Pharmacology for Midwifery: ANS Drugs

Pharmacology for Midwifery

• This is a pharmacology course for midwives.

Drugs Affecting the Autonomic Nervous System (ANS)

• The autonomic nervous system (ANS) controls involuntary body functions.
• It has two divisions:
  • Sympathetic (fight-or-flight)
  • Parasympathetic (rest-and-repose)
• ANS pathways use preganglionic and postganglionic fibers.
• The target tissue is called an effector.
• Key neurotransmitters are acetylcholine and noradrenaline.
  • Cholinergic fibers release acetylcholine, and their receptors are cholinergic.
  • Adrenergic fibers release noradrenaline, and their receptors are adrenergic
• Neuromodulators can alter nerve and tissue responses.

Cholinergic Division

• Two main subtypes of cholinergic receptors:

  • Nicotinic receptors: respond to nicotine
  • Muscarinic receptors: respond to muscarine

• Both receptor types are activated by acetylcholine, but have structural differences.

Nicotinic Receptors

• Located in autonomic ganglia and neuromuscular junctions of skeletal muscles.
• Effects of stimulation include:
  • Behavioral changes (relaxation, well-being)
  • Increased autonomic tone (both sympathetic and parasympathetic)
  • Adrenaline and noradrenaline release from the adrenal medulla
  • Increased skeletal muscle tone

Common Adverse Effects (Nicotine)

• At doses absorbed during smoking, nicotine is a peripheral stimulant (mostly cardiovascular).
• Nicotine treatment for quitting mimics these effects.
• Potential adverse effects: cardiovascular stimulation, headaches, nausea, insomnia, skin reactions (itching, burning, redness).
• Contraindications: pregnancy, lactation, hypersensitivity, serious cardiovascular conditions (e.g., acute MI, unstable angina, recent stroke, dysrhythmia).

Muscarinic Receptors

• Located centrally and peripherally on effectors stimulated by cholinergic nerves (most parasympathetic and some sympathetic).
• Located on various peripheral tissues, including iris, sweat glands, lacrimal glands, digestive glands, myocardium, bronchioles, gastrointestinal tract, urinary tract, liver, sex organs, blood vessels (skin, genitalia, and skeletal muscle).

Mechanism of Action (Muscarinic Receptors)

• Five distinct functional subtypes (M1, M2, M3, M4, M5).
• M1 and M3 receptors are primarily located within the brain and mediate higher brain functions; reduction in receptor numbers within the cortex has been linked to Alzheimer's disease.
• M1 receptors are also located peripherally (stomach) and stimulate acid secretion.
• M2 receptors are in the myocardium and reduce heart rate and contraction strength when stimulated.
• M3 receptors are associated with visceral smooth muscle and exocrine glands
• Stimulate various parasympathetic responses, including pupil constriction, increased GI motility and secretion, increased bronchial mucus secretion etc

Common Adverse Effects (Muscarinic Receptors)

• Common adverse effects include bradycardia, hypotension, pupil constriction, sweating, bronchoconstriction, drooling, diarrhea.
• Contraindications include intestinal and urinary obstruction.

Cholinergic Agonists (Direct Acting)

• Include acetylcholine, bethanechol, carbachol, and pilocarpine
• Stimulate acetylcholine release

Cholinergic Agonists (Indirect Acting)

• Example: Cisapride
• Stimulates acetylcholine release from myenteric plexus.

Anticholinesterases (Mechanism of Action)

• Inhibit acetylcholine metabolism (cholinesterase)
• Prolong the action of acetylcholine

Common Adverse Effects (Anticholinesterases)

• Common adverse effects: pupil constriction, hypotension, bradycardia, diarrhea, muscle twitching, bronchoconstriction, increased lacrimation, sweating.

Anticholinesterases (Drugs)

• Donepezil, galantamine, pyridostigmine, neostigmine, physostigmine.
• Edrophonium (very short-acting).
• Use in reversal of neuromuscular blockers (with atropine or propantheline to minimize muscarinic effects)

Myasthenia Gravis (Considerations)

• Medications for myasthenia gravis should be taken early in the day.
• Overdose on anticholinesterase can lead to a cholinergic crisis.
  • Excessive sweating, defecation, urination, miosis, salivation, bradycardia, muscle weakness.

Nicotinic Antagonists

• Used as ganglionic and neuromuscular blocking agents.
• Used in surgery, blood pressure issues, trauma cases

Depolarizing Neuromuscular Blocking Agents (e.g., Succinylcholine)

• Acts as an acetylcholine agonist at nicotinic receptors.
• Action is sustained, preventing repolarization and leading to paralysis.
• Causes muscle fasciculations which are immediately followed by flaccidity,

Non-Depolarizing Neuromuscular Blocking Agents (e.g., Atracurium)

• Antagonistic towards acetylcholine
• Block receptors to cause complete paralysis without fasciculation
• Reversed by giving acetylcholine increasing agents (eg. neostigmine)

Muscarinic Antagonists

• Block muscarinic receptors.
• Also known as anticholinergic drugs/ antimuscarinic drugs.
• Include atropine, hyoscine, scopolamine, glycopyrrolate, ipratropium, etc
• Common adverse effects include blurred vision, dry mouth, constipation, blurred vision, and tachycardia

Uses of Muscarinic Antagonists

• Antispasmodics (treating spasms)
• Antiulcerants (reducing gastric acid secretion)
• Antiemetics
• Antidysrhythmics
• Mydriatics and cycloplegics
• Premedication for anesthesia
• Bronchodilators
• Treatment for urinary frequency, enuresis, and incontinence.