One group of cholinergic antagonists has already been discussed: the nondepolarizing neuromuscular-blocking agents. These drugs act primarily at the nicotinic receptors in skeletal muscle. This chapter presents the pharmacology of drugs that block muscarinic receptors. Although the classification anticholinergic usually refers to this latter group, a more precise term would be antimuscarinic.
In this chapter, the mechanism of action and clinical pharmacology are introduced for three common anticholinergics: atropine, scopolamine, and glycopyrrolate. The clinical uses of these drugs in anesthesia relate to their effect on the cardiovascular, respiratory, cerebral, gastrointestinal, and other organ systems (Table 13-1).
Table 13-1 Pharmacological Characteristics of Anticholinergic Drugs.1 |Favorite Table|Download (.pdf)
Table 13-1 Pharmacological Characteristics of Anticholinergic Drugs.1
Anticholinergics are esters of an aromatic acid combined with an organic base (Figure 13-1). The ester linkage is essential for effective binding of the anticholinergics to the acetylcholine receptors. This competitively blocks binding by acetylcholine and prevents receptor activation. The cellular effects of acetylcholine, which are mediated through second messengers, are inhibited. The tissue receptors vary in their sensitivity to blockade. In fact, muscarinic receptors are not homogeneous, and receptor subgroups have been identified including: neuronal (M1), cardiac (M2), and glandular (M3) receptors.
Physical structures of anticholinergic drugs.
General Pharmacological Characteristics
In normal clinical doses, only muscarinic receptors are blocked by the anticholinergic drugs discussed in this chapter. The extent of the anticholinergic effect depends on the degree of baseline vagal tone. Several organ systems are affected.
Blockade of muscarinic receptors in the sinoatrial node produces ...