L11: Cholinergic Pharmacology

Question 1

Cholinergic vs Anticholinergic Drugs

Answer 1

Cholinergic
-Direct acting cholinomimetic drugs: muscarinic agonists, nicotinic agonists
-Indirect acting cholinomimetic drugs

Anticholinergic
-Anti-nicotinic drugs
-Anti-muscarinic drugs

Question 2

Direct acting cholinomimetic drugs

Answer 2

Muscarinic agonists:
-Choline esters: bethanechol
-Alkaloids: pilocarpine

Nicotinic agonists:
-Nicotine

Question 3

Indirect acting cholinomimetic drugs

Answer 3

Cholinesterase- inhibitors

Question 4

Direct acting muscarinic agonists (MOA, clinical use, AE, CI)

Answer 4

PUXG, GUV

MOA:
– Bind to and activate muscarinic (and nicotinic) receptors with different selectivity

Clinical use:
– Postoperative ileus: increasing secretory and motor activity of the gut
– Urinary retention: stimulate the detrusor muscle to contract = voiding
– Xerostomia (dry mouth) due to:
* Sjogren’s syndrome
* Head and neck irradiation
– Glaucoma: contraction of the ciliary/pupillary constrictor muscle facilitates drainage of fluid

Adverse effects:
– General cholinomimetic effects
* GIT: diarrhea, abdominal cramps, nausea/vomiting
* Urinary urgency
* Vision problems

Contraindications:
– Asthma/ COPD
– Urinary or GI tract obstruction

Question 5

Indirect acting cholinomimetic drugs: anti-ChEs (MOA, clinical use, AE, CI)

Answer 5

GATM, MGUV

MOA:
– Blockade of AChE = increase ACh

Clinical uses:
– Glaucoma
– Alzheimer’s disease
– Treatment of mAChR antagonist toxicity
– Myasthenia gravis

Adverse effects:
– General cholinomimetic effects:
* GIT: diarrhea, abdominal cramps, nausea/vomiting
* Urinary urgency
* Vision problems
* Musculoskeletal effects: muscle cramps, myalgia

Contraindications:
– Asthma / COPD
– Urinary or GI tract obstruction

Question 6

Intoxication with anti-ChEs

Answer 6

DUMMBBELLSS

Diarrhea
Urination
Miosis
Muscle weakness, paralysis
Bradycardia
Bronchoconstriction
Excess bronchial secretion
Lacrimation
Lousy for vision
Salivation
Sweating

Cause of death: respiratory failure

Question 7

Antidotes for anti-ChEs intoxication

Answer 7

– Atropine (mAChR antagonist) to control signs of muscarinic excess

– Pralidoxime (AChE reactivator)
* Used for intoxication with organophosphates
* No effect if phosphorylated AChE has “aged”

Question 8

Neuromuscular blockers: Competitive agents (MOA, clinical use, effect on SKM, effect on anti-ChE)

Answer 8

MOA:
- Occupy ACh binding sites on NM receptor, no efficacy

Clinical use:
- Muscle paralysis during surgery

Effect on SKM:
- Flaccid paralysis

Effect on anti-ChE:
- Depolarization of end plate = reversal of block

Question 9

Neuromuscular blockers: Depolarizing Agents (MOA, clinical use, effect on SKM, effect on anti-ChE)

Answer 9

MOA:
- Occupy ACh binding sites on NM receptor, open ion channel, maintains depolarized state of end plate = NaV channels in inactivated state

Clinical use:
- Muscle paralysis during surgery

Effect on SKM:
- Transient fasciculations followed by flaccid paralysis (depolarization blockade)

Effect on anti-ChE:
- Prolongation of depolarized state maintains NaV channels
in an inactivated state→ augmented block

Question 10

Muscarinic antagonists (MOA, use, AE, CI)

Answer 10

MCBRO, DUCTHB

MOA:
– Reversible blockade of muscarinic receptors

Clinical use:
- Motion sickness
- Bradycardia, AV conduction block
- COPD, asthma
- Rhinorrhea
- Overactive bladder, urinary urgency

Adverse effects:
– Dry mouth (Xerostomia)
– High body temperature
– Urinary retention
– Constipation
– Blurred vision
– Tachycardia

Contraindications:
– Urinary and GI obstruction
– Glaucoma

Question 11

Muscarinic antagonists
Toxicity: Atropine intoxication

Answer 11

Dry as a bone
Hot as a stone
Red as a beet
Mad as a hatter
Blind as a bat

Question 12

Antidote for Intoxication with Atropine

Answer 12

– Physostigmine: Reversible inhibitors of AChE = increase ACh = stimulation of muscarinic receptors (tertiary amine structure allows to penetrate BBB)