Study Set Content:
First clinical description by-
Thomas Willis in 1672
is the most frequent early sign of myasthenia gravis, a disease that produces extensive muscle weakness
A drooping eyelid
Because the primary action is to amplify the actions of endogenous acetylcholine, the effects are similar (but not always identical to the effects of the
direct-acting cholinomimetic agonists.
In low concentrations, the lipid soluble cholinesterase inhibitors cause
diffuse activation.
In higher concentrations, they cause generalized convulsions, which may be followed by
coma and respiratory arrest
similar to the effects of the direct-acting cholinomimetics.
Eyes, respiratory tract, GI tract, urinary
The cholinesterase inhibitors can (blank) activity in both sympathetic and parasympathetic ganglia supplying the heart and at the acetylcholine receptors on neuro effector cells (cardiac and vascular smooth muscles) that receive cholinergic innervation.
increase
mimic the effects of vagal nerve activation on the heart
Edrophonium, physostigmine, or neostigmine
Negative chronotropic, dromotropic,
and inotropic effects are produced, and cardiac output
falls
(blank), (blank) atrial contractility, and some (blank) in ventricular contractility.
Bradycardia, decreased, reduction
moderately prolong and intensify the actions of physiologically released acetylcholine. This increases the strength of contraction, especially in muscles weakened by curare-like neuromuscular blocking agents or by myasthenia gravis
Low (therapeutic) concentrations
the accumulation of acetylcholine may result in fibrillation of muscle fibers
higher concentrations
have an additional direct nicotinic agonist effect at the neuromuscular junction.
neostigmine
This may contribute to the effectiveness of these agents as therapy for
myasthenia.
INDIRECT-ACTING CHOLINERGIC ANTAGONISTS: Examples:
Isoflurophate
Echothiophate
Parathion
Edrophonium
Physostigmine
Neostigmine
How do they work?
By inhibiting the enzyme _____, which is responsible for the hydrolysis of acetylcholine. Neuronal response to acetylcholine is therefore enhanced.
acetylcholinesterase
Which indirect-acting cholinergic agonists have the ability to irreversibly inhibit acetylcholinesterase?
Only the organophosphates such as _____ irreversibly inhibit acetylcholinesterase
Isoflurophate, Echothiophate, & Parathion
Why are Physostigmine, Neostigmine, Edrophonium, Pyridostigmine considered to be reversible?
Because they do not bind _____ to acetylcholinesterase.
covalently
CLINICAL PHARMACOLOGY OF THE CHOLINOMIMETICS
Major therapeutic uses:
To treat diseases of the _____ (glaucoma, accommodative esotropia)
eye
(postoperative atony, neurogenic bladder
gastrointestinal and urinary tracts
