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(2) Negative chronotropic effects Reflex inhibition of sympathetic activity cardiac output ? ? Sympathetic activity ? ? HR ? Increasing vagal activity directly Reducing AV conduction: ventricular rate ? E. Cardiac glycoside (digitalis) (3) Electrophysiological effects decreasing automaticity of sinoatrial node slow conduction, especially AV conduction increasing automaticity of Purkinje fibres shortening ERP of fast response cells Mechanisms: intracellular Na+ ?, K+ ?, Ca2+ ?? ? MDP ?, afterdepolarization E. Cardiac glycoside (digitalis) Overdose: Na+ ?, K+ ?, Ca2+ ? ? ? MDP ? ? afterdepolarization Electrophysiological basis for digitalis overdose ECG: P-R ?; S-T/T wave ?; various arrhythmias P-R ? S-T/T wave ? prematural ventricular beat (4) Other effects Vessels: vasoconstriction Central nervous system: CTZ dopamine D2 receptor mental and vision disorders Kidney increase blood supply of kidney diuretic effect: decrease Na+ reabsorption E. Cardiac glycoside (digitalis) 2. Clinical uses (1) Congestive heart failure (CHF) especially associated with atrial fibrillation and sinus tachycardia (2) Arrhythmias atrial fibrillation / atrial flutter: paroxysmal surpraventricular tachycardia E. Cardiac glycoside (digitalis) 3. Adverse effects (1) Gastrointestinal effects nausea, vomiting, etc. (2) CNS effects alteration of color perception（色视, such as yellow vision 黄视）; headache, fatigue, confusion, etc. E. Cardiac glycoside (digitalis) (3) Cardiac toxicity arrhythmias：prematural beats, tachycardia， atrioventricular block, sinus bradycardia, etc. Prevention：Dose individualization Avoiding provocation factors: plasma K+ ?, and drug interactions, etc. Treatment： KCl, phenytoin or lidocaine, i.v. Atropine: A-V block, sinus bradycardia