Autonomic Pharmacology--Introduction-Lecture I, slide 2

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Table of Contents
  • ANS Anatomy
    • Autonomic and Somatic Innervation
    • Autonomic Reflex Arc
    • Autonomic Reflex Arc: First Link
    • Sensory Fiber Neurotransmitter(s)
    • Autonomic Nervous System Neurotransmitters: Summary
    • CNS and the Autonomic Nervous System
      • Spinal Cord Reflexes
      • Hypothalamus and Nucleus tractus solitarii
      • Higher Centers
    • Peripheral ANS Divisions
  • Comparison between Sympathetic & Parasympathetic Systems
  • Sympathetic Nervous System Anatomy
    • Diagram Sympathetic System
    • Anatomical Outline
      • Paravertebral Ganglia
      • Prevertebral Ganglia
      • Terminal Ganglia
      • Adrenal Medulla
  • Parasympathetic System Anatomy
  • ANS Neurotransmitter Effector Organs
  • Eye
  • Heart
  • Arterioles
  • Systemic Veins
  • Lung

 

  • Skin
  • Adrenal Medulla
  • Skeletal Muscle
  • Liver
  • Posterior Pituitary

 

  • Interactions between Sympathetic & Parasympathetic Systems
  • "Fight or Flight": Characteristics of the ANS
  • ANS Neurotransmission
    • Neurotransmitter Criteria
    • Neurotransmission Steps:
      • Axonal Conduction
      • Storage and Release of Neurotransmitter
      • Combination of Neurotransmitter and Post-Junctional Receptors
      • Termination of Neurotransmitter Action
      • Other Non-electrogenic Functions
    • Cholinergic Neurotransmission
      • Transmitter Synthesis and Degradation
      • Acetylcholinesterase
      • Acetylcholine: Storage and Release
      • Site Differences:
        • Skeletal Muscle
        • Autonomic Effectors
        • Autonomic Ganglia
        • Blood vessels
      • Signal Transduction: Receptors
  • Adrenergic Transmitters: Biosynthetic Pathways
  • Adrenergic Neurotransmission: Introduction to the Neurotransmitters
  • Catecholamine Synthesis, Storage, Release and Reuptake
    • Enzymes
    • Catecholamine storage
    • Regulation of adrenal medullary catecholamine levels
    • Reuptake
    • Metabolic Transformation
    • Indirect-acting sympathomimetics
    • Release
  • Adrenergic Receptor Subtypes
    • -adrenergic receptors
    • Alpha-adrenergic receptors
    • Catecholamine Refractoriness
  • Other Autonomic Neurotransmitters
    • Co-transmission
      • ATP
      • VIP
      • Neuropeptide Y family
    • Purines
    • Nitric Oxide (Modulator)
  • Predominant Sympathetic/Parasympathetic Tone
  • Baroreceptor Reflexes
  • Pharmacological Modification of Autonomic Function
  • Autonomic Dysfunction

 

Sympathetic Nervous System

Anatomical Outline
  • Cell bodies of preganglionic fibers: found in intermediolateral columns of the spinal cord (first thoracic to second or third lumbar segments
  • Preganglionic fiber axons synapse with sympathetic ganglionic neurons which lie outside the cerebrospinal axis.
  • Sympathetic ganglia are found at three sites:
    • Paravertebral
    • Prevertebral
    • Terminal
  •  Paraverebral ganglia: 22 interconnected pairs on either sides of the vertebral column. (para: Gr: at the side or along side)
    • Myelinated preganglionic fibers (white rami: thoracolumbar outflow only) leave through the anterior spinal roots.
    • Postganglionic fibers (gray rami) runs back to spinal nerves for distribution to:
      • blood vessesls of the skin
      • blood vessels of skeletal muscle
      • sweat glands
      • pilomotor muscles
  •   Prevertebral Ganglia: abdominal and pelvic location, comprised of:
    • celiac ganglia
    • superior mesenteric ganglia
    • aorticorenal and inferior mesenteric ganglia

 

  •   Terminal Ganglia: few, residing near the innervated organ, including
    • ganglia associated with the urinary bladder and rectum
    • cervical ganglia (neck): three ganglia (chain) mediating vasomotor, secretory, pupillodilatory and pilomotor responses of the head and neck)
    • All postganglionic fibers arise from cell bodies located within these ganglia; the preganglionic fibers come from upper thoracic segments: No sympathetic preganglionic fibers come from above the first thoracic level

 

  • Adrenal medulla is similar to sympathetic ganglia.
    • Difference:
      • Epinephrine is released (post-ganglionic sympathetic fibers release norepinephrine)
    • Chromaffin cells are innerved by preganglionic fibers that release acetylcholine.

Lefkowitz, R.J, Hoffman, B.B and Taylor, P. Neurotrasmission: The Autonomic and Somatic Motor Nervous Systems, In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, pp.105-107.

 

 

ANS Neurotransmitters: Effector Organs

Eye
   

Adrenergic

Effects

  Cholinergic
Iris: Radial Muscle N.E., alpha-1 receptor contraction (mydriasis)

-----

Iris: Sphincter muscle

-----

-----

contraction (miosis)
Ciliary Muscle N.E., beta2 receptor relaxation (far vision) contraction (near vision)

 

Heart
   

Adrenergic

Effects

  Cholinergic
Sino-atrial (SA) Node beta1; beta2 increase rate decrease rate (vagal)
Atrial muscle beta1, beta2 increased: contractility, conduction velocity decreased: contractility, action potential duration
Atrio-ventricular (AV) node beta1, beta2 increased: automaticity*, conduction velocity decreased conduction velocity; AV block
His-Purkinje System beta1, beta2 increased: automaticity, conduction velocity

------

Ventricles beta1, beta2 increased: contractility, conduction velocity, automaticity, ectopic pacemaker small decrease in contractility
  • *An increase in the slope of phase 4 depolarization results in ENHANCED AUTOMATICITY.

  • As a result of the increase in phase 4 slope the cell reaches threshold more often, with a higher heart rate as a result.

Factors that increase phase 4 depolarization include
 mechanical stretch  beta-adrenergic stimulation  hypokalemia
  •  Ischemia can induce abnormal automaticity, i.e. automaticity that occurs in cells not typically exhibiting pacemaker activity.
    • Acetylcholine is an example of an agent that decreases the slope of phase 4 depolarization and as a result, slows the heart rate.

 

Arterioles

 

Adrenergic

Effects

Cholinergic
Coronary alpha 1, 2; beta2 constriction;dilatation constriction
Skin/Mucosa alpha 1, 2 constriction dilatation
Skeletal Muscle alpha; beta2 constriction,dilatation dilatation
Cerebral alpha1  slight constriction dilatation
Pulmonary alpha1, beta2 constriction; dilatation dilatation
Abdominal viscera alpha1, beta2 constriction; dilatation -------
Salivary glands alpha1,2 constriction dilatation
Renal alpha 1, 2;beta1,2 constriction;dilatation ---------

Systemic Veins

 

Adrenergic Effects

Cholinergic
systemic veins alpha1,2; beta2 constriction; dilatation

-----

 

Lung

   

Adrenergic Effects

Cholinergic
Tracheal and bronchial muscle beta2 Relaxation contraction
Bronchial glands alpha1, beta2 decrease secretion; increased secretion stimulation

 

Kidney
 

Adrenergic Effects

Cholinergic
Renin Secretion alpha1; beta1 decrease; increase -------

 

Skin

   

Adrenergic Effects

Cholinergic
Pilomotor muscles alpha1 contraction -----
Sweat glands alpha1 localized secretion generalized secretion

 

Adrenal Medulla

 
 

Adrenergic Effects

Cholinergic
Adrenal medulla -- ---- Secretion of epinephrine and norepinephrine (mainly nicotinic and some muscarinic)

Skeletal Muscle

 
   

Adrenergic Effects

Cholinergic

Skeletal Muscle

beta2 increased: contractility;
glycogenolysis; potassium uptake
----------

 

Liver
   

Adrenergic Effects

Cholinergic
Liver alpha1;beta 2 glycogenolysis and gluconeogenesis --------

 

Posterior Pituitary

   

Adrenergic Effects

Cholinergic
Posterior Pituitary beta 1 Antidiuretic hormone secretion (ADH) ------------

 

 

Based on Table 6-1: Lefkowitz, R.J, Hoffman, B.B and Taylor, P. Neurotransmission: The Autonomic and Somatic Motor Nervous Systems, In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, pp.110-111

Characteristics of Autonomic Organ Innervation
  • Usually, parasympathetic and sympathetic systems are physiological antagonists; that is, if one system facilitates or augments a process the other system inhibits the process.

  • Since most visceral organs are innervated by both system, the activity of the organ is influenced by both, even though one system may be dominent.

  • The general pattern of antagonism between sympathetic and parasympathetic systems is not always applicable. The interaction between sympathetic and parasympathetic systems may be independent or interdependent.

Examples of Antagonistic Interactions between Sympathetic and Parasympathetic Systems
  • Actions of sympathetic and parasympathetic influences on the heart.

  • Actions of sympathetic and parasympathetic influences on the iris.

 

Interdependent or Complementary Sympathetic and Parasympathetic Effects
  • Actions of sympathetic and parasympathetic systems on male sexual organs are complementary.

 

Independent Effects
  • Vascular resistance is mainly controlled by sympathetic tone.

 

 

Fight or Flight: General Functions of the Autonomic Nervous System
ANS regulates organs/processes not under conscious control including:

circulation

digestion

respiration

temperature

sweating

metabolism

some endocrine gland secretions

  • Sympathetic system is most active when the body needs to react to changes in the internal or external environment: The requirement for sympathetic activity is most critical for:

temperature regulation regulation of glucose levels rapid vascular response to hemorrhage

reacting to oxygen deficiency

  • During rage or fright the sympathetic system can discharge as a unit--affecting multiorgan systems.

    • Sympathetic fibers show greater ramification.
    • Sympathetic preganglionic fibers may traverse through many ganglia before terminiating at its post-ganglionic cell. Synaptic terminal arborization results in a single preganglionic fiber terminating on many post-ganglionic cells.
    • This anatomical characteristic is the basis for the diffuse nature of sympathic response in the human and other species.
  • Fight or Flight sympathetic reaction affects many systems:

 Sympathetic Responses
heart rate increases

blood pressure increases

blood is shunted to skeletal muscles

blood glucose increase

bronchioles dilate

pupils dilate

many of these effects are primarily due to or augmented by epinephrine release from the adrenal medulla
  • Parasympathetic system controls more discretely, reducing the level of resting organ function.

Parasympathetic responses
slows heart rate lowers blood pressure increases gastrointestinal motility
protects retina from excessive light empties the bowel and bladder promotes absorption of nutrients

Lefkowitz, R.J, Hoffman, B.B and Taylor, P. Neurotrasmission: The Autonomic and Somatic Motor Nervous Systems, In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, pp.108..

 

 

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