McKenna's Pharmacology for Nursing, 2e

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P A R T 5  Drugs acting on the autonomic nervous system

The sympathetic response Perception of stress—Limbic system

Hypothalamus

SNS

ACTH

TSH

• ↑ BP • ↑ P • ↑ heart contraction • ↑ R • bronchodilation • pupil dilation • sweating • piloerection • glycogenolysis • blood to muscle • sphincter constriction • blood directed away from organs • ↓ GI activity and secretions

Cortisol

Aldosterone

↑ Thyroid levels ↑ Metabolism

↑ Na + retention ↑ water retention ↓ K +

↓ immune function ↓ inflammatory response ↑ glucose levels

↑ ADH release

↑ aldosterone ↑ BP

↑ blood volume

FIGURE 29.3  The “fight-or-flight” response: the sympathetic stress reaction. ACTH, adrenocorticotropic hormone; ADH, antidiuretic hormone; BP, blood pressure; GI, gastrointestinal; P, pulse; R, respiratory rate; SNS, sympathetic nervous system; TSH, thyroid-stimulating hormone.

↑ water retention

renin-angiotensin system activated

Alpha-receptors Alpha 1

building blocks necessary to produce noradrenaline (see Figure 29.4). Noradrenaline release When the nerve is stimulated, the action potential travels down the nerve axon and arrives at the axon terminal (see Chapter 19). The action potential then depolarises the axon membrane. This action allows calcium into the nerve, causing the membrane to contract and the storage vesicles to fuse with the cell membrane, releasing their load of noradrenaline into the synaptic gap or cleft. The noradrenaline travels across the very short gap to very specific adrenergic receptor sites on the effector cell on the other side of the synaptic gap. Adrenergic receptors Adrenergic receptors can be stimulated by the neuro- transmitter released from the axon in the immediate vicinity and they can be further stimulated by circulat- ing noradrenaline and adrenaline secreted directly into the bloodstream by the adrenal medulla. The receptor sites that react with neurotransmitters at adrenergic sites have been classified as alpha-receptors and beta- receptors . These receptors are further classified as alpha 1 ( a 1 )-, alpha 2 ( a 2 )-, beta 1 ( b 1 )- and beta 2 ( b 2 )- receptors (see Table 29.2). It is thought that receptors may respond to different concentrations of noradrena- line or different ratios of noradrenaline and adrenaline. Different drugs that are known to affect the SNS may affect parts of the sympathetic response, but not all of it, because they are designed to stimulate specific adren- ergic receptors.

-receptors are found in blood vessels, in the iris and in the urinary bladder. In blood vessels, they can cause vasoconstriction and increase peripheral resist- ance, thus raising blood pressure. In the iris, they cause pupil dilation. In the urinary bladder, they cause the increased closure of the internal sphincter. Alpha 2 -receptors are located on nerve mem- branes and act as modulators of noradrenaline release. When noradrenaline is released from a nerve ending, it crosses the synaptic cleft to react with its specific receptor site. Some of it also flows back to react with the alpha-receptor on the nerve membrane. This causes a reflex decrease in noradrenaline release. In this way, the alpha 2 -receptor helps to prevent overstimulation of effector sites. These receptors are also found on the beta cells in the pancreas, where they help to moderate the insulin release stimulated by SNS activation. Beta-receptors Beta 1 -receptors are found in cardiac tissue, where they can stimulate increasedmyocardial activity and increased heart rate. They are also responsible for increased lipolysis or breakdown of fat for energy in peripheral tissues. Beta 2 -receptors are found in the smooth muscle in blood vessels, in the bronchi, in the periphery and in uterine muscle. In blood vessels, beta 2 stimulation leads to vasodilation. Beta 2 -receptors also cause dilation in the bronchi. In the periphery, they can cause increased muscle and liver breakdown of glycogen and increased release of glucagon from the alpha cells of the pancreas. Stimulation of beta 2 -receptors in the uterus results in relaxed uterine smooth muscle.