Atropine (Muscarinic Receptor Antagonist)
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 at 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 the 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 in firing rate. Similar electrophysiological effects also occur at the AV node; however, in this tissue, these changes are manifested as a reduction in the velocity of impulse conduction through the AV node (negative dromotropy). In the resting state, there is a large degree of vagal tone acting 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. Vagal activation, therefore, results in modest reductions in atrial contractility (inotropy) and even smaller decreases in ventricular contractility.
Muscarinic receptor antagonists bind to muscarinic receptors, preventing ACh from binding to and activating the receptor. By blocking the actions of ACh, muscarinic receptor antagonists effectively block the effects of vagal nerve activity on the heart. By doing so, they increase heart rate (SA node) and conduction velocity (AV node).
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 a normal sinus rate and reverse AV nodal blocks by removing vagal influences. Atropine is administered intravenously.
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.