Atropine(Muscarinic+Receptor+Antagonist

__General Pharmacology__ 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.
 * Atropine (Muscarinic Receptor Antagonist****)**