Autonomic Pharmacology Notes

Introduction to Autonomic Pharmacology

• The autonomic nervous system (ANS) plays a crucial role in regulating involuntary bodily functions.
• Dr. Graeme Sills presented an introduction to autonomic pharmacology on October 7, 2024.
• The course schedule includes lectures on receptor distribution, pharmacology of the autonomic nervous system, and practical lab sessions.

Basic Structure & Function of Neurons

• Key components of a neuron include:
  • Nucleus: Contains the cell's genetic material.
  • Axon Hillock: Initiates action potentials.
  • Dendrites: Receive signals from other neurons.
  • Neurons form complex networks to transmit signals throughout the body.

Organisation of the Nervous System

• Central Nervous System (CNS): Comprises the brain and spinal cord.

  • Efferent Signals: Transmit commands away from the CNS.

• Peripheral Nervous System (PNS): Divided into:

  • Somatic Nervous System: Controls voluntary movements (e.g., skeletal muscle).
  • Autonomic Nervous System (ANS): Regulates involuntary processes (e.g., heart rate, digestion).
  • Includes sympathetic, parasympathetic, and enteric divisions.

Divisions of the Nervous System

• Sympathetic Division: Involved in the body’s 'fight or flight' response; increases energy and alertness.
• Parasympathetic Division: Responsible for 'rest and digest' functions; conserves energy and promotes maintenance activities.
• Enteric Nervous System (ENS): Manages gastrointestinal functions independently of the CNS.

Function of the ANS

• The ANS regulates vital functions that are predominantly involuntary, including:
  • Heart rate and force of contraction.
  • Smooth muscle contraction/relaxation in vascular and visceral tissues.
  • Secretions from exocrine and endocrine glands.
  • Metabolic activities, particularly in the liver and skeletal muscle.
  • Immune modulation.
• Some ANS functions can become conscious with training (e.g., bladder control).

Sub-divisions of the ANS

• Efferent responses in the ANS feature:
  • Two neurons in series: Preganglionic and postganglionic neurons.
  • Sympathetic: Short pre-ganglionic fibers, long post-ganglionic fibers.
  • Parasympathetic: Long pre-ganglionic fibers, short post-ganglionic fibers; found close to or within target tissues.

Chemical Transmission in the Sympathetic Division

• Action potentials initiate neurotransmitter release:
  • ACh (acetylcholine) acts on nicotinic receptors at the pre-ganglionic level.
  • Noradrenaline (NA) is released at the post-ganglionic level, acting on adrenoceptors in target tissues.
  • Mechanism involves calcium entry leading to neurotransmitter release through exocytosis.

Key Receptors in the Sympathetic Division

• Nicotinic Receptors: Ligand-gated ion channels located on post-ganglionic neuron bodies.
• Adrenoceptors: G-protein coupled receptors acting on effector cells; further divided into alpha (α) and beta (β) subtypes:
  • Alpha Receptors: α1, α2 (various subtypes).
  • Beta Receptors: β1, β2, β3 (to mediate various responses).

Chemical Transmission in the Parasympathetic Division

• Similar mechanism to sympathetic for action potential transmission:
  • ACh acts on nicotinic receptors initially and subsequently on muscarinic receptors at the effector level.

Key Receptors in the Parasympathetic Division

• Muscarinic Receptors: G-protein coupled receptors (GPCRs) responding to ACh;
  • Subtypes: M1 (neural), M2 (cardiac), M3 (glands & smooth muscle), M4 & M5 (CNS).

Other ANS Transmitters

• NANC Transmitters: Non-adrenergic, non-cholinergic neurotransmitters enhancing or modulating autonomic functions.
  • Examples include Nitric Oxide (NO) and VIP (vasoactive intestinal polypeptide) in parasympathetic pathways.
  • ATP and neuropeptide Y from sympathetic neurons.

Activities of the ANS

• Sympathetic Stimulation: Effects include increased heart rate, bronchodilation, and reduced gut motility.
• Parasympathetic Stimulation: Effects include decreased heart rate, bronchoconstriction, and increased gastrointestinal activity.

Drug Effects on the ANS

• Various drugs target the ANS:
  • Beta Agonists: Increase heart rate and coronary blood flow (e.g., dobutamine).
  • Beta-blockers: Typical for reducing heart rate and blood pressure (e.g., atenolol).
  • Muscarinic Antagonists: Utilized for treating spasms and pupil dilation (e.g., atropine).

Summary

• The autonomic nervous system is integral for physiological homeostasis, managing involuntary functions through a complex interplay of sympathetic and parasympathetic divisions.
• Understanding its pharmacology is essential for effective drug therapy targeting various systems in the body.