Cholinergic Drugs: Agonists, Antagonists, and Clinical Uses

1. Cholinergic Agonists

Respond to acetylcholine; refers to receptor sites stimulated by acetylcholine, as well as neurons that release acetylcholine.

• Cause SLUDGE: Salivation, Lacrimation, Urination, Defecation, Gastrointestinal distress, Emesis

2. Direct-Acting Cholinergic Agonists

1. Acetylcholine (Both Muscarinic and Nicotinic)
   • Miosis (pupil constriction)
   • Limited clinical use due to:
     • Non-selectivity
     • Charged nature
     • Short half-life
2. Bethanechol (Muscarinic)
   • Clinical use: Urinary retention
   • Side effect: SLUDGE
   • Not hydrolyzed
3. Pilocarpine (Muscarinic)
   • Clinical use: Dry mouth, Glaucoma
   • Side effect: SLUDGE
   • Can cross the blood-brain barrier (BBB)
4. Succinylcholine (Muscarinic)
5. Carbachol (Both Muscarinic and Nicotinic)
   • Not hydrolyzed
6. Nicotine (Nicotinic)
   • Clinical use: Smoking cessation aid
7. Methacholine (Muscarinic)
   • Test for asthma
   • Slow hydrolysis
8. Muscarine (Muscarinic)
   • Poison; natural product
9. Varenicline (Nicotinic)
   • Clinical use: Smoking cessation aid

3. Indirect-Acting Cholinergic Agonists (Reversible)

Carbamates: Harder to hydrolyze than esters

1. Neostigmine (Quaternary Amine)
   • Half-life: 0.5-4 hours
   • Treats myasthenia gravis
2. Pyridostigmine (Tertiary Amine)
   • Half-life: 4-6 hours
   • Treats myasthenia gravis (muscle weakness) - maintenance therapy
   • Does not cross the BBB
   • Treats sarin exposure
3. Physostigmine (Quaternary Amine)
   • Half-life: 0.5-2 hours
   • Reverses anticholinergic effects
   • Natural product

Alzheimer's Disease

1. Rivastigmine

Edrophonium

• Diagnoses myasthenia gravis (Tensilon test)
• Antagonist to reverse neuromuscular block

4. Indirect-Acting Cholinergic Agonists (Irreversible)

1. Echothiophate
   • Treats glaucoma (damages the optic nerve)

5. Cholinergic Antagonists

Anti-SLUDGE

6. Antimuscarinic Agents

Tertiary Amine

1. Atropine (Muscarinic)
   • Pre-anesthetic medication
   • Used in heart studies, including during anesthesia
   • Causes dilated pupils (mydriasis)
2. Scopolamine (Muscarinic)
   • Stops motion sickness

Quaternary Amine

1. Ipratropium
   • Treats asthma and chronic obstructive pulmonary disease (COPD)

7. Neuromuscular Blocking Agents

Non-Depolarizing

1. Pancuronium
   • No histamine release
   • Similar to tubocurarine
2. Tubocurarine
   • Paralysis; pre-surgery drug
   • Slow onset; long duration
   • Significant side effect: histamine release
3. Rocuronium
   • Reduces respiratory activity
   • Fast onset; fast duration

Depolarizing

1. Succinylcholine
   • Anesthetic
   • Side effect: hyperkalemia
   • Slow hydrolysis

8. Spasmolytics

1. Dantrolene
   • Relaxes muscle spasms
   • Blocks release of Ca2+
   • Treats hyperthermia

9. Ganglionic Blocking Agents

Stimulants

1. Nicotine
   • Stimulates ganglia

Blocking Agents

1. Trimethaphan
   • Causes vasodilation & hypotension
   • Treats hypertension; anesthetic
2. Hexamethonium
   • Treats hyperthermia