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Nursing Pharmacology Chapter 5: Autonomic Pharmacology: Cholinergic Drugs
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Direct vs. Indirect-Acting Cholinomimetics
A direct-acting cholinomimetic drug produces its pharmacological effect by receptor activation.
An indirect-acting drug inhibits acetylcholinesterase, thereby increasing endogenous acetylcholine levels, resulting in increased cholinergic response.
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Choline Ester |
Sensitivity to ACHE |
Cardiovascular |
Gastrointestinal |
Urinary Bladder |
Atropine Sensitive |
Activity at Nicotinic Sites |
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Acetylcholine |
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Methacholine |
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Carbachol |
No |
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Bethanechol (Urecholine) |
No |
? |
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No |
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Choline Ester Agent |
Sensitivity to ACHE |
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Acetylcholine (potentiated by AchE inhibitors) |
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Methacholine (potentiated by AchE inhibitors) |
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Carbachol (AchE inhibitors have no effect) |
No |
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Bethanechol (Urecholine) (AchE inhibitiors have no effect) |
No |
Pharmacological Effects of Cholinomimetics
Cardiovascular: Four major effects
This effect is mediated by muscarinic receptor activation and is especially prominent in the salivary gland and intestines. |
Vasodilation may also occur due to ACh inhibition of N.E. release from post-ganglionic sympathetic fibers.
Damaged endothelium can result in ACh causing vasoconstriction by direct action on vascular smooth muscle.
Negative chronotropic effect (Decrease in heart rate)
Decreases phase 4 (diastolic depolarization)
As a result, it takes longer for the membrane potential to reach threshold.
Mediated by M2 muscarinic receptors
Decreased SA nodal and AV nodal conduction velocity
Excessive vagal tone may induce bradyarrhythmias including partial or total heart block.
Impulses cannot pass through the AV node to drive the ventricular rate; in this case, the idioventricular or intrinsic ventricular rate must maintain adequate cardiac output.
Transmission through the AV node is especially dependent on Ca2+ currents.
ACh decreases calcium currents in the atrioventricular node.
Negative inotropism (decreased myocardial force of contraction (contractility))
This effect is more prominent in atrial than ventricular tissue and occurs because of a decrease in ICa2+ inward current
In the ventricle, adrenergic tone dominates.
At higher levels of sympathetic tone, a reduction in contractility due to muscarinic stimulation is noted.
Muscarinic stimulation reduces the response to norepinephrine by opposing increases in cAMP in addition to reducing norepinephrine release from adrenergic terminals.
Effect of muscarinic receptor activation on cardiac currents
(1) Muscarinic receptor activation causes an increase in I K (Ach) in atrial muscle and in SA and AV nodal tissue
(2) Muscarinic receptor activation results in a decrease in slow, inward calcium (ICa2+) current which reduces atrial contractility and decreases AV nodal impulse conduction.
(3) Muscarinic receptor activaiton decreases the heart pacemaker diastolic depolarizing current (If) thus decreasing heart rate. This effect occurs because it takes longer for the membrane potential to reach threshold since there is less depolarizing If current.
Gastrointestinal and Urinary Tracts
Muscarinic agonists increase intestinal peristalsis, tone, and contraction amplitude.
Carbachol and bethanecol (not ACh or methacholine) stimulate the urinary tract by increasing ureteral peristalsis and by contraction of the urinary bladder detrusor muscle.
Brown, J.H. and Taylor, P. Muscarinic Receptor Agonists and Antagonists, In, Goodman and Gillman's The Pharmacological Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGraw-Hill Companies, Inc.,1996, pp.149-150
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