The ester linkage is essential for effective binding of anticholinergics to acetylcholine receptors. This binding competitively blocks binding by acetylcholine and prevents receptor activation. The cellular effects of acetylcholine, which are mediated through second messengers, are inhibited.
Anticholinergics relax the bronchial smooth musculature, which reduces airway resistance and increases anatomic dead space.
Atropine has particularly potent effects on the heart and bronchial smooth muscle and is the most efficacious anticholinergic for treating bradyarrhythmia.
Ipratropium solution (0.5 mg in 2.5 mL) seems to be particularly effective in the treatment of acute chronic obstructive pulmonary disease when combined with a β-agonist drug (eg, albuterol).
Scopolamine is a more potent antisialagogue than atropine and causes greater central nervous system effects.
Because of its quaternary structure, glycopyrrolate cannot cross the blood–brain barrier and is almost devoid of central nervous system and ophthalmic activity.
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 13–1Pharmacological characteristics of anticholinergic drugs.1 ||Download (.pdf) TABLE 13–1 Pharmacological characteristics of anticholinergic drugs.1
| ||Atropine ||Scopolamine ||Glycopyrrolate |
|Tachycardia ||+++ ||+ ||++ |
|Bronchodilatation ||++ ||+ ||++ |
|Sedation ||+ ||+++ ||0 |
|Antisialagogue effect ||++ ||+++ ||+++ |
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, mediated through second messengers, are inhibited. Muscarinic receptors are not homogeneous, and receptor subgroups have been identified, including central nervous system (M1,4,5), autonomic ganglia and gastric parietal cells (M1), cardiac (M2), and smooth muscle (M3) receptors. These receptors vary in their affinity for receptor antagonists.
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 clinical response to an anticholinergic drug depends on the degree of baseline vagal tone.