Drugs with acetylcholine-like effects (cholinomimetics) consist of 2 major subgroups on the basis of their mode of action (ie, whether they act directly at the acetylcholine receptor or indirectly through inhibition of cholinesterase). Drugs in the direct-acting subgroup are further subdivided on the basis of their spectrum of action (ie, whether they act on muscarinic or nicotinic cholinoceptors).
Acetylcholine may be considered the prototype that acts directly at both muscarinic and nicotinic receptors. Neostigmine is a prototype for the indirect-acting cholinesterase inhibitors.
DIRECT-ACTING CHOLINOMIMETIC AGONISTS
This class comprises a group of choline esters (acetylcholine, methacholine, carbachol, bethanechol) and a second group of naturally occurring alkaloids (muscarine, pilocarpine, nicotine, lobeline). Newer drugs are occasionally introduced for special applications. The members differ in their spectrum of action (amount of muscarinic versus nicotinic stimulation) and in their pharmacokinetics (Table 7–1). Both factors influence their clinical use.
High-Yield Terms to Learn
|Choline esters ||A cholinomimetic drug consisting of choline (an alcohol) or a choline derivative, esterified with an acidic substance (eg, acetic or carbamic acid); usually poorly lipid-soluble |
|Cholinergic crisis ||The clinical condition of excessive activation of cholinoceptors; it may include skeletal muscle weakness as well as parasympathetic effects, usually caused by cholinesterase inhibitors; cf myasthenic crisis |
|Cholinomimetic alkaloids ||A drug with weakly alkaline properties (usually an amine of plant origin) whose effects resemble those of acetylcholine; usually lipid-soluble |
|Cyclospasm ||Marked contraction of the ciliary muscle; maximum accommodation for close vision |
|Direct-acting cholinomimetic ||A drug that binds and activates cholinoceptors; the effects mimic those of acetylcholine |
|Endothelium-derived relaxing factor (EDRF) ||A potent vasodilator substance, largely nitric oxide (NO), that is released from vascular endothelial cells |
|Indirect-acting cholinomimetic ||A drug that amplifies the effects of endogenous acetylcholine by inhibiting acetylcholinesterase |
|Muscarinic agonist ||A cholinomimetic drug that binds muscarinic receptors and has primarily muscarine-like actions |
|Myasthenic crisis ||In patients with myasthenia, an acute worsening of symptoms; usually relieved by increasing cholinesterase inhibitor treatment; cf cholinergic crisis |
|Nicotinic agonist ||A cholinomimetic drug that binds nicotinic receptors and has primarily nicotine-like actions |
|Organophosphate ||An ester of phosphoric acid and an alcohol that inhibits cholinesterase |
|Organophosphate aging ||A process whereby the organophosphate, after binding to cholinesterase, is chemically modified and becomes more firmly bound to the enzyme |
|Parasympathomimetic ||A drug whose effects resemble those of stimulating the parasympathetic nerves |
TABLE 7–1Some cholinomimetics: spectrum of action and pharmacokinetics. ||Download (.pdf) TABLE 7–1 Some cholinomimetics: spectrum of action and pharmacokinetics.
|Drug ||Spectrum of Actiona ||Pharmacokinetic Features |
|Direct-acting || || |
| Acetylcholine ||B ||Rapidly hydrolyzed by cholinesterase (ChE); duration of action 5–30 s; poor lipid solubility |
| Bethanechol ||M ||Resistant to ChE; orally active, poor lipid solubility; duration of action 30 min to 2 h |
| Carbachol ||B ||Like bethanechol |
| Pilocarpine ||M ||Not an ester, good lipid solubility; duration of action 30 ...|