Autonomic physiology and pharmacology

Purpose

• Regulates automatic bodily function

Function

• Sympathetic - 'flight or fight'
• Parasympathetic - 'rest and digest'

Functions often oppose each other

Some important functions include blood pressure control, thermoregulation and digestion

• CVS - blood pressure, cardiac output, vessel tone
• Respiratory - bronchial wall muscle tone
• GIT - secretion of saliva and digestive enzymes, movement of food through tract (peristalsis), relaxation of sphincters
• GUS - penile erection and ejaculation
• CNS - pupillary tone (pupil size), accomodation
• Skin - sweating, vasodilation

Anatomy

• Parasympathetic nuclei - brainstem or sacral segments of spinal cord ("cranial sacral outflow")
• Sympathetic nuclei - intermediate horn thoraco-lumbar spinal cord
• Parasympathetic ganglion - near organ of supply (exception are ciliary, pterygopalantine, submandibular, otic ganglion in head)
• Sympathetic ganglion - in sympathetic chain parallel to vertebral column (exceptions are superior, middle, inferior cervical ganglion in head; coeliac, superior mesenteric, inferior mesenteric ganglion of abdomen)

Pathways

Sympathetic

• Pre-ganglionic fibres have a short course as they exit the anterior root and enter the sympathetic chain via the white ramus communicans
• Post ganglionic neurons are unmyelinated when they leave the sympathetic chain via the gray ramus communicans and join the sensorimotor components of the spinal nerve and continuing on in the PNS.

Parasympathetic

• Pre-ganglion parasympathetic fibres are myelinated but they have a longer course until the reach the parasympathetic ganglion near the innervate organ.
• The short post-ganglionic fibres are unmyelinated.

Neurotransmitters

• Pre-ganglionic - Acetyl Choline (both)
• Post-ganglionic - Acetyl Choline (parasympathetic), Noradrenaline (sympathetic - except sweat glands which are cholinergic)

Receptor sub types and distribution

Cholinergic receptors and distribution

• Nicotinic (ganglionic) NG - pre-ganglionic
• Nicoctinic (muscle) NM - neuromuscular junction (not autononic - see motor system)
• Muscarinic - post-ganglionic (parasympathetic)

Adrenergic receptor

• Alpha-1 - vessels
• Alpha-2 - vessles
• Beta-1 - cardiac
• Beta-2 - vessels, bronchial muscle
• Beta-3 - pancreatic islet cells (insulin secretion)

Clinical effects

• Sympathetic activity consistent with the arousal state. Increased heart rate, blood pressure, ^ bronchodilatation (improve air flow), pupil dilatation (improve visual acuity), sweating (for thermoregulation during activity), vasoconstriction of gut, vasodilatation to muscle (divert blood flow to muscle)
• Parasympathetic activity consistent with the rest state. Slow heart rate, pupillary constriction, bronchoconstriction, pupillary constriction, increase GIT secretions and peristalsis

Autonomic pharmacology

Terminology

• Muscarinic antagonist = "anticholinergic"
• Muscarinic agonist = "cholinergic"
• Beta 1 adrenergic antagonist = "beta-blocker"
• Beta 2 adrenergic agonists = "beta 2 agonist"

Examples

• Inotropes (beta 1 adrenergic agonists) - stimulates heart resulting in increased heart pressure (treat shock)
• Vasopressors (alpha1 adrenergic agonists) - vasoconstriction resulting in increased blood pressure (treat shock)
• Beta blockers - lower blood pressure (treat hypertension)
• Positive chronotrope - (anticholinergic, beta 1 adrenergic agonists) - increase heart rate (treat heart block)
• Bronchodilators (beta 2 adrenergic agonist, anticholinergic) - brochodilatation (treat asthma)
• Various cholinergic agonists - improve urinary flow (treat urinary retention)
• Mydriatics / Cycloplegics (muscarinic antagonists) - pupil dilation (treat eye conditions, assist in examining eye)
• Miotics (beta adrenergic antagonists, muscarinic agonists) - pupil constriction (treat glaucoma)
• Antispasmodics (anticholinergic) - relax GIT/GUS smooth muscle (treat diarrhea, improve urinary flow or passage of stone)
• Anti-sialogue (anticholinergic) - reduces salivary and GIT secretions (pre-operative prep)
  due to widespread location of autonomic receptors side effects are common which both the clinician and patient should be aware of.
  many drugs also have indirect autonomic effects

Clinical toxicology - toxidromes

• Cholinergic e.g. nerve gas (Sarin), organophosphates - SLUDGE - salivation, lacrimation, urination, diarrhoea, gastric upset, emesis + bronchorrhea, bradycardia/hypotension [patients drown in their own secretions]
• Anticholinergic e.g. atropine, various psychotropic drugs - 'Mad as a hatter' - psychosis, 'Red as a beet' - skin vasodilatation,,, 'Dry as a bone' - loss of sweating, 'Hot as a hare' - inability to cool AND 'can't see, can't pee' - miosis, urinary retention + ^ HR
• Sympathomimetic e.g. amphetamines, cocaine - ^HR, ^BP, sweating (cf anticholinergic), agitation, hyperthermia, pupillary dilatation

NB anticholinergic similar to sympathomimetic toxidrome except one has dry skin and the other has wet.