and bladder.

Answer 7

Atropine

Question 8

Direct acting cholinergic agonists

Answer 8

Pilocarpine

Question 9

High dose: excitation effect such as restlessness, disorientation and hallucinations.

Answer 9

Atropine

Question 10

Actions of Muscarinic Antagonists (atropine, Benztropine, Ipratropium, Scopolamine (Hyoscine))

Answer 10

-Peripheral
● Block secretions (saliva, bronchial, GIT, etc.).
● Dilates pupil (mydriasis).
● Mydriasis can precipitate narrow angle glaucoma in the predisposed.
● Relaxes ciliary muscle to cause cycloplegia (lens fixed for far vision).
● Tachycardia (block of vagal influence).
● Blocks GIT motility (constipation).
● Relaxes bronchial smooth muscles.

Question 11

Choline esters (longer duration than Ach)

Answer 11

Bethanechol

Question 12

Blocks the rate-limiting step (uptake of choline into the neuron)

Answer 12

Hemicholinium

Question 13

Muscarinic antagonists (no action on nicotinic receptors)

Answer 13

Atropine

Question 14

Blocks nicotinic receptors on skeletal muscles

Answer 14

Gentamycin (aka aminoglycosides)

Question 15

Antisecretory: block secretions in the upper and lower respiratory tracts prior to surgery.

Answer 15

Atropine

Question 16

Long-acting reversible anticholinesterases

Answer 16

Neostigmine, Physostigmine

Question 17

Block of Ach storage

Answer 17

Vesamicol

Question 18

Induce reactivation of enzymes inactivated by phosphorylation.

Answer 18

Pralidoxime

Question 19

Adverse Effects of Muscarinic Agonists (Acetylcholine, Pilocarpine, Bethanechol)

Answer 19

-Hypotension:
● Due to vasodilation :
Caused by the muscarinic receptor mediated release of NO from endothelium.
● Also due to decreased cardiac output:
due to decreased heart rate and force of contraction.
● Reflex tachycardia often overrides bradycardia.
-Bronchospasm:
● No significance in normal individuals, but may precipitate asthma in asthmatics.
-Others:
● Nausea, vomiting, GIT cramps, and diarrhea.

Question 20

Actions of Acetylcholine

Answer 20

-Heart: decreases heart rate and cardiac output.
-Blood vessels: vasodilation and decrease in blood
pressure.
-GI tract: increases salivary secretion and stimulates
intestinal secretion and motility.
-Lungs: enhanced bronchiolar secretions and
bronchoconstriction.
-Genitourinary tract: increased tone of the detrusor
urinae muscle causing the expulsion of urine.
-Eye: muscle contraction for near vision and pupil
constriction (miosis).

Question 21

Irreversible (Long-acting) Anticholinesterases:
Organophosphates
War gases and pesticides.

Answer 21

Ecothiophate

Question 22

Treatment of paralytic ileus and bladder atony

Answer 22

Neostigmine

Question 23

Block Ach release

Answer 23

Botulinum toxin

Question 24

Eye: persistent mydriasis

Answer 24

Atropine

Question 25

Muscarinic Antagonists

Answer 25

Ipratropium, Scopolamine (Hyoscine)

Question 26

Increase Ach release

Answer 26

Latrotoxin

Question 27

Therapeutic uses of Scopolamine (Hyoscine)

Answer 27

- Treatment of motion sickness. | - Blocking short term memory and is used as an adjunct with anesthesia.

Question 28

Block of post-synaptic Ach receptors

Answer 28

Atropine

Question 29

Has no CNS effect at low doses.

Answer 29

Atropine

Question 30

Treatment of Alzheimer’s disease

Answer 30

Physostigmine

Question 31

Toxicity of Anticholinesterases (common with organophosphates) (Ecothiophate, Neostigmine, Physostigmine):

Answer 31

-Acute ● Vomiting, colic and diarrhea. ● Constricted pupils that are unresponsive to light. ● Sweating and salivation. ● Bronchoconstriction. ● Bradycardia ● Agitation, confusion and respiratory depression. (Especially, physostigmine and organophosphates) -Chronic ● Demyelination: sensory loss and respiratory paralysis

Question 32

Treatment of GIT cramps.

Answer 32

Scopolamine (Hyoscine)

Question 33

Treatment of Organophosphate Poisoning

Answer 33

Pralidoxime

Question 34

Anticholinesterases (Indirect-acting cholinergic agonists)

Answer 34

Ecothiophate, Neostigmine, Physostigmine

Question 35

Naturally occurring alkaloids (longer duration than Ach)

Answer 35

Pilocarpine

Question 36

Treatment of asthma and chronic bronchitis.

Answer 36

Ipratropium

Question 37

Greater action on the CNS than atropine and a longer duration of action.

Answer 37

Scopolamine (Hyoscine)

Question 38

Plant product

Answer 38

Scopolamine (Hyoscine)

Question 39

Treatment of myasthenia gravis

Answer 39

Neostigmine

Question 40

Contraindications of Muscarinic Agonists (Acetylcholine, Pilocarpine, Bethanechol)

Answer 40

- Coronary insufficiency (worsened by hypotension). - Hyperthyroidism (may precipitate atrial arrhythmias). - Peptic ulcer. - Asthma.

Question 41

Used for glaucoma

Answer 41

Pilocarpine

Question 42

Treatment of atropine poisoning

Answer 42

Physostigmine

Question 43

Direct acting cholinergic agonists

Answer 43

Bethanechol

Question 44

Treatment of glaucoma

Answer 44

Ecothiophate, Physostigmine

Question 45

Selective muscarinic receptors

Answer 45

Pilocarpine, Bethanechol

Question 46

Adverse Effects of Muscarinic Antagonists (Atropine, Benztropine, Ipratropium, Scopolamine (Hyoscine) )

Answer 46

- Urinary retention. - Dry mouth. - Blurred vision. - Tachycardia. - Constipation. - Confusion. - Myadriasis - contraindicated in people who are predisposed to glaucoma.

Question 47

Used for paralytic ileus and urinary retention

Answer 47

Bethanechol

Question 48

Reversal of competitive neuromuscular block

Answer 48

Neostigmine

Question 49

Is a depressant at therapeutic dose. | -Sedation, drowsiness, and amnesia.

Answer 49

Scopolamine (Hyoscine)

Question 50

Effects of Anticholinesterases (Ecothiophate, Neostigmine, Physostigmine)

Answer 50

``` -Peripheral ● Enhanced neuromuscular transmission. ● Increased GIT motility/bladder contraction. ● Bradycardia. ● Pupil constriction. ● Bronchoconstriction. -Central ● General CNS stimulation (agitation and convulsion) followed by respiratory depression (death). ```

Question 51

Useful in Parkinsonism

Answer 51

Benztropine

Question 52

Can cause prolonged/excessive skeletal muscle paralysis

Answer 52

Gentamycin (aka aminoglycosides)

Question 53

Found in spider venom

Answer 53

Latrotoxin

Question 54

Alkaloid found in Atropa belladonna

Answer 54

Atropine

Question 55

Quaternary nitrogen compound

Answer 55

Ipratropium

Question 56

Clinical Uses of Muscarinic Antagonists | Atropine, Scopolamine (Hyoscine)

Answer 56

- Surgery: as pre-anesthetic to inhibit salivary and bronchial secretions. - Antidote: in treatment of anticholinesterase poisoning. - Treatment of GIT cramps. - Treatment of Parkinson’s disease and tardive dyskinesia. - Treatment of sinus bradycardia after MI.