【正文】 ar rate ↓ (atrial fibrillation) Circulative blood flow volume ↑ (relive) sysptoms of heart failure ↓ ↓ ↓ ?In atrial fibrillation, the same vagomimetic action helps control ventricular rate, thereby improving ventricular filling and increasing cardiac output. ?Slowing conduction in AV node,increasing concealed conduction（隱匿性傳導(dǎo)） ,slowing ventricular rate. Concealed conduction ? The impulses arriving at the AV node are rapid and random in time. Most of these impulses either fail to enter the AV node because it is refractory or propagate only partway through it and give rise to the phenomenon of concealed conduction. 3. Atrial flutter atrial rate : 320~360 beats/min, rapid and regular In atrial flutter, the depressant effect of the drug on atrioventricular conduction will help control an excessively high ventricular rate. The effects of the drug on the atrial musculature may convert flutter to fibrillation, with a further decrease in ventricular rate Therapeutic action: (1)Increasing block and ERP in atrioventricular (AV) node heart rate decrease (ventricular rate) (2) Shortening ERP of atrium (convert) atrial flutter → atrial fibrillation (3) After withdrawal cardiac glycosides, sinus rhythm may return, ERP increase (prolong ERP of shortened ERP in atrium) (4) Quinidine may convert atrial flutter to sinus rhythm , but may increase the risk of cardiac glycosides toxicity. 3. Paroxysmal supraventricular tachycardia Increasing function of vagal nerve Enhance vagal activity Decrease excitation of atrium No use: supraventricular tachycardia caused by glycosidesintoxication Toxicity of cardiac glycosides 1. Gastrointestinal and centre nerve systom occasions sickness , vomiting , purging泄瀉 , giddiness眩暈 , confused vision , green vision or yellow vision , anorexia厭食 , nausea , diarrhea , abdominal disfort or pain , headache , fatigue the drugs may stimulate the chemoreceptor of trigger zone (CTZ) in the area postrema of the medulla(延髓極后區(qū)，化學(xué)感受區(qū)） 2. Toxic effects on the heart (1)Tachycardiac rhythm abnormalities (arrhythmia) Atrioventricular (AV) node Artial Ventricular fibrillation Bigeminy 二聯(lián)律 , trigeminy三聯(lián)律 } Tachycardia death machanism Severe inhibiting Na+K+ATPase Depletion of K+ in cell Resting potential or maximal diastolic potential Change small (negative value) (1)Automaticity easy to depolarization (2) Delaying after depolarization↑ 遲后去極化 ↓ ↓ ↓ } (2) AV block ★ the development of AV block is due in part to the vagal effect of glycosides Na+K+ATPase is strongly depressed Resting potential↓ Phase 0 depolarization rate ↓ Conduction slows ★ ↓ ↓ (3)Sinus bradycardia Sinus atrial node is depressed ↓ Automaticity ↓ Prevention of cardiac intoxication symptoms and signs Gastrointestinal effects Neurological effects Drug concentration in blood can be measured 2. Pathological situations Ion pH of blood Oxygen deficiency Age Drug interaction Treatment of cardiac glycosides introxication 1. Administration K+ , orally or iv 2. Administration of phenytoin treats severe tachycardiac rhythm abnormalities ventricular tachycardia bigeminy二聯(lián)律 recovering activity of enzyme ventricular tachycardia Ventricular fibrillation Lidocaine : } severe Atropine: Sinus bradycardia AV conduction block Administration 1 Digitalization ? Slow approach to “ digitalization” Is the safest dosing technique. ? Rapid approach to “digitalization” can be achieved quickly with a large loading dose (divided into three or four portions and given over 24~36 hours) followed by maintenance dose Thanks 2 Maintenance doses 3 Therapeutic method of Digoxin t1/2 36 hours mg/day 4~6 t1/2 (6~7 days) to approach steadystate level (Css)