Ch. 7 Cholinoceptor-Activating & Cholinesterase-Inhibiting Drugs PART 2

Three Classes of Cholinesterase Inhibitors

Simple alcohols (Edrophonium), Carbamates, Organophosphates

Simple alcohols (Edrophonium),

Reversibly binds AChE without a covalent bond

2–10 minutes

Carbamates

Forms a slowly reversible covalent bond with AChE

30 minutes–6 hours

Neostigmine, pyridostigmine, physostigmine

Organophosphates

Forms a very stable covalent bond with AChE

Very long-lasting, potentially hundreds of hours

(Echothiophate, sarin, parathion, malathion)

Aging

chemical change in the organophosphate–AChE complex that makes the bond even harder to break

AChE inhibitors increase

ACh indirectly by preventing its breakdown

Major Clinical Uses of Cholinergic Drugs

Glaucoma: Improve fluid drainage from the eye.

Urinary retention: Help the bladder contract.

Postoperative ileus: Increase intestinal movement.

Myasthenia gravis (MG): Improve skeletal muscle contraction.

Alzheimer disease: Increase ACh activity in the brain.

Antimuscarinic toxicity: Reverse certain effects of excessive muscarinic receptor blockade

Dry Mouth (Xerostomia)

Muscarinic agonists stimulate salivary gland secretion

Myasthenia Gravis (MG)

AChE inhibitors increase available acetylcholine, allowing remaining nicotinic receptors to be activated more effectively

Lambert-Eaton Myasthenic Syndrome (LEMS)

Treatment: Potassium Channel Blockers

Alzheimer disease

AChE inhibitors increase available ACh and can temporarily improve or stabilize some cognitive symptoms

Excessive muscarinic receptor activation causes

• Increased salivation and sweating.

• Lacrimation (tearing).

• Nausea, vomiting, and diarrhea.

• Urinary urgency.

• Bronchoconstriction.

• Bradycardia.

• Miosis (pupil constriction)

Treatment to excessive muscarinic receptor activation

Atropine, a muscarinic receptor antagonist

Excessive nicotine

can initially stimulate nicotinic receptors, followed by receptor desensitization and blockade

Excessive nicotine toxicity effects

• Hypertension and cardiac arrhythmias.

• Muscle twitching followed by weakness or paralysis.

• Seizures, coma, and respiratory arrest

Nicotine Addiction and Smoking Cessation

Nicotine activates α4β2 nicotinic receptors in the brain, increasing dopamine release and contributing to addiction