Medical Pharmacology Chapter 4:  Autonomic (ANS) Pharmacology: Introduction

 

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Autonomic Dysfunction continued
  • 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

 

Introduction and Part I

 

 

 

 

Expiration against a partially closed glottis

Rises due to aortic compression

Decreases

 

Part  II

Continued Expiration

Falls due to decreased venous return

Increases

sympathetic system

Part III

 

Continued Expiration

TPR increases (increased sympathetic discharge/plasma epinephrine)

Increases at a slower rate

Requires efferent sympathetic response

Part III

End of expiration

Falls due to increased capacitance of pulmonary bed

Increases further

 

Part 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 tilt and  tilt-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. If the spinothalamic tract is intact, 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)

    • Drugs may help to define specific abnormalities.  For example, Tyramine, an indirect sympathomimetic drug, 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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