Cholinergic Drugs and Their Mechanisms

CHAPTER 20: CHOLINERGIC DRUGS/CHOLINERGIC AGONIST

AUTONOMIC NERVOUS SYSTEM
  • Components:
    • Sympathetic Nervous System
    • Parasympathetic Nervous System (Rest and Digest)
  • Role of Neurotransmitters:
    • Stimulate either fight or flight response or rest and digest response.
  • Key Neurotransmitter for Parasympathetic System:
    • Acetylcholine (ACh)
NEUROTRANSMITTERS & RECEPTOR SITES
  • Acetylcholine Activation:
    • Muscarinic Receptors: M1 - M5
    • Nicotinic Receptors
    • (Including M2, M3, M5)
CHOLINERGIC AGONISTS: DRUG EFFECTS ON THE BODY
  • Body Responses to Cholinergic Drugs are summarized in Table 20.1.
PHARMACOLOGY OF CHOLINERGIC DRUGS
  • Also known as:
    • Parasympathomimetics / Cholinergic Agonists
MECHANISMS OF ACTION: CHOLINERGIC DRUGS

  1. Direct Acting Cholinergic Drugs:

    • Function: Directly stimulate cholinergic receptors by mimicking ACh.
    • Example: Bind to receptor and activate it.

  2. Indirect Acting Cholinergic Drugs:

    • Function: Inhibit acetylcholinesterase (AChE), increasing ACh levels.
    • Result: Prolongs action of ACh at receptor sites.
INDICATIONS FOR CHOLINERGIC DRUGS

  • Direct Acting Cholinergic Drug Indications:

    • Urinary Retention
    • Reduce Intraocular Pressure (used in glaucoma treatment)
    • Sjogren's Syndrome
    • Dry Mouth

  • Indirect Acting Cholinergic Drug Indications:

    • Alzheimer's Disease
    • Myasthenia Gravis
    • Reverse Neuromuscular Blockade
    • Anti-Cholinergic Poisoning
CONTRAINDICATIONS FOR CHOLINERGIC DRUGS
  • Known Drug Allergy
  • GI Obstruction
  • Urinary Obstruction
  • Bradycardia
  • Slow Cardiac Impulse Conduction
  • Hyperthyroidism
  • Epilepsy
  • Hypotension
  • COPD
  • Parkinson's Disease
ADVERSE EFFECTS, TOXICITY & MANAGEMENT OF OVERDOSE

  • Cholinergic Crisis:

    • Late Signs: Circulatory collapse, hypotension, bloody diarrhea, shock, cardiac arrest.
    • Antidote: Atropine.

  • Early Signs:

    • Symptoms: Abdominal cramps, salivation, flushing of the skin, nausea, vomiting, syncope, complete heart block, dyspnea, orthostatic hypotension.
DRUG PROFILES: CHOLINERGIC DRUGS

  • BETHANECHOL:

    • Type: Direct-Acting Cholinergic Agonist
    • Use: Treats acute postoperative and postpartum non-obstructive urinary retention, neurologic bladder atony.
    • Contraindications: Hyperthyroidism, peptic ulcer, active asthma, cardiac disease, epilepsy, Parkinson's.

  • DONEPEZIL (ARICEPT):

    • Type: Indirect Cholinergic Agonist
    • Use: Treats mild to moderate Alzheimer's Disease.
    • Adverse Effects: GI upset (risk of ulcer & bleed), drowsiness, dizziness, insomnia, muscle cramps, complex cardiovascular effects (bradycardia, syncope, hypotension, tachycardia, hypertension).

  • MEMANTINE:

    • Classification: NMDA receptor antagonist, not a cholinergic drug
    • Role: Treatment for Alzheimer’s dementia, blocks NMDA receptor stimulation.

  • PYRIDOSTIGMINE:

    • Type: Indirect Acting Cholinergic Agonist
    • Use: Improves muscle strength in myasthenia gravis and reverses nondepolarizing neuromuscular blockade.
    • Contraindications: Prior severe cholinergic reactions, asthma, gangrene, hyperthyroidism, cardiovascular disease, mechanical GI/GU obstructions.
    • Adverse Effects: GI upset, excessive salivation.