The cholinoceptor antagonists are readily grouped into subclasses on the basis of their spectrum of action (ie, block of muscarinic versus nicotinic receptors). These drugs are pharmacologic antagonists or inverse agonists (eg, atropine). A special subgroup, the cholinesterase regenerators, are not receptor blockers but rather are chemical antagonists of organophosphate cholinesterase inhibitors.
|Anticholinergic||A drug that blocks muscarinic or nicotinic receptors, but commonly used to mean antimuscarinic|
|Antimuscarinic||A drug that blocks muscarinic but not nicotinic receptors|
|Atropine fever||Hyperthermia induced by antimuscarinic drugs; caused mainly by inhibition of sweating|
|Atropine flush||Marked cutaneous vasodilation of the arms and upper torso and head by antimuscarinic drugs; mechanism unknown|
|Cholinesterase regenerator||A chemical antagonist that binds the phosphorus of organophosphates and displaces acetylcholinesterase|
|Cycloplegia||Paralysis of accommodation; inability to focus on close objects|
|Depolarizing blockade||Flaccid skeletal muscle paralysis caused by persistent depolarization of the neuromuscular end plate|
|Miotic||A drug that constricts the pupil|
|Mydriatic||A drug that dilates the pupil|
|Nondepolarizing blockade||Flaccid skeletal muscle paralysis caused by blockade of the nicotinic receptor and prevention of end plate depolarization|
|Parasympatholytic, parasympathoplegic||A drug that reduces the effects of parasympathetic nerve stimulation, usually by blockade of the muscarinic receptors of autonomic effector tissues|
Classification and Pharmacokinetics
Classification of the Muscarinic Antagonists
Muscarinic antagonists can be subdivided according to their selectivity for specific M receptors or their lack of such selectivity. Although the division of muscarinic receptors into subgroups is well documented (Chapters 6 and 7), only 2 distinctly receptor-selective M1 antagonists have reached clinical trials (eg, pirenzepine, telenzepine). However, as noted later, several agents in use in the United States are somewhat selective for the M3 subtype. Most of the drugs in general use in the United States are relatively nonspecific. The muscarinic blockers can also be subdivided on the basis of their primary clinical target organs (central nervous system [CNS], eye, bronchi, or gastrointestinal and genitourinary tracts). Drugs used for their effects on the CNS or the eye must be sufficiently lipid-soluble to cross lipid barriers. A major determinant of this property is the presence or absence of a permanently charged (quaternary) amine group in the drug molecule because charged molecules are less lipid-soluble.
Atropine is the prototypical nonselective muscarinic blocker. This alkaloid is found in Atropa belladonna and many other plants. Because it is a tertiary amine, atropine is relatively lipid-soluble and readily crosses membrane barriers. The drug is well distributed into the CNS, the eye, and other organs. It is eliminated partially by metabolism in the liver and partially unchanged in the urine; half-life is approximately 2 h; duration of action of normal doses is 4–8 h except in the eye (see Drug Summary Table).
In ophthalmology, topical activity (the ability ...