Acetylcholine autonomic pharmacology

Choline esters are poorly absorbed and poorly distributed into the central nervous system because they are hydrophilic. Although all are hydrolyzed in the gastrointestinal tract (and less active by the oral route), they differ markedly in their susceptibility to hydrolysis by cholinesterase in the body. Acetylcholine is very rapidly hydrolyzed (see Chapter 6 Introduction to Autonomic Pharmacology) large amounts must be infused intravenously to achieve concentrations high enough to produce detectable effects. A large intravenous bolus injection has a brief effect, typically... 

The primary cardiovascular effects of muscarinic agonists are reduction in peripheral vascular resistance and changes in heart rate. The direct effects listed in Table 7-3 are modified by important homeostatic reflexes, as described in Chapter 6 Introduction to Autonomic Pharmacology and depicted in Figure 6-7. Intravenous infusions of minimal effective doses of acetylcholine in humans (eg, 20-50. g/min) cause vasodilation, resulting in a reduction in blood pressure, often accompanied by a reflex increase in heart rate. Larger doses of acetylcholine produce bradycardia and decrease atrioventricular node conduction velocity in addition to the hypotensive effect. 

Fig. 12.8. General cholinergic nerve junction showing location of receptor sites and biosynthesis, storage, release, and hydrolysis of acetylcholine. (Katzung BG. Introduction to autonomic pharmacology. In Katzung BG, ed. Basic and Clinical Pharmacology, 9th Ed. New York McGraw-Hill, 2004, pp. 75-93 with permission.)...

Carbachol is a powerful cholinic ester that stimulates both muscarinic and nicotinic receptors, as well as exhibits all of the pharmacological properties of acetylcholine while in addition resulting in vasodilation, a decrease in heart rate, an increase in tone and con-tractability of smooth muscle, stimulation of salivary, ocular, and sweat glands as well as autonomic ganglia and skeletal muscle. For this reason, use of carbachol, like acetylcholine, is limited. The exception is that it is used in ophthalmological practice and post-operational intestines and bladder atony. Upon administration in the eye, the pupil constricts and the intraocular pressure is reduced. It is used for severe chronic glaucoma. Synonyms of this drag are doryl and miostat. 

Pharmacology Nicotine, the chief alkaloid in tobacco products, binds stereo-selectively to acetylcholine receptors at the autonomic ganglia, in the adrenal medulla, at neuromuscular junctions, and in the brain. 

The action of acetylcholine at the skeletal muscle motor end plate resembles that produced by nicotine. Thus, the choUnoreceptor on skeletal muscle is a nicotinic receptor. Based on antagonist selectivity, however, the autonomic and somatic nicotinic receptors are not pharmacologically identical (see Chapter 14). 

Nature is economical in her means. She uses many of the same chemicals to accomplish her nervous purposes within the brain that she has already used to the same ends throughout the body. The good news is that once you have worked out the biochemistry and pharmacology of a neuromodulator in the body, you can apply a lot of what you know to its action in the brain. The bad news is that every time you target, for example, the acetylcholine system of the brain, you also hit the body. That means that the heart, the bowel, the salivary glands, and all the rest of the organs innervated by the autonomic nervous system are influenced. What is worse, the target sites within the brain may not only be as spatially dispersed as in the periphery, but may also be as functionally differentiated ... 

Figure 6-1. Schematic diagram comparing some features of the parasympathetic and sympathetic divisions of the autonomic nervous system with the somatic motor system. Parasympathetic ganglia are not shown as discrete structures because most of them are diffusely distributed in the walls of the organs innervated. ACh, acetylcholine Epi, epinephrine NE, norepinephrine, D, dopamine N, nicotinic M, muscarinic a, p, alpha and beta adrenoceptors D, dopamine, receptors. (Reproduced, with permission, from Katzung BG [editor] Basic Clinical Pharmacology, 8th ed. McGraw-Hill, 2001.)...

---