Autonomic nervous system

• The peripheral nervous system regulates functions with little or no voluntary control, via a pair of opposing systems - parasympathetic and sympathetic
• Which tissues are innervated by autonomic nerves?

  • smooth muscle
  • cardiac muscle
  • exocrine glands
  • endocrine glands
  • fat cells
• Autonomic nervous system uses separate neural pathways from somatic. Sympathetic and parasympathetic have very different origins and organisation.
• Parasympathetic spinal outflow: craniosacral
• Sympathetic spinal outflow: thoracolumbar
• Cranial nerves III, VII, IX and X have some autonomic function
• 2 parasympathetic neurone pathway

  • long preganglionic
  • short postganglionic

  ganglia are close to final destination
• Vagus nerve has multiple autonomic functions, including heart, lungs, GI tract, and motor and sensory function to larynx/pharynx (speech, airway protection)
• Sympathetic 2 neurone pathway

  • short preganglionic
  • long postganglionic

  Ganglia mostly in sympathetic chain
• Sympathetic nervous system directly innervates adrenal medulla from pre-ganglionic neurone to release adrenaline.
• Parasympathetic neurotransmitters

  • ganglion ACh (nicotinic)
  • terminal synapse ACh (muscarinic)
• M1 receptors are found in autonomic ganglia (synaptic transmission) and in the stomach (acid secretion).
• M2 receptors are found in the heart (bradycardia)
• M3 receptors are found in the bronchi (constriction), bladder (contraction), gut (increases peristalsis), eye (accommodation), salivary glands (secretion) and stomach parietal cells (acid secretion).
• M4 and M5 receptors are found in the CNS and have multiple roles.
• Acetylcholine is the neurotransmitter at all muscarinic receptor subtypes.
• Sympathetic neurotransmitters

  • ganglion ACh (nicotinic)
  • terminal synapse NA (ACh for sweating)
• alpha 1 receptors are found in arterioles (vasoconstriction) and bladder sphincter (constriction)
• alpha 2 receptors are found in presynaptic neurones (inhibition of release)
• beta 1 receptors are found in the heart (increase HR and increase contractility)
• beta 2 receptors are found in bronchi (bronchodilatation), muscle blood vessels (dilatation) and uterus (relaxation)
• beta 3 receptors are found in fat cells (lipolysis and thermogenesis)
• Noradrenaline is primarily the postganglionic sympathetic neurotransmitter
• Adrenaline is primarily released from the adrenal medulla.
• Drugs can

  • stimulate a receptor (agonist)
  • inhibit a receptor (antagonist)
• Drug actions in the nervous system can be

  • non-specific to a receptor type
  • non-selective beta-blocker propranolol
  • specific to a receptor subtype
  • selective beta 2 agonist salbutamol
• A 73 yo man has worsening difficulty passing urine. Investigations show this to be caused by benign prostatic hypertrophy. What classification of drug could help?

  alpha 1 antagonist
• Alpha 1 blockers (e.g. doxazosin) are used to treat urinary retention (side effect of hypotension). The short acting muscarinic agent bethanechol is a less-commonly used alternative.
• A 64 yo man has bradycardia of 35/min during a cystoscopy under local anaesthetic. What should be prescribed?

  Atropine (anti-muscarinic)
• The antimuscarinic drug atropine is normally the first line treatment for bradycardia. Alternatively isoprenaline or adrenaline can be used, acting via stimulation of beta 1 receptors.
• A 15 yo girl has a problem with excessive sweating in axillae. What type of receptor stimulates increased sweating?

  Cholinergic muscarinic receptors
• Sweating is mostly mediated by sympathetic cholinergic (muscarinic) fibres. Hyperhidrosis can be treated locally by Botox injections, which prevent synaptic ACh release
• A 57 yo woman has chronic open angle glaucoma. What is the mechanism of action of eye drops typically used to lower intraocular pressure?

  Muscarinic agonist
• Pilocarpine, a selective M3 agonist, is used to treat glaucoma, largely by constricting the pupil. Alpha 1 blockers can have a similar action on the pupil, though none is used in routine practice for glaucoma.
• 14 yo girl has anaphalactic reaction following IV antibiotic (she is very wheezy and profoundly hypotensive 62/25 mmHg). What are the main actions you would want from the ideal drug to treat her problem?

  alpha 1 agonist and b2 agonist
• Anaphylaxis results in profound histamine-induced hypotension and/or bronchospasm. Adrenaline (not noradrenaline) is the drug of choice by stimulating both alpha 1 and beta 2 receptors