Nursing Pharmacology Autonomic (ANS) Pharmacology: Introduction

• 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: from the Greek: at the side of 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

        • Plomotor 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.

     

    Parasympathetic System: Cranial-Sacral Outflow

     

    ANS Neurotransmitters: Effector Organs

    Eye

    Adrenergic

    Effects

    Cholinergic

    Iris: Radial Muscle	N.E., α1 receptor	contraction (mydriasis)	-----
    Iris: Sphincter muscle	-----	-----	contraction (miosis)
    Ciliary Muscle	N.E., β2 receptor	relaxation (far vision)	contraction (near vision)

     

    Heart

    Adrenergic

    Effects

    Cholinergic

    Sino-atrial (SA) Node	β1; β2	increase rate	decrease rate (vagal)
    Atrial muscle	β1, β2	increased: contractility, conduction velocity	decreased: contractility, action potential duration
    Atrio-ventricular (AV) node	β1, β2	increased: automaticity*, conduction velocity	decreased conduction velocity; AV block
    His-Purkinje System	β1, β2	increased: automaticity, conduction velocity	------
    Ventricles	β1, β2	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 cardiac fiber stretch

      •  β-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	α1,2; β2	constriction;dilatation	constriction
    Skin/Mucosa	α 1, 2	constriction	dilatation
    Skeletal Muscle	α; β2	constriction,dilatation	dilatation
    Cerebral	α1	slight constriction	dilatation
    Pulmonary	α1, β2	constriction; dilatation	dilatation
    Abdominal viscera	α1, β2	constriction; dilatation	-------
    Salivary glands	α1,2	constriction	dilatation
    Renal	α 1, 2; β1,2	constriction;dilatation	---------

     

    Systemic Veins

    Adrenergic Effects

    Cholinergic

    systemic veins

    α1,2; β2

    constriction; dilatation

    -----

     

    Lung

    Adrenergic Effects

    Cholinergic

    Tracheal and bronchial muscle	β2	Relaxation	contraction
    Bronchial glands	α1, β2	decrease secretion; increased secretion	stimulation

     

    Kidney

    Adrenergic Effects

    Cholinergic

    Renin Secretion

    α1; β1

    decrease; increase

    -------

     

    Skin

    Adrenergic Effects

    Cholinergic

    Pilomotor muscles	α1	contraction	-----
    Sweat glands	α1	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

    β2

    increased: contractility; glycogenolysis; potassium uptake

    ----------

     

    Liver

    Adrenergic Effects

    Cholinergic

    Liver

    α1;β 2

    glycogenolysis and gluconeogenesis

    --------

     

     

    Posterior Pituitary

    Adrenergic Effects

    Cholinergic

    Posterior Pituitary

    β 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 dominant.

      • 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.