Nervous system

There are two major control systems in the body: the nervous system and the endocrine system. Both systems of control can be manipulated by drug therapy, which either mimics or blocks the usual action of the control system, to produce or inhibit physiologic effects. The endocrine system is considered separately in Chapter 11, which discusses the corticosteroid class of drugs. The nervous system is divided into the central nervous system (CNS) and the peripheral nervous system (PNS), both of which offer sites for drug action. The overall organization of the nervous system may be outlined as follows:

Figure 5-1 is a functional, but not anatomically accurate, diagram of the central and peripheral nervous systems. The sensory branch of the nervous system consists of afferent neurons from heat, light, pressure, and pain receptors in the periphery to the CNS. The somatic portion (or motor branch) of the nervous system is under voluntary, conscious control and innervates skeletal muscle for motor actions such as lifting, walking, or breathing. This portion of the nervous system is manipulated by neuromuscular blocking agents, to induce paralysis in surgical procedures or during mechanical ventilation. The autonomic nervous system is the involuntary, unconscious control mechanism of the body, sometimes said to control vegetative or visceral functions. For example, the autonomic nervous system regulates heart rate, pupillary dilation and contraction, glandular secretion such as salivation, and smooth muscle in blood vessels and the airway. The autonomic nervous system is divided into parasympathetic and sympathetic branches.

Autonomic branches

Neither motor nor sensory branch neurons have synapses outside of the spinal cord before reaching the muscle or sensory receptor site. The motor neuron extends without interruption from the CNS to the skeletal muscle, and its action is mediated by a neurotransmitter, acetylcholine (Ach). This is in contrast to the synapses occurring in the sympathetic and parasympathetic divisions of the autonomic system. The multiple synapses of the autonomic system offer potential sites for drug action, in addition to the terminal neuroeffector sites.

The parasympathetic branch arises from the craniosacral portions of the spinal cord and consists of two types of neurons—a preganglionic fiber leading from the vertebrae to the ganglionic synapse outside the cord and a postganglionic fiber from the ganglionic synapse to the gland or smooth muscle being innervated. The parasympathetic branch has good specificity, with the postganglionic fiber arising very near the effector site (e.g., a gland or smooth muscle). As a result, stimulation of a parasympathetic preganglionic neuron causes activity limited to individual effector sites, such as the heart or the eye. Figure 5-2 illustrates the portions of the spinal cord where the parasympathetic and sympathetic nerve fibers originate.

The sympathetic branch arises from the thoracolumbar portion of the spinal cord and consists of short preganglionic fibers and long postganglionic fibers. Sympathetic neurons from the spinal cord terminate in ganglia that lie on either side of the vertebral column. In the ganglia, or the ganglionic chain, the preganglionic fiber makes contact with postganglionic neurons. As a result, when one sympathetic preganglionic neuron is stimulated, the action passes to many or all of the postganglionic fibers. The effect of sympathetic activation is widened further because sympathetic fibers innervate the adrenal medulla and cause the release of epinephrine into the general circulation. Circulating epinephrine stimulates all receptors responding to norepinephrine, even if no sympathetic nerves are present. Where the parasympathetic system allows discrete control, the design of the sympathetic system causes a widespread reaction in the body.

In the parasympathetic branch, the neurotransmitter Ach conducts nerve transmission at the ganglionic site and at the parasympathetic effector site at the end of the postganglionic fiber. This action is illustrated in Figure 5-3. The term neurohormone has also been used in place of neurotransmitter. Ach is concentrated in the presynaptic neuron (both at the ganglion and at the effector site). Ach is synthesized from acetyl-CoA and choline, catalyzed by the enzyme choline acetyltransferase. Ach is stored in vesicles as quanta of 1000 to 50,000 molecules per vesicle. When a nerve impulse (action potential) reaches the presynaptic neuron site, an influx of calcium is triggered into the neuron. Increased calcium in the neuron causes cellular secretion of the Ach-containing vesicles from the end of the nerve fiber. After release, the Ach attaches to receptors on the postsynaptic membrane and initiates an effect in the tissue or organ site.

Ach is inactivated through hydrolysis by cholinesterase enzymes, which split the Ach molecule into choline and acetate, terminating stimulation of the postsynaptic membrane. In effect, the nerve impulse is “shut off.” There are also receptors on the presynaptic neuron, termed autoreceptors, that can be stimulated by Ach to regulate and inhibit further neurotransmitter release from the neuron. The effects of the parasympathetic branch of the autonomic system on various organs are listed in Table 5-1. Drugs can mimic or block the action of the neurotransmitter Ach, to stimulate parasympathetic nerve ending sites (parasympathomimetics) or to block the transmission of such impulses (parasympatholytics). Both categories of drugs affecting the parasympathetic branch are commonly seen clinically. The effects of the parasympathetic system on the heart, bronchial smooth muscle, and exocrine glands should be mentally reviewed before considering parasympathetic agonists or antagonists (blockers):

Muscarinic and nicotinic receptors and effects

Two additional terms are used to refer to stimulation of receptor sites for Ach; they are derived from the action in the body of two substances, the alkaloids muscarine and nicotine. Receptor sites that are stimulated by these two chemicals are illustrated in Figure 5-4.

Muscarinic effects

! KEY POINT

Muscarinic refers to cholinergic receptors at parasympathetic end sites. Muscarinic receptors are distinguished into subtypes M₁ through M₅, with M₂ receptors in the heart and M₃ receptors on airway smooth muscle, mediating bronchoconstriction.

Muscarine, a natural product from the mushroom Amanita muscaria, stimulates Ach (cholinergic) receptors at the parasympathetic terminal sites: exocrine glands (lacrimal, salivary, and bronchial mucous glands), cardiac muscle, and smooth muscle (gastrointestinal tract). Ach receptors at these sites and the effects of parasympathetic stimulation at these sites are termed muscarinic. A muscarinic effect well known to respiratory care clinicians is the increase in airway secretions after administration of Ach-like drugs such as neostigmine. There is also a decrease in blood pressure caused by slowing of the heart and vasodilation. In general, a parasympathomimetic effect is the same as a muscarinic effect, and a parasympatholytic effect is referred to as an antimuscarinic effect.

Nicotinic effects

! KEY POINT

The term nicotinic refers to cholinergic receptors on ganglia and at the neuromuscular junction.

Nicotine, a substance in tobacco products, stimulates Ach (cholinergic) receptors at autonomic ganglia (parasympathetic and sympathetic) and at skeletal muscle sites. Ach receptors at autonomic ganglia and at the skeletal muscle are termed nicotinic, as are the effects on these sites of stimulation. Practical effects of stimulating these nicotinic receptors include an increase in blood pressure resulting from stimulation of sympathetic ganglia, causing vasoconstriction when the postganglionic fibers discharge, and muscle tremor caused by skeletal tissue stimulation.