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Autonomic Nervous System (ANS) and Somatic Nervous System (SNS)

• The ANS is the part of the PNS and visceral nervous system that is a control system, functions below consciousness, and directly controls visceral functions.

• The SNS functions by managing voluntary muscles, ie skeletal muscles.

• The ANS affects several functions including the heart rate, digestion rate, respiration rate, salivation, perspiration, the diameter of pupils, micturition (urination), and sexual arousal

• Inhibitory and excitatory synapses exist between neurones within these systems

• The sympathetic and parasympathetic divisions function in opposition to each other

  • The opposition operates in a complimentary and antagonistic manor
  • The sympathetic division can be considered the accelerator
  • The parasympathetic division can be considered the brake

• The sympathetic division typically functions in quick responses requiring quick reactions

• The parasympathetic division functions for actions not requiring immediate reactions

  • The sympathetic division can be considered "fight or flight"
  • The parasympathetic division can be considered "rest and digest"

Sympathetic Nervous System

• Promotes a "fight or flight" response corresponding with arousal and energy generation while inhibiting digestion.
• Diverts flood flow away from the gastro-intestinal (GI) tract and skin through vasoconstriction.
• Maintains and enhances blood flow to skeletal muscles and the lungs, up to 1200% increase in skeletal muscles.
• Dilates bronchioles which allows greater alveolar oxygen exchange.
• The heart rate and contractility of cardiac cells (myocytes) increases to enhance blood flow to skeletal muscles.
• Dilates pupils and relaxes the lens, allowing more light to enter the eye.
• Vasodilation occurs in the coronary vessels of the heart.
• Constricts all the intestinal sphincters and the urinary sphincter, and inhibits peristalsis

Parasympathetic Nervous System

• Promotes a "rest and digest" response, calming the nerves, return to normal function, and enhancing digestion.
• Dilates blood vessels leading to the GI tract, increasing blood flow.
• Important following food consumption because of metabolic demands.
• The bronchiolar diameter is constricted when the need for oxygen is diminished
• Dedicated cardiac branches of the Vagus and thoracic Spinal Accessory nerves impart Parasympathetic control of the Heart or Myocardium.
• Constriction of the pupil and lens occur during accommodation.
• Salivary gland secretion is stimulated, and peristalsis is accelerated.
• Appropriate parasympathetic nervous system (PNS) activity mediates food digestion and, indirectly, nutrient absorption.
• Is also responsible with erection of genitals through the pelvic splanchnic nerves.

Cholinergic Receptors

• Two families of cholinergic receptors exist: Muscarinic and Nicotinic
• Muscarinic receptors:
  • Belong to the class of G protein-coupled receptors (metabotropic receptors)
  • Recognise muscarine, an Alkaloid from mushrooms
  • Include the subtypes M1, M2, M3, M4 & M5
  • Found on ganglia of the peripheral nervous system, autonomic effector organs, the heart, smooth muscle, brain, and exocrine glands.
  • M1 receptors are also found on gastric parietal cells
  • M2 receptors are found on cardiac cells and smooth muscle
  • M3 receptors are found on the bladder, exocrine glands, and smooth muscle.
• Nicotinic receptors:
  • Recognise nicotine but only show a weak affinity for muscarine
  • Composed of 5 subunits functioning as a ligand-gated ion channel
  • Located in the CNS, adrenal medulla, autonomic ganglia, and neuromuscular junction (NMJ) in skeletal muscles.

Adrenergic Receptors

• Two main receptor families: α receptors and β receptors
• Receptors primarily bind Norepinephrine (NE) and epinephrine (EN)
• Subtypes include α 1, α 2, β1 & β2
• Adrenergically-innervated organs and tissues usually have a predominant receptor type
• The vasculature of skeletal muscle has both α1 ​​and β2 receptors, beta 2 ​​receptors are predominant
• The heart contains predominantly beta 1 ​receptors

Effects Mediated by α- and β-Adrenoceptors

• Alpha 1:

  • Vasoconstriction
  • Increased peripheral resistance
  • Increased blood pressure
  • Mydriasis
  • Increased closure of the internal sphincter of the bladder

• Alpha 2:

  • Inhibition of norepinephrine release
  • Inhibition of acetylcholine release
  • Inhibition of insulin release

• Beta 1:

  • Tachycardia
  • Increased lipolysis
  • Increased myocardial contractility
  • Increased renin release

• Beta 2:

  • Vasodilation
  • Decreased peripheral resistance
  • Bronchodilation
  • Increased muscle and liver glycogenolysis
  • Increased release of glucagon
  • Relaxed uterine smooth muscle

Neurotransmitters and Pharmacology

• Acetylcholine is the preganglionic neurotransmitter for both divisions and the transmitter for parasympathetic neurons.
• Nerves that release acetylcholine are cholinergic.
• Ganglionic neurons use acetylcholine to stimulate muscarinic receptors in the parasympathetic system.
• Sympathetic ganglionic neurons release noradrenaline (norepinephrine) to act on adrenergic receptors to effector organs.
• Acetylcholine acts on nicotinic receptors in the presynaptic neuron of the adrenal cortex because there is no postsynaptic cortex; the stimulation of the adrenal medulla releases adrenaline (epinephrine) into the bloodstream, acting on adrenoceptors.

Receptors and Organs - Functions

The Eye

• The ciliary epithelium produces aqueous humor through β₁ receptors, which maintains pressure to focus light on the lenses and retinae.
• Alpha receptors in the iris contract longitudinally when stimulated by sympathetic activity. The ciliary muscle and sphincter are stimulated by parasympathetic neurons releasing acetylcholine (Ach), and in turn bind muscarinic receptors. These muscles work by:
• pulling the iris towards itself, concentrically opening the sphincter
• ciliary muscle pulls on the trabecular meshwork to open the canal of schlemm and drain the fluid
  • ciliary muscle contracts the entire machinery to accommodate the lens by relaxing its pull on the lens
  • the sphincter contracts to constrict the pupil
• Under high stress, sympathetics release epinephrine and nonepinephrine (α,β), which increases aqueous humor production and dilates the pupil
• Under no stress, Parasympathetics constrict the pupil and drain the anterior chamber
• Ciliary epithelium produces aqueous humor through beta 1 receptors

The Lungs

• During sympathetic activity, beta 2 receptor stimulation creates bronchodilation of the airways while decreasing airway secretions.
• During parasympathetic activity, acetylcholine stimulates M receptors to bronchoconstrict the airways while increasing secretions.

The Heart

• During sympathetic activity, beta 1 recptor stimulation increases the heart rate, contractility, AV nodal conduction, and cardiac output.
• During parasympathetic activity, muscarinic receptor stimulation decreases SA nodal firing, AV node conduction, and CO.

The Blood Vessels

• The blood vessels express alpha, beta, dopamine, histamine, and muscarininc receptors
• During sympathetic activity, NE (alpha, beta 1), epinephine (alpha 1, alpha 2, beta 1, beta 2), and dopamine are relesed:
  • a1 vasoconstricts vessels, mainly arterioles, to increase pressure or restrict blood flow to organs and shunt it to others
  • beta 2 vasodilates skeletal vessel beds to increase blood flow to needed muscles
  • beta 2 lowers vasscular resitance, thus lowering overall pressure

Gastrointestinal Tract (GIT)

• Parasympathetic activity stimulates the muscarinic receptor (M), increasing GI motility, allowing sphincters to open, and secretion production.
• Sympathetic activity stimulates α and β receptors, slowing GI motility, increasing sphincter tone, and decreasing GI secretion.
• DA receptor activation causes increased GI motility, stimulates secretion, and decreases sphincter tone.
• Opioids must be considered when referring to GI functions; they decrease motility, secretions, and increase sphincter tone, inducing constipation.
• In kidneys, Alpha receptors and also prevent blooder contractions

Drugs Affecting the ANS

The Eye

• Glaucoma occurs due to increased intraocular pressure from increased production and decreased drainage of aqueous humor, and leads blindness.
• The eye is treated through cholinomimetics, β-blockers and epinephrine
  • Cholinomimetics tertiary amines easily pass through membranes, including pilocarpine and physostigmine Pilocarpine stimulates M receptors on the ciliary muscle and the sphincter muscle of the iris, which-
  • helps open the canal of schlemm
  • is a direct muscarinic agonist that passes through the cornea physostigmine is a cholinesterase inhibitor also passes through the cornea, the blood brain barrier, and increases concentration of local acetylcholine to contstrict both ciliary muscle and sphincter muscle
  • While both have same effect, pilocarpine does not pass into the blood brain barrier easily
  • Since Pilocarpine's charge is more specific, there are less central nervous system effects.
• The beta blocker of choice for glaucoma is Timolol
  • which blocks beta 1 and 2 receptors, and increases aqueous humor
  • crosses the cornea more effectively than other blockers, but lacks the anesthetic effect
• Acetazolamide is a diuretic drug where no HCO3 which limits the capacity to create aqueous humor

The Lungs

• Drugs that influence the action of the lungs affect airway diameter and airway secretions.
  • Control of the two receptors are regulated by beta 2 and also M receptors
• Epinephrine and and dopamine are sympathetic, and are also Bronchodilators
• Stimulate Beta 2 with -epinephrine or exogenous B2 agonists (albuterol, salbutamol)
• The antimuscarinic agent, ipratropium, a muscarinic receptor antagonist, is very effective in blocking muscarinic bronchoconstriction and increased secretion
• Epinephrine and Dopamine only for emergencies where increased ventilation as required as a drug

The Heart

• Heart activity is controlled through β₁ and M receptors.
• Beta 1 stimulation increases heart rate, contractility and cardiac output
• While in contrast Epinephrine, Norepinephrine, dopamine and isoproterenol all increase heart activity.
• Muscarinic receptor agonists or cholinesterase antagonists increase Ach, slowing the heart rate, decreasing contractility and decreasing AV nodal conduction velocity through the AV node
• Atenolol and metoprolol are both Beta ​​1 specific, and therefore the best Beta ​​blocker for use in asthmatics otherwise, nonselective beta blockers exacerbate a beta exacerbation

Blood Vessels

• To increase blood flow or blood vessels
• Blood pressure must be considered