Cholinergic Drugs made Simple

Cholinergic drugs promote the action of the neurotransmitter acetylcholine. These drugs are also called parasympathomimetic drugs because they produce effects that imitate parasympathetic nerve stimulation.

Cholinergic receptors and their Sites

Muscarinic

1. M1: Stomach, Ganglion, CNS
2. M2: Heart, Lung, Stomach, Bladder, Penis
3. M3: Eye, Glands, Endothelium

Nicotinic (N): Skeletal muscle, Ganglion, CNS

Actions and Adverse Drug reactions (ADRs) of Cholinergic Drugs:

Remember the mnemonics “DUMB HAVES”

1. Defecation (Increased GI motility)
• ADR: Cramps and diarrhea
2. Urination (Detrusor contraction and Sphincter relaxation)
• ADR: Urinary frequency
3. Muscle (Skeletal) excitation
• ADR: Twitchings and fasciculations
4. Bronchospasm
• ADR: Shortness of breathe (Dyspnea)
5. Heart bradycardia and reduced contractility, conductivity
• ADR: Bradycardia
6. Autonomic ganglia stimulation
7. Vascular dilation (hypotenstion and erection)
• ADR: Hypotension
8. Eye miosis and accomodation spasm
• ADR: Blurred vision
9. Secretions increase (lacrimation, sweating, salivation, GI secretions)
• ADR: Nausea, vomiting, increased sweating and salivation
10. Stimulation followed by depression in CNS
• ADR: Delirium

Classification:

1. Directly acting: Cholinergic agonists (Cholinomimetics)
2. Indirectly acting: Cholinesterase inhibitors (Anticholinesterases)

CHOLINOMIMETICS

Cholinomimetics stimulate the cholinergic receptors mimicking acetylcholine. The drugs falling under this category can be remembered using a mnemonic “ABC MNoP” :

1. Arecoline (M1, M2, M3, N)
2. Bethanechol (M1, M2, M3, N)
3. Carbachol (M1, M2, M3, N)
4. Methacholine (M1, M2, M3, N)
5. Nicotine (N)
6. Pilocarpine (M1, M2, M3)

Route of administration:

1. Oral, subcutaneous: Bethanechol
2. Topical: Carbachol, Pilocarpine
3. No i.m or i.v due to 2 reasons:
• immediate metabolism by cholinesterase
• rapid action leading to cholinergic crisis (muscle weakness and paralyasis of respiratory muscles)

Therapeutic uses:

1. Atonic bladder and Urinary retention and Postoperative Gastrointestinal atony (Bethanechol)
2. Glaucoma and eye surgery (Pilocarpine and Carbachol)
3. Xerostomia (Pilocarpine)
4. Challenge test for diagnosis of asthma (Methacholine)
5. Smoking cessation aid (Nicotine)

Now let us move on to the Anticholinesterases

ANTICHOLINESTERASES

Anticholinesterases inhibit the enzyme acetylcholinesterase that breaks acetylcholine and thus builds up more acetylcholine at the synapse to act on the cholinergic receptors. The drugs are:

1. Reversible (Minutes to Hours action): Carbamates carbamylate (reversibly inhibit) cholinesterase
• Mnemonic: ADD EGG PRiNT
• Ambenonium
• Demecarium
• Donepezil
• Edrophonium
• Galantamine
• Guanidine
• Physostigmine
• Pyridostigmine
• Rivastigmine
• Neostigmine
• Tacrine
2. Irreversible (Days to Weeks action): Organophosphates phosphorylate (irreversibly inhibit) cholinesterase
• Organophosphates
• Echothiophate
• Parathion
• Malathion

Route of administration:

1. Topical Eye drops (Glaucoma): Physostigmine, Demecarium, Ecothiophate
2. Oral: Neostigmine, Pyridostigmine, Ambenonium
3. I.m/I.v: Physostigmine, Neostigmine, Edrophonium, Pyridostigmine

Distibution:

1. Physostigmine is Fat (Phyat) Soluble and hence crosses blood brain barrier and hence used to reverse toxic effects due to anticholinergic drugs like atropine.
2. Neostigmine is water soluble and cannot cross BBB but is highlt concentrated in the Neuromuscular junction and hence used in treatment of Myasthenia gravis.

Therapeutic uses:

1. Gastrointestinal atony and urinary retention (Neostigmine)
2. Reversal of Neuromuscular blockade (Neostigmine)
3. Myasthenia gravis (Neostigmine, Pyridostigmine)
4. Differentiating Cholinergic and Myasthenic crisis (Edrophonium)
5. Glaucoma (Physostigmine, Demecarium, Ecothiphate)
6. Alzheimer’s disease (Physostigmine, Tacrine)
7. Atropine overdose/Belladona poisoning (Physostigmine)

To be used cautiously in:

1. Peptic ulcer
2. Asthma and COPD
3. Seizure patients
4. Mechanical bladder obstruction

Anticholinesterase or Organophosphate poisoning

1. Symptoms (DUMBBELSS): Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Excitation of skeletal muscle and CNS, Lacrimation, Sweating, Salivation
2. Antidote: Atropine (Muscarinic antagonist) + Pralidoxime (Chemical antagonist used to regenerate active cholinesterase)