Medical Physiology 2005

Autonomic Nervous System Problem Set

Section I. Cholinesterase inhibitors:

Background: The toxicological aspects of anti-cholinesterase inhibitors are of practical importance to the physician. In addition to numerous cases of accidental intoxication from the use and manufacture of cholinesterase inhibitors as agricultural insecticides, these agents are used frequently for homicidal and suicidal purposes. One class of cholinesterase inhibitor, the organophosphorus agents, account for as much as 80% of pesticide-related hospital admissions, and the World Health Organization documents pesticide toxicity as a widespread global problem.

Problems:

1. For a patient suffering from acute intoxication of a cholinesterase inhibitor, explain:

a. the rationale behind treating with atropine, and which tissues of the body are unaffected by this treatment..

b. what happens at the neuromuscular junction and the overall effect on skeletal muscle function.

2. Explain why therapeutic doses of a cholinesterase inhibitor would be used to treat myasthenia gravis, a neuromuscular disease characterized by weakness and marked fatigability of skeletal muscle and probably caused by an autoimmune response directed at the ACh receptor.

Section II: Sympathomimetic Agents:

Background: Activation of the sympathetic nervous system occurs in response to diverse stimuli in the normal healthy person including physical activity, psychological stress, changes in ambient temperature and a host of others. In addition, blood loss and many disease related provocations stimulate sympathetic output. According, due to the wide variety of effects, drugs the mimic (sympathomimetic) are used in a wide variety of clinical settings.

Problems:

1. The following drugs all have the ability to stimulate norepinephrine release from postganglionic sympathetic motor neurons, but by different mechanisms. Describe the mechanism of action of:

a. cocaine

b. caffeine

c. Ca²⁺ ionophores

2. The blood vessels that supply skeletal muscles contain a1 (and in some cases a2) and b2 adrenergic receptors. Explain why:

a. sympathetic stimulation or infusion with norepinephrine results in vasoconstriction.

b. infusion with isoproterenol results in vasodilation.

c. infusion with therapeutic doses of epinephrine will produce vasodilation, but increasing the dose of epinephrine will eventually result in vasoconsriction.

3. What is the advantage of treating patients suffering with asthma with a specific b2 agonist as opposed to isoproterenol or simply epinephrine?

Section III: Anti-cholinergic Agents:

1. The following drugs all have the ability to inhibit acetylcholine release from cholinergic nerve terminals, but by different mechanisms. Describe the mechanism of action of:

a. Hemicholinium

b. Vesamicol

c. Botulinus toxin

2. Two agents which block neuromuscular transmission are tubocararine and succinylcholine. Contrast the mechanisms of blockade for these two agents, and explain how prolonged exposure to succinylcholine can alter electrolyte balance in the body with potentially life threatening consequences.