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Much of the action of the body in maintaining cardiovascular, gastrointestinal, and thermal homeostasis occurs through the autonomic nervous system (ANS). The ANS is also our primary defense against challenges to that homeostasis. It provides involuntary (i.e., outside of consciousness) control and organization of maintenance and stress responses. In the words of Claude Bernard, "... nature thought it provident to remove these important phenomena from the capriciousness of an ignorant will." Activation of the sympathetic nervous system elicits what is traditionally called the fight or flight response, including redistribution of blood flow from the viscera to skeletal muscle, increased cardiac function, sweating, salivation, and pupillary dilation. The parasympathetic system governs activities of the body more closely associated with maintenance of function, such as digestive and genitourinary functions. A major goal of anesthetic administration is maintaining optimum homeostasis in the patient despite powerful challenges to a sometimes tenuous physiologic balance. The intelligent administration of anesthetic care to patients requires knowledge of ANS pharmacology to achieve desirable interactions of anesthetics with the involuntary control system and to avoid responses or interactions with deleterious effects. Disease states may impair ANS function to a significant extent and may thereby alter the expected responses to surgery and anesthesia. Possible negative effects of the human stress response have long been appreciated, and considerable effort has been expended in examining the possibility that modification or ablation of the stress response may improve perioperative outcome.
Initially, nerves were thought to be connected in a giant syncytium. Claude Bernard, a student of Magendie, postulated the theory of chemical synapse transmission. Later, Sherrington initiated a systemic study of reflexes and described some characteristics of reflex function. A chemist, J.J. Abel, first synthesized epinephrine in 1899, and his student Langley demonstrated that it caused the same effect as stimulating postganglionic sympathetic neurons. When the nerve was cut and epinephrine was injected, Langley found that there was a more profound effect, demonstrating denervation supersensitivity. From these observations, the concept of chemical transmission in the ANS developed. Sir Henry Dale isolated choline and studied an ester, acetylcholine, in animals. He demonstrated
Nerves are traditionally classified by the chemical transmitters they contain. Nerves containing acetylcholine are called cholinergic, whereas those containing norepinephrine or epinephrine are called adrenergic. In addition to classifying nerves, the term cholinergic refers to other structures or functions that relate in some way to acetylcholine. For instance, cholinergic receptors (i.e., cholinoceptors) are proteins in cell membranes that react with acetylcholine and cause the cell to respond in a characteristic way (e.g., muscles contract, glands secrete). Cholinergic agonists are drugs that act like acetylcholine on cholinoceptors to cause the cell to react in its characteristics way. They are sometimes referred to as cholinomimetic drugs. Cholinergic antagonists are drugs that react with cholinoceptors to block the access by acetylcholine and thereby prevent its action. These drugs may also be referred to as cholinolytic, cholinergic-blocking, or anticholinergic drugs.
Because muscarine, a chemical isolated from a mushroom, causes effects similar to those produced by activation of the parasympathetic nervous system, it was thought to be the endogenous parasympathetic transmitter. Since then, drugs that mimic the effects of muscarine on the parasympathetically innervated structures, including the heart, smooth muscles, and glands, have been called muscarinic drugs.
In the early 1900s, nicotine was found to act on ganglionic and skeletal muscle synapses and on nerve membranes and sensory endings. Accordingly, drugs that act on these parts of the cholinergic system are called nicotinic drugs. Nicotinic drugs that are more specific in their action have been discovered and are referred to by the name of the system they affect, such as ganglionic drugs or neuromuscular drugs. Agonists and antagonists exist in each category, with little crossover of effect between drugs acting at the ganglia and those acting at the neuromuscular junction.
Figure 16-1
Autonomic nervous system neurotransmission. ACh, acetylcholine;
Epi, epinephrine; NE, norepinephrine.
For purposes of this chapter, cholinergic nerves include the following ( Fig. 16-1 ):
Drugs mimicking the action of norepinephrine are referred to as sympathomimetic, whereas drugs inhibiting these effects of norepinephrine are called sympatholytic. Norepinephrine is the transmitter acting at adrenergic nerves, whereas epinephrine and norepinephrine are released by the adrenal medulla.
Adrenergic receptors have been identified and subdivided into α- and β-receptors and further subdivided into α1 , α2 , β1 , β2 , and other types. α2 -Adrenergic receptors are primarily located on the presynaptic membrane, whereas α1 -adrenergic receptors mediate smooth muscle vasoconstriction. The β1 -adrenergic receptors are found primarily on cardiac tissue, and β2 -adrenergic receptors mediate smooth muscle relaxation in some organs. We define adrenergic neurons as follows:
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