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The Influence of Drugs on the ANS

Nervous

Drugs that affect the ANS can have important therapeutic value, and they can be used to treat certain diseases because they can increase or decrease activities normally controlled by the ANS. Drugs that affect the ANS can also be found in medically hazardous substances such as tobacco.

Direct-acting drugs bind to ANS receptors to produce their effects. For example, stimulating agents bind to specific receptors and activate them, and blocking agents bind to specific receptors and prevent them from being activated. The main topic of this essay is direct-acting drugs. It should be noted, however, that indirect-acting drugs can also influence the ANS. For example, some drugs indirectly produce a stimulatory effect by causing the release of neurotransmitters or by preventing the metabolic breakdown of neurotransmitters. Other drugs indirectly produce an inhibitory effect by preventing the biosynthesis or release of neurotransmitters.

Drugs that Bind to Nicotinic Receptors

Drugs that bind to nicotinic receptors and activate them are nicotinic (nik'-o-tin-ik) agents. Although these agents have little therapeutic value and are mainly of interest to researchers, nicotine is medically important because of its presence in tobacco. Nicotinic agents bind to the nicotinic receptors on all postganglionic neurons within the autonomic ganglia and produce stimulation. Responses to nicotine are variable and depend on the amount taken into the body. Because nicotine stimulates the postganglionic neurons of both the sympathetic and parasympathetic divisions, much of the variability of its effects results from the opposing actions of these divisions. For example, in response to the nicotine contained in a cigarette, the heart rate may either increase or decrease; and its rhythm tends to become less regular as a result of the simultaneous actions on the sympathetic division, which increase the heart rate, and the parasympathetic division, which decreases the heart rate. Blood pressure tends to increase because of the constriction of blood vessels, which are almost exclusively innervated by sympathetic neurons. In addition to its influence on the ANS, nicotine also affects the central nervous system; therefore not all of its effects can be explained on the basis of action on the ANS. Nicotine is extremely toxic, and small amounts can be lethal.

Drugs that bind to and block nicotinic receptors are called ganglionic blocking agents because they block the effect of acetylcholine on both parasympathetic and sympathetic postganglionic neurons. The effect of these substances on the sympathetic division, however, overshadows the effect on the parasympathetic division. For example, trimethaphan camsylate can be used to treat high blood pressure. It blocks sympathetic stimulation of blood vessels, causing the blood vessels to dilate, which decrease blood pressure. Ganglionic blocking agents have limited uses because they affect both sympathetic and parasympathetic ganglia. Whenever possible, more selective drugs are now used.

Drugs that Bind to Muscarinic Receptors

Drugs that bind to and activate muscarinic receptors are muscarinic (mus'ka-rin-ik) agents, or parasympathomimetic (par-a-sim'pa-tho-mi-met'ik) agents. These drugs activate the muscarinic receptors of target tissues for both divisions of the ANS. Most observable responses are parasympathetic because all the structures innervated by the parasympathetic division have muscarinic receptors, whereas almost all the structures innervated by the sympathetic division have adrenergic receptors. Muscarine causes increased sweating; increased secretion of glands in the digestive system; decreased heart rate; constriction of the pupils; and contraction of respiratory, digestive, and urinary system smooth muscles. Bethanechol chloride is a parasympathomimetic agent used to stimulate the urinary bladder following surgery, because the general anesthetics used for surgery can temporarily inhibit a person's ability to urinate. The drug helps to prevent the accumulation of urine until normal urinary bladder function returns.

Drugs such as atropine that bind to and block the action of muscarinic receptors are muscarinic blocking agents, or parasympathetic blocking agents. These drugs dilate the pupil of the eye and are used during eye examinations to allow the examiner to see the retina through the pupil. They also decrease salivary secretion and are used during surgery to prevent patients from choking on excess saliva while they are anesthetized.

Drugs that Bind to Alpha and Beta Receptors

Drugs that activate adrenergic receptors are adrenergic (a-dri-ner'jik) agents or sympathomimetic (sim'pa-tho-mi-met'ik) agents. Drugs such as phenylephrine stimulate alpha receptors, which are numerous in the smooth muscle cells of certain blood vessels, especially in the digestive tract and the skin. These drugs increase blood pressure by causing vasoconstriction. On the other hand, isoproterenol is a drug that selectively activates beta receptors, that are found in cardiac muscle and bronchiolar smooth muscle. Beta-adrenergic-stimulating agents are sometimes used to dilate bronchioles in respiratory disorders such as asthma and are occasionally used as cardiac stimulants.

Drugs such as phenoxybenzamine that bind to and block the action of alpha-receptors are alpha-adrenergic (a-dre-ner'jik) blocking agents. The therapeutic uses of these drugs are limited, but phenoxybenzamine is used for the treatment of pheochromocytoma (fe'o-kro-mo-si-to'mah). This disorder is usually caused by a noncancerous tumor of the adrenal medulla that results in the excessive release of norepinephrine. The norepinephrine stimulates vasoconstriction, causing high blood pressure. Phenoxybenzamine can help to lower blood pressure by blocking the effects of norepinephrine.

Propranolol (pro-pran'o-lol) is an example of a beta-adrenergic blocking agent. These drugs are sometimes used to treat high blood pressure, some types of cardiac arrhythmias, and patients recovering from heart attacks. Blockage of the beta receptors within the heart prevents sudden increases in the heart rate and thus decreases the probability of arrhythmic contractions.

Future Research

Our present knowledge of the ANS is more complicated than the broad outline presented here. In fact, there are subtype receptors for each of the major receptor types. For example, alpha receptors are subdivided into groups such as alpha-1A, alpha-1B, alpha-2A and alpha-2B receptors. The exact number of subtypes in humans in not yet known. However, their existence suggests the possibility of designing drugs that affect only one subtype. For example, a drug that affects the blood vessels of the heart but not other blood vessels might be developed. Such drugs could produce specific effects, yet would not produce undesirable side effects because they would act only on specific target tissues.

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