Study Set Content:
bind to and activate muscarinic or nicotinic receptors
Direct-acting cholinomimetic agents
The direct-acting cholinomimetic drugs can be divided on the basis of chemical structure into:
1. esters of choline
2. alkaloids
(including acetylcholine)
esters of choline
(such as muscarine and nicotine).
alkaloids
produce their primary effects by inhibiting acetylcholinesterase, which hydrolyzes acetylcholine to choline and acetic acid.
Indirect-acting agents
(blank) important choline esters that have been studied extensively
Four
Their permanently charged quaternary ammonium group renders them relatively (blank) in lipids
insoluble
are poorly absorbed and poorly distributed into the central nervous system because they are hydrophilic.
Choline esters
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
is very rapidly hydrolyzed
Acetylcholine
has a brief effect, typically 5-20 seconds
Large intravenous bolus injection
whereas intramuscular and subcutaneous injections produce only
local effects
is more resistant to hydrolysis
Methacholine
are still more resistant to hydrolysis by cholinesterase and have correspondingly longer durations of action.
Carbamic acid esters carbachol and bethanechol
reduces the potency of these drugs at nicotinic receptors.
β-methyl group (methacholine, bethanechol)
are well absorbed from most sites of administration.
pilocarpine, nicotine, lobeline
, a liquid, is sufficiently lipid-soluble to be absorbed across the skin.
Nicotine,
is less completely absorbed from the gastrointestinal tract but is nevertheless toxic when ingested
Muscarine
is a plant derivative similar to nicotine. These amines are excreted chiefly by the kidneys.
Lobeline
Acidification of the urine accelerates clearance of the
tertiary amines
