Autonomic Pharmacology--Introduction-Lecture IV, 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
    • ß-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

 

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  • Autonomic Testing
    • Heart rate variation with deep breathing:
      • Parasympathetic test -- cardiovascular system
      • Results influenced by:
        1. patient's posture
        2. rate and depth of respiration (5-6 per minute; forced vital capacity (FVC) > 15 = normal)
        3. age
        4. medication
        5. hypercapnea
      • normal heart rate variation with deep breathing: (persons less than 20 years old -- lower limits of normal variation = 10-20 beats/minute; persons over 60 years old -- 5-8 beats per minute;)
        • -- respiratory sinus arrhythmia, i.e.heart rate variation with deep breathing is abolished by atropine
    • Valsalva Response:
      • What is tested?
        1. Afferent limb
        2. Central processing
        3. Efferent limb of the baroreceptor reflex
      • Protocol:
        1. constant expiratory pressure (40 mm Hg -- maintained for 15 seconds)
Phase Maneuver Blood Pressure Heart rate Notation

 I

 

Expiration against a partially closed glottis

Rises due to aortic compression

Decreases

  

 II (early) 

Continued Expiration

Falls due to decreased venous return

Increases

sympathetic system

 II (late) 

Continued Expiration

TPR increases (increased sympathetic discharge/plasma epinephrine)

Increases at a slower rate

Requires efferent sympathetic response

III

End of expiration

Falls due to increased capacitance of pulmonary bed

Increases further

  

IV

Recovery

Increases ("over shoot") due to the vasoconstricting state plus increased cardiac output

Compensatory bradycardia

sympathetic response -- BP overshoot; parasympathetic response-- bradycardia
adapted from Table 371-3 Engstrom, J, and Martin, J.B. Disorders of the Autonomic Nervous System, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 2374.

  • Orthostatic Blood Pressure Recordings:

    • Beat-to-beat heart rate variation dependent on:

      • supine/80 degree/tells-back positions

      • may detect vagal-mediated syncope

  • Cold Pressor Test:

    • Sympathetic function test:

      • one hand immersed in ice water

      • BP measured at 30 seconds and one-minute

      • normally: systolic/diastolic pressures rise by 10 to 20 mm Hg

        1. Afferent pathway: spinothalamic (distinct from afferent limb of baroreceptor reflex arc)

        2. Therefore abnormal responses are indicative of autonomic central processing or sympathetic outflow dysfunction

        3. When response to cold pressor test is normal and response to valsalva abnormal; lesion is located in the afferent limb of the baroreceptor reflex arc

  • Pharmacologic Tests

    • Very low supine plasma norepinephrine: indicative of postganglionic involvement (diabetes mellitus; pure autonomic failure)

    • Tyramine: -- indirect sympathomimetic increases blood pressure if neuronal norepinephrine stores are adequate and uptake mechanisms present;

    • Up-regulation of postsynaptic receptors (noradrenergic) -- suggestive of denervation lesions are reflected in an exaggerated response to norepinephrine infusion (but not to tyramine since tyramine effects depend on intact presynaptic stores)

    • CNS lesions show increased BP responsiveness to sympathomimetic agent

 

Engstrom, J, and Martin, J.B. Disorders of the Autonomic Nervous System, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 2372-2377.

 

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