Image for Cardiovascular Pharmacology Concepts, Richard E Klabunde PhD

Cardiovascular Pharmacology Concepts

Richard E. Klabunde, PhD

Clinical Disorders:

Therapeutic Classes:

Mechanism Classes:


Also Visit
CVphysiology.com


Cardiovascular Physiology Concepts textbook cover

Click here for information on Cardiovascular Physiology Concepts, 2nd edition, a textbook published by Lippincott Williams & Wilkins (2011)

 

Cardiovascular Physiology Concepts textbook cover

Click here for information on Normal and Abnormal Blood Pressure, a textbook published by Richard E. Klabunde (2013)





Atropine (Muscarinic Receptor Antagonist)

General Pharmacology

Image showing how ACh binds to muscarinic receptors (M2) found on cells of the sinoatrial (SA) and atrioventricular (AV) nodes on the heart; Muscarinic receptors are coupled to the Gi-protein; therefore, vagal activation decreases cAMP

The vagus (parasympathetic) nerves that innervate the heart release acetylcholine (ACh) as their primary neurotransmitter. ACh binds to muscarinic receptors (M2) that are found principally on cells comprising the sinoatrial (SA) and atrioventricular (AV) nodes. Muscarinic receptors are coupled to the Gi-protein; therefore, vagal activation decreases cAMP. Gi-protein activation also leads to the activation of KACh channels that increase potassium efflux and hyperpolarizes the cells.

Increases in vagal activity to the SA node decreases the firing rate of the pacemaker cells by decreasing the slope of the pacemaker potential (phase 4 of the action potential); this decreases heart rate (negative chronotropy). The change in phase 4 slope results from alterations in potassium and calcium currents, as well as the slow-inward sodium current that is thought to be responsible for the pacemaker current (If). By hyperpolarizing the cells, vagal activation increases the cell's threshold for firing, which contributes to the reduction the firing rate. Similar electrophysiological effects also occur at the AV node; however, in this tissue, these changes are manifested as a reduction in impulse conduction velocity through the AV node (negative dromotropy). In the resting state, there is a large degree of vagal tone on the heart, which is responsible for low resting heart rates.

There is also some vagal innervation of the atrial muscle, and to a much lesser extent, the ventricular muscle. Vagus activation, therefore, results in modest reductions in atrial contractility (inotropy) and even smaller decreases in ventricular contractility.

Muscarinic receptor antagonists bind to muscarinic receptors thereby preventing ACh from binding to and activating the receptor. By blocking the actions of ACh, muscarinic receptor antagonists very effectively block the effects of vagal nerve activity on the heart. By doing so, they increase heart rate and conduction velocity.

Specific Drugs and Therapeutic Indications

Atropine is a muscarinic receptor antagonist that is used to inhibit the effects of excessive vagal activation on the heart, which is manifested as sinus bradycardia and AV nodal block. Therefore, atropine can temporarily revert sinus bradycardia to normal sinus rhythm and reverse AV nodal blocks by removing vagal influences.

Side Effects and Contraindications

The anticholinergic effects of atropine can produce tachycardia, pupil dilation, dry mouth, urinary retention, inhibition of sweating (anhidrosis), blurred vision and constipation. However, most of these side effects are only manifested with excessive dosing or with repeated dosing. Atropine is contraindicated in patients with glaucoma.

Revised 03/15/07

DISCLAIMER: These materials are for educational purposes only, and are not a source of medical decision-making advice.