PARASYMPATHETIC DRUGS

Cholinergic (Parasympathomimetic) Drugs

  • Overview of cholinergic drugs, which mimic the actions of acetylcholine in the parasympathetic nervous system.

Types of Parasympathomimetics

Direct-Acting Cholinoceptor Stimulants (Choline Esters)

  • Esters of Choline:

    1. Acetylcholine

    2. Methacholine

    3. Carbachol

    4. Bethanechol

  • Alkaloids:

    • Muscarinic: Muscarine, Pilocarpine, Oxotremorine

    • Nicotinic: Nicotine, Lobeline, Dimethylphenylpiperazinium (DMPP)

Indirect-Acting Cholinoceptor Stimulants (Anticholinesterases)

  • Reversible Anti-ChE:

    • Carbamates (e.g., Physostigmine, Neostigmine)

    • Bis-quaternary ammonium compounds (e.g., Demacarium)

  • Irreversible Anti-ChE:

    • Organophosphorus compounds (e.g., Tabun, Sarin, Soman - nerve gases; Malathion and Carbaryl - insecticides)

Choline Esters

Chemical Structures

  • Methyl substitution on β-carbon noted; carbamoyl group replaces acetyl in various choline esters.

  • Choline esters completely suitable for pharmacological uses due to their unique properties.

Pharmacologic Actions

Cardiovascular Effects

  • Vasodilation and decreased cardiac rate (-ve chronotropic effect, bradycardia).

  • Decreased conduction in sinoatrial (SA) and atrioventricular (AV) nodes (-ve dromotropic effect).

  • Reduced force of ventricular contraction, leading to decreased cardiac output (CO) and blood pressure (BP).

Gastrointestinal Effects

  • Increased muscle tone and contractions, heightened peristaltic activity, and enhanced GI activity leading to symptoms like nausea and cramping.

Respiratory Effects

  • Bronchoconstriction and increased bronchial secretions.

Ocular Effects

  • Causes miosis (pupil contraction) and accommodation for near vision.

Urinary Tract Effects

  • Increased smooth muscle activity, ureteral peristalsis, detrusor muscle contractions, and decreased bladder capacity leading to increased urinary pressure.

Nervous Control to the Bladder

  • Bladder volume increase leads to activation of stretch receptors → activation of parasympathetic neurons → contraction of detrusor muscle and relaxation of internal urethral sphincter → micturition.

Therapeutic Uses of Choline Esters

Carbachol and Methacholine

  • Less frequently used due to side effects from their significant nicotinic activity.

Bethanechol

  • Utilized for:

    • Gastrointestinal disorders like postoperative distention, gastric atony, adynamic ileus, and congenital megacolon.

    • Urinary retention (%2.5 mg SC, increasing as needed).

Megacolon

Definitions & Types

  • Congenital: Characterized by the absence of myenteric ganglion cells; leads to blockage and abdominal distention.

  • Acquired: Develops after birth; examples include toxic megacolon (inflammatory bowel disease) and iatrogenic (medication-induced).

Glaucoma Treatment with Cholinomimetics

  • Pilocarpine: Used for both chronic open-angle and acute angle-closure glaucoma; acts by contracting ciliary muscle and facilitating aqueous outflow.

  • Mechanism: Targeting M3 receptors enhances trabecular meshwork permeability, lowering intraocular pressure.

Anticholinergic Drugs

Overview and Types

  • Muscarinic receptor antagonists block the action of acetylcholine across various pathways, producing diverse clinical effects.

  • Belladona alkaloids: Atropine and Scopolamine function as antimuscarinic drugs with significant physiologic effects.

  • Adverse Effects: Include elevated heart rate, dry mouth, potential hallucinations, and bronchoconstriction in susceptible patients.

Therapeutic Uses of Anticholinergic Agents

Conditions Treated

  • Peptic ulcer disease, motion sickness, respiratory tract disorders, and excessive salivation.

  • Drugs like Ipratropium bromide specifically treat chronic obstructive airway diseases, minimizing side effects compared to systemic anticholinergics.

Management of Poisoning

  • Atropine serves as the antidote for poisoning due to cholinomimetic agents, including therapeutic use in organophosphate exposure.

Pharmacologic Properties of Drugs

  • Cholinergic Effects: Include increased activity at autonomic effector organs and potently enhanced neurotransmission at neuromuscular junctions.

  • Anticholinesterases: Produce effects that mimic acetylcholine's actions, prolonging its effects due to decreased enzymatic degradation.