Cholinergic Agonist/Antagonists Flashcards by Reagan Mahoney

Acetylcholine

Coline Ester

*Muscarinic and nicotinic agonist

Use: obtain miosis after delivery of the lens in cataract Sx

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Metacholine

Choline Ester

Muscarinic Agonist

Use: Dx of bronchial airway hyperactivity in subjects who do not have clinically apparent asthma

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Bethanechol

Choline Ester

Muscarnic agonist

Use: Post-OP urinary retention, and atony of the urinary bladder

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Carbachol

Choline Ester

Muscarnic and nictotinic agonist
Uses:
1. Miosis during surgery
2. Reduce intraocular pressure after cataract Sx

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Pilocarpine

Natural Alkaloids

Partial muscarnic agonist
Tertiary amine
Stable to hydrolysis by AChE

Use:
1. Second line of open angle glaucoma
2. Management of acute angle-closure glaucoma
3. Tx of dry mouth by radiotherapy or Sjogren’s Syndrome

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Nicotine

Natural Alkaloids

Selective Nicotinic Agonist
Tertiary amine

Action:
Low dose: ganglionic stimulation-resembles simultaneous para/sympathetic nervous system

High dose: ganglionic blockade and neuromuscular blockade

Uses: Smoking Cessation Therapy

Can depolarize autonomic ganglia-resulting first in stimulation and then paralysis

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Edrophonium

Anticholinesterase

binds reversilby to the active site of the enzyme (no covalent bond)
-inhibition is short lived

Uses:
1. To Dx myasthenia gravis-leads to rapid increase in muscle strength.
2. Reverse neuromuscular blocks produced by non-depolarizing muscular blockers

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What is the effect on the CVS of Anticholinesterases?

Minimal-due to vascular beds that lack cholinergic innervation

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Physostigmine

Anticholinesterase

Tertiary amine (can enter and stimulate CNS)

Uses: Tx of overdoses of anticholinergic drugs

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Neostigmine

Anticholinesterase

Quaternary ammonium

Uses:
1. Post-Op Urinary retention
2. Reversal of effects of non-depolarizing neuromuscular blockers after surgery
3. Tx of myasthenia gravis

Off label use of Tx of non-obstructive ileus

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Pyridostigmine

Anticholinesterase

Quaternary Ammonium-does not enter CNS

Uses: Myasthenia Gravis treatment

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Echothiophate

Organophosphate

Rarely used for glaucoma

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What are the 3 acetylcholinesterase inhibitors used in the treatment of ALzheimer’s Disease?

Donepezil
Rivastigmine
Galantamine

Tertiary amines–> cross BBB

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What are the two natural Alkaloids?

Atropine
Scopolamine

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Atropine action

Muscarinic Receptor Antagonists: Belladone Alkaloids

**Reversible competitive antagonist **
Tertiary amine: both central and peripheral muscarinic blocker

Action: M3 blockade
Eye: Mydriasis & cycloplegia
GI: reduce gastric motility
Urinary: decrease hypermotility of urinary bladder
Secrections: block (sweat, salivary…)
M2 blockade: moderate to high doses cause tachycardia

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What are the 3 uses for Atropine?

Antidote for cholinergic agonists (organophosphate poisoning)
Block respiratory secretions prior to surgery
Antispasmodic: relax GI tract/bladder

What are the adverse effects of Atropine?

Dry mouth, tachy, blurred vision, constipation, tachycardia, urinary retention, sandy eyes

CNS effects: restlessness, confusion, hallucinations, delirium-similar to hallucinigens

Pralidoxime

Reactivator of AChE

Split phosphorous-enzyme bond

Adjunct therapy in organophosphate poisoning

Scopolamine uses and mechanism of action

Belladona Alkaloid

Used to treat motion sickness-enters vomiting center (M1), mydriasis and cycloplegia in diagnositc procedures
* Tertiary amine
* Blocks short-term memory
* Longer duration of action compared to atropine

Produces sedation in contrast to atropine

Ipratropium/Tiotropium

Quaternary Ammonium Muscarinic Antagonist

Uses: Tx of COPD, Asthma
Bronchodilator

Tropicamide, Cyclopentolate, Homatropine

Tertiary Amine Muscarinic Antagonist

Uses: Mydriatics for fundoscopy
Produce mydriases w/ cycloplegia

Short half life compared to atropine (preferred)

Glycopyrrolate

Quaternary ammonium compound

Uses:
1. Prevention of bradycardia in Sx
2. COPD
3. Adjunctive therapy of peptic ulcer
4. Severe drooling in neuro cases

Contraindications of Antimuscarinic Agents? (2)

Angle-closue glaucoma
BPH/elderly patients

Elderly are very sensitive to cholinergic blockade-causes acute encephalopathy, falls, urinary retention, exacerbation of functional/behavior/cognitive deficits

Benztropine, Trihexyphenidyl

Treatment only

Treatment of Parkinson’s Disease and Extrapyramidal Symptoms associated w/ antipsychotic meds

Tertiary Amine Muscarinic Antagonist

Oxybutynin, Tolterodine | Treatment only

**Overactive bladder** Tertiary amine | Muscarinic Antagonist

Hexamethonium | Ganglion Blocker

Previously used for HTN but d/t A/E replaced by other anti HTN Pharm properties: **remove dominant control** of the ANS

Tubocurarine | Competitive Antagonist (Non-depolarizing blocker)

Uses: adjuvant drugs in anaesthesia during surgery to relax skeletal muscle

Name the 5 Non-depolarizing NMJ blockers

1. Tubocurarine-prototype 2. Pancuronium 3. Rocuronium 4. Vecuronium 5. Mivacurium-short acting (hydrolysis by plasma **butyrylcholinestrase**

What is the action of NMJ non depolarizing blockers?

First cause motor weakness-->skeletal muscles become totally flaccid and inexcitable to stimulation Action can be overcome by increasing concentration of ACh-**Edrophonium** and **Neostigmine**

Succinylcholine | Agonist (Depolarizing Blocker)

Uses: Endotracheal intubation ECT Rapid blockade (<1 min onset, lasts 5 min) **Fasciculations** Not metabolized by AChE leading to flaccid paralysis

What happens to patients with low-activity geneetic polymorphism of the enzyme butyrlcholinesterase?

Longer time to metabolise Succinylcholine-mechanical ventilation until muscle function returns to normal

What are the adverse effects of Succinylcholine? | (4)

1. Muscle pain 2. **Hyperkalemia**-loss of tissue potassium d/t depolarizaqtion 3. Increased intraocular pressure 4. **Malignant hyperthermia**-excessive release of Ca2+ from SR. Defect in Ryanidine Receptor gene (RYR1)

Treatment for Malignant Hyperthermia?

Dantrolene

Inhibitor of ACh Release

Botulinum Toxin Uses: 1. Cosmetic Tx of facial wrinkles 2. Severe muscle spasms (Ex: Blepharospasm-inability to open eyes) | Acts presynaptically

Inhibitor of ACh Synthesis

Hemicholinium-3 Prevents uptake of choline to make ACh Research tool

Inhibitor of ACh Storage

Vesamicol Blocks ACh-H+ antiporter using transport ACh into vesicles Research tool

Mecamylamine

Ganglion Blocker used as an **antihypertensive** agent

General properties of Neuromuscular blockers (4)

1. Block at Nm receptor on skeletal muscle 2. Highly polar-poorly soluble in lipid 3. Do not cross BBB or enter cells 4. **Always given IV/IM**-inactivated if given PO