Parasympathetic Nervous System Overview

Parasympathetic Nervous System

• Often described as the "Feed and Breed" or "Rest and Digest" portion of the autonomic nervous system (ANS).
• Maintains essential body functions, like digestion and waste elimination.
• Acts to oppose or balance the actions of the sympathetic division.

Parasympathetic Neurotransmitters and Receptors

• Acetylcholine (ACh) is the primary neurotransmitter.
• ACh stimulates muscarinic receptors.
• Parasympathomimetics (also called cholinomimetic drugs) stimulate muscarinic receptors.

Parasympathomimetic Classification

• Direct Acting:

  • Choline esters: Natural (acetylcholine), synthetic (methacholine, carbachol, bethanechol)
  • Natural alkaloids: Pilocarpine.

• Indirect Acting (Anticholinesterases):

  • Reversible: Edrophonium (rapidly acting), neostigmine, physostigmine, pyridostigmine (slowly acting).
  • Irreversible: Insecticides (parathion, malathion), war gases (soman, tabun), Anti-bilharzial (metrifonate), Anti-Glaucoma (echothiophate).

Acetylcholine Function

• Postganglionic neurotransmitter in the parasympathetic nervous system.
• Preganglionic neurotransmitter for both sympathetic and parasympathetic systems.
• Neurotransmitter at non-autonomic sites (e.g., stimulating skeletal muscle, brain/spinal cord).

Cholinergic Transmission

• Synthesis, release, and degradation of ACh are crucial.

Pharmacokinetics of Parasympathomimetics

• Many are not absorbed orally (ionized quaternary ammonium compounds).
• Do not pass the blood-brain barrier.
• Broken down by cholinesterase enzymes.

Pharmacological Actions (Parasympathomimetics)

• Muscarinic Actions:

  • Eye: Miosis (pupil constriction), accommodation for near vision, increased lacrimation, decreased intraocular pressure (IOP).
  • Cardiovascular System (CVS): Decreased heart rate and conduction, vasodilation, hypotension.
  • Gastrointestinal (GIT) System: Increased motility and tone, increased secretions.
  • Bronchi: Bronchoconstriction.
  • Exocrine Glands: Increased secretions (salivary, sweat, lacrimal, etc.)
  • Uterus: Increased contraction (non-pregnant).

• Nicotinic Actions:

  • Autonomic ganglia and adrenal medulla: Increased response, hypertension possible.
  • Motor end plate: Skeletal muscle twitches.

Natural Alkaloids (e.g., Pilocarpine)

• Excreted unchanged in the urine
• Not hydrolyzed by cholinesterases.
• Primarily direct muscarinic effects.
• Functions include increased secretions (sweat, saliva) miosis, Increased contractility of bronchi, intestines, and urinary bladder.

Anticholinesterases

• Reversible: Compete with acetylcholine (Ach) at binding sites, block inactivation temporarily; hydrolyzed more slowly
• Irreversible: Form very stable complexes with cholinesterases; permanently inhibit enzyme activity; potentially toxic.

Treatment of Organophosphorus Poisoning

• Endotracheal intubation, artificial respiration
• Avoid further exposure, decontamination procedures (washing)
• Atropine administration (mucarinic blocking)
• Cholinesterase reactivators (e.g., oximes)
• Anticonvulsants (e.g., diazepam)

Parasympathetic Antagonists (Anticholinergics)

• Antimuscarinics: Primarily block muscarinic actions of acetylcholine.
• Ganglionic Blocking Agents: Block parasympathetic and sympathetic neurotransmission at ganglia.
• Neuromuscular Blocking Agents: Block neuromuscular junction.

Parasympathetic Antagonist Examples

• Atropine: Prototype. Blocks muscarinic receptors, and is widely used as pre-anesthetic medication, and in the treatment of various conditions.
• Scopolamine: Similar to atropine but has greater CNS effects.

Scopolamine

• Differences from atropine:
• More CNS depressant effects (sedation, amnesia, anti-motion sickness).