Cardiac arrhythmias refractoriness

The effects of digitalis on the electrical properties of the heart are a mixture of direct and autonomic actions. Direct actions on the membranes of cardiac cells follow a well-defined progression an early, brief prolongation of the action potential, followed by a protracted period of shortening (especially the plateau phase). The decrease in action potential duration is probably the result of increased potassium conductance that is caused by increased intracellular calcium (see Chapter 14 Agents Used in Cardiac Arrhythmias). All of these effects can be observed at therapeutic concentrations in the absence of overt toxicity. Shortening of the action potential contributes to the shortening of atrial and ventricular refractoriness (Table 13-3). 

Cardiac arrhythmias ore caused by a disturbance in the con-duciion of the impulse through the myocardial tissue, bj disorders of impulse formation, or by a combination of ihete factors. The aniianhythmic agents used most commonly il-feet impulse conduction by altering conduction velocity aisl the duration of the refractory period of heart muscle lis iie They also depress spontaneous diastolic dcpolarizalim. causing a reduction of automaticity by ectopic foci. 

During Amy Lloyd s evalnation, she developed a cardiac arrhythmia that was refractory to treatment. The extensive amyloid deposits in her heart had disrupted conduction of electrical impulses in the heart muscle, ultimately resulting in cardiac arrest. On autopsy, amyloid deposits were found within the heart, tongue, liver, adipose tissue, and every organ examined except the central nervous system, which had been protected by the blood-brain barrier. 

B. Mitoxantrone This anthracene compound probably acts via the alkylation of DNA bases. Mi-toxantrone is used in combination regimens for refractory acute leukemia and in breast carcinoma. Myelosuppression, gastrointestinal effects, and cardiac arrhythmias are toxic effects of the drug. 

The toxicity of ephedrine is closely related to adverse cardiovascular events, since the clinical presentation of toxicity reflects the sympathomimetic activity of these agents. The adrenergic effects can shorten cardiac refractory periods, permitting the development of reentrant cardiac arrhythmias. The worst complication related to the use of ephedrine is thrombotic stroke, presumably resulting from vasoconstriction of large cerebral arteries that in turn leads to local thrombosis [71]. Other adverse effects include hypertension, diaphoresis, hypothermia, and agitation. The best treatment in an overdose is the rapid identification of the symptoms followed by supportive management. 

Uses Rapid conversion of AF/artmal fluto Action Class III antiarrhythmic Dose Adults >60 kg. 0.01 mg/kg (max 1 mg) IV inf over 10 min may repeat x 1 <60 kg Use 0.01 mg/kg (ECC 2005 D/C cardioversion preferred) Caution [C, -] Contra w/ class I/III antiarrhythmics (Table VI-7) QTc >440 ms Disp Inj SE Arrhythmias, HA Interactions t Refractory effects W7 amiodarone, disopyra-mide, procainamide, quinidine, sotalol t QT int val W7 antihistamines, antidepressants, erythromycin, phenothiazines, TCAs EMS Use antihistamines w/ caution, may T QT interval OD May cause increased repolarization leading to arrhythmias, bradycardia, hypotension leading to cardiac arrest symptomatic and supportive... 

Mechanism of Action A cardiac agent that prolongs duration of myocardial cell action potential and refractory period by acting directly on all cardiac tissue. Decreases AV and sinus node function. Therapeutic Effect Suppresses arrhythmias. Pharmacokinetics ... 

The antiarrhythmic action is due to cardiac adrenergic blockade. It decreases the slope of phase 4 depolarization and automaticity in SA node, Purkinje fibres and other ectopic foci. It also prolongs the effective refractory period of AV node and impedes AV conduction. ECG shows prolonged PR interval. It is useful in sinus tachycardia, atrial and nodal extrasystoles. It is also useful in sympathetically mediated arrhythmias in pheochromocytoma and halothane anaesthesia. 

Drugs that block beta-1 receptors on the myocardium are one of the mainstays in arrhythmia treatment. Beta blockers are effective because they decrease the excitatory effects of the sympathetic nervous system and related catecholamines (norepinephrine and epinephrine) on the heart.5,28 This effect typically decreases cardiac automaticity and prolongs the effective refractory period, thus slowing heart rate.5 Beta blockers also slow down conduction through the myocardium, and are especially useful in controlling function of the atrioventricular node.21 Hence, these drugs are most effective in treating atrial tachycardias such as atrial fibrillation.23 Some ventricular arrhythmias may also respond to treatment with beta blockers. 

Endogenous norepinephrine stimulates cardiac beta receptors. Receptor-linked cAMP-dependent protein kinases phosphorylate calcium channels to increase intracellular calcium. Elevated intracellular calcium increases conduction velocity (phase 0) and decreases the threshold potential in normal SA and AV node cells (see Figure 12.13). Beta blockers slow spontaneous conduction velocity in the SA node by approximately 10-20 percent. In addition, beta blockers can slow conduction velocity while increasing the refractory period of the AV node. These effects control the ventricular rate in atrial fibrillation or flutter and terminate paroxysmal supraventricular tachycardias. They are also safer, although somewhat less effective, than other drugs for suppression of premature ventricular complexes (PVCs). Drugs in this class approved by the FDA for treatment of various arrhythmias include propranolol, acebutolol, and esmolol. Problems with the beta blockers include drowsiness, fatigue, impotence, and depressed ventricular performance. 

Quinidine, the d-isomer of quinine, has been used in horses since 1924 (Roos 1924) and has a wide variety of properties. It is currently the drug of choice for the treatment of atrial fibrillation (AF) in horses but can be used for the treatment of a variety of re-entrant and ectopic arrhythmias. Quinidine affects heart rate, cardiac rhythm and vascular tone by a range of mechanisms and also produces a variety of non-cardiac effects. In addition to the class la activity, which prolongs the effective refractory period, the drug is vagolytic as a result of its antimuscarinic properties. 

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