Action potential, cardiac cells prolonging

Mechanism of action - Disopyramide is a class lA antiarrhythmic agent that decreases the rate of diastolic depolarization (phase 4), decreases the upstroke velocity (phase 0), increases the action potential duration of normal cardiac cells, and prolongs the refractory period (phases 2 and 3). It also decreases the disparity in refractoriness between infarcted and adjacent normally perfused myocardium and does not affect alpha- or beta-adrenergic receptors. 

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 ... 

It is an alkaloid obtained from the bark of cinchona and is a dextro isomer of anti-malarial drug quinine. Its sodium channel blocking property results in an increased threshold for excitability and decreased automaticity. As a consequence of its potassium channel blocking properties, it prolongs action potential in most cardiac cells. 

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 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). All these effects can be observed at therapeutic concentrations in the absence of overt toxicity (Table 13-2). 

In some types of rhythm disorders, antiar-rhythmics of the local anesthetic, Na+-channel blocking type are used for both prophylaxis and therapy. These substances block the Na+ channel responsible for the fast depolarization of nerve and muscle tissues. Therefore, the elicitation of action potentials is impeded and impulse conduction is delayed. This effect may exert a favorable influence in some forms of arrhythmia, but can itself act arrhythmogenically. Unfortunately, antiarrhythmics of the local anesthetic, Na+-channel blocking type lack suf -cient specificity in two respects (1) other ion channels of cardiomyocytes, such as K1 and Ca+ channels, are also affected (abnormal QT prolongation) and (2) their action is not restricted to cardiac muscle tissue but also impacts on neural tissues and brain cells. Adverse effects on the heart include production of arrhythmias and lowering of heart rate, AV conduction, and systolic force. CNS side effects are manifested by vertigo, giddiness, disorientation, confusion, motor disturbances, etc. 

Standard microelectrode techniques were used to study the effects of isocorydine on potential characteristics of canine cardiac Purkinje fibers and ventricular myocardium in vitro. In the Purkinje fibers, the action potential durations APDjj and APD were prolonged at 3 pmol/1 but shortened at 30 pmol/1 by isocorydine. The action potential amplitude and maximal upstroke velocity were decreased at 100 pmol/1. In the ventricular myocardium, the action potential characteristics were changed by isocorydine at concentrations above 30 pmol/1. The APDJ0 was shortened, the APD90 was prolonged, and the maximal upstroke velocity was decreased at 30 pmol/1. The effective refractory period was prolonged by the alkaloid in Purkinje fibers and ventricular myocardium. These results indicated that the alkaloid may interfere with K+, Na+, and Ca+2 currents in myocardial cell membranes at different concentrations [287]. 

Figure 14-7. Schematic diagram of the effects of ciass iV drugs in a calcium-dependent cardiac cell in the AV node (note that the AP upstroke is due mainly to calcium current). Class IV drugs reduce inward calcium current during the action potential and during phase 4 (wavy lines). As a result, conduction velocity is slowed in the AV node and refractoriness is prolonged. Pacemaker depolarization during phase 4 is slowed as well if caused by excessive calcium current.

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