Drugs and the PNS

Page 1: Overview of Nervous System and Drug Actions

  • Nervous System Components

    • Sensory Division

      1. Somatic senses

      2. Special senses

    • Motor Division

      1. Somatic Nervous System (SNS)

      2. Autonomic Nervous System (ANS)

  • Lecture Outline

    • Part 1: Drugs and the Autonomic Nervous System

      • A. Drugs and Parasympathetic Nerves

      • B. Drugs and Sympathetic Nerves

      • C. Drugs at ganglia of autonomic nerves

    • Part 2: Drugs and Somatic Motor Activity

  • Key Drug Actions

    • Agonist: Binds and activates the receptor (mimics endogenous mediator)

    • Antagonist: Binds but does not activate (opposes endogenous mediator)

Page 2: Drugs and Autonomic Nervous System

  • Part A: Drugs affecting Parasympathetic Nerves

  • Part B: Drugs affecting Sympathetic Nerves

    • ACh is crucial for parasympathetic effects (muscarinic receptors)

    • Noradrenaline (NA) is key for sympathetic effects (nicotinic receptors)

  • ACh release at both sympathetic and parasympathetic ganglia involves nicotinic receptors

Page 3: Acetylcholine Receptors

  • Subtypes of Acetylcholine Receptors (Cholinoceptors)

    • Muscarinic Receptors: M1, M2, M3, M4, M5

    • Gq and Gi Protein Coupling

      • Gq: Activates phospholipase C (PLC), affects calcium release

      • Gi: Inhibits adenyl cyclase, reduces cAMP levels

  • Clinical Implications

    • Variations in receptor subtypes lead to different physiological effects

    • Example: Bronchoconstriction from muscarinic receptor activation

Page 4: Nervous System Target Effects

  • Target Organs and Effects

    • Respiratory System:

      • Sympathetic: Bronchodilation

      • Parasympathetic: Bronchoconstriction

    • Eye:

      • Sympathetic: Dilation (radial muscle)

      • Parasympathetic: Constriction (circular muscle)

    • Cardiovascular System:

      • Sympathetic: Increased heart rate

      • Parasympathetic: Decreased rate

Page 5: Muscarinic Receptor Effects

  • Components Affected and Agonist/Antenagonist Effects

    • Respiratory: M3 receptor action leads to contraction

    • Digestive System: M3 effects lead to increased motility and secretion

    • Cardiovascular: M2 receptor agonists reduce rate, antagonists increase it

    • Autonomic Tone:

      • Sympathetic: Predominates in stress

      • Parasympathetic: Active during rest

Page 6: Clinically Useful Muscarinic Agonists

  • Bethanechol: Used for bladder/GI dysfunction (underactivity)

  • Pilocarpine: Used for glaucoma, induces pupil contraction

Page 7: Muscarinic Antagonists

  • Atropine: Treats bradycardia and gastrointestinal hyperactivity

  • Oxybutynin: Used for urinary incontinence

  • Ipratropium: Relaxes bronchi for treating asthma by reducing parasympathetic activity

Page 8: Adrenoceptor subtypes

  • Adrenoceptors types and activation pathways

  • Effects on Organ Systems:

    • Activation leads to various sympathetic responses (stimulation/inhibition)

Page 9: Target Effects of Sympathetic Nervous System

  • Effects of adrenergic stimulation on:

    • Respiratory System: β2 receptors cause bronchodilation

    • Digestive System: β2 reduces motility/secretion

    • Cardiovascular System: β1 and β2 increase heart rate and force

Page 10: Clinically Useful Adrenoceptor Agonists and Antagonists

  • Agonists:

    • Adrenaline impacts blood pressure and heart rate

  • Antagonists: Used in hypertensive conditions

Page 11: Beta Adrenoceptor Agonists and Antagonists

  • Agonists: Salbutamol (asthma) and Dobutamine (cardiac failure)

  • Antagonists: Propranolol (anxiety), Atenolol (hypertension)

Page 12: Types of Neuromuscular Drugs

  • Differing effects of agonists vs. antagonists in autonomic control

  • Outcomes of ganglionic drugs affect overall autonomic function

Page 13: Somatic Motor Activity

  • ACh at NMJ is key to muscular function

  • Modifying skeletal muscle activity through nicotinic receptors affects contractions

Page 14: Nicotinic Drug Effects

  • Nicotinic Agonists: Induce temporary contraction, followed by relaxation

  • Nicotinic Antagonists: Cause sustained relaxation through channel inactivation

Page 16: Anticholinesterases in Treatment

  • Reversible: Increase ACh availability for treatment

  • Irreversible: Can lead to poisoning effects

Page 17: Effects of Sarin Poisoning

  • Symptoms include difficulty breathing and increased salivation due to excessive parasympathetic activity

Page 18: Pharmacological Effects in Anaesthetized Cats

  • Atropine increases BP/HR by removing parasympathetic influence

Page 19: Hexamethonium Effects

  • Profound hypotension due to reduced sympathetic activity; its removal shows prior autonomic tone

Page 20: Diaphragm Muscle Recording

  • Increased antagonist concentration reduces tension due to competition with ACh

Page 21: Neostigmine Effects

  • Increases ACh duration at NMJ, enhancing muscle tension

  • Useful in myastenia gravis for receptor restoration

Page 22: Neostigmine Functionality

  • Competes with tubocurarine at NMJ, reversing its blockage by prolonging ACh presence.