Medical Pharmacology Chapter 6: Autonomic Pharmacology: Cholinergic Drugs
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.
This Web-based pharmacology teaching site is based on reference materials, that are believed reliable and consistent with standards accepted at the time of development. Possibility of human error and on-going research and development in medical sciences do not allow assurance that the information contained herein is in every respect accurate or complete. Users should confirm the information contained herein with other sources. This site should only be considered as a teaching aid for undergraduate and graduate biomedical education and is intended only as a teaching site. Information contained here should not be used for patient management and should not be used as a substitute for consultation with practicing medical professionals. Users of this website should check the product information sheet included in the package of any drug they plan to administer to be certain that the information contained in this site is accurate and that changes have not been made in the recommended dose or in the contraindications for administration. Advertisements that appear on this site are not reviewed for content accuracy and it is the responsibility of users of this website to make individual assessments concerning this information. Medical or other information thus obtained should not be used as a substitute for consultation with practicing medical or scientific or other professionals.