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MNA Program
Fall 1999

Last updated 04/10/00 12:26 PM

4. Choose a Class I Na+ channel blocker. Explain its cellular mechanism(s) of action and how it may be potentially pro-arrhythmic. Include in your answer whether this blocker is selective for specific cells (e.g., for rapidly depolarizing cells or cells with long/short action potential durations), and how this property affects its efficacy and toxicity.

FLECANIDE is a class 1 antiarrhythmic. It slowly dissociates from the resting Na+ channel and shows prominent effects even at normal heart rates. These drugs are approved only for refractory arrhythmias.

ACTIONS: suppresses phase 0 upstroke in Purkinje fibers and myocardial fibers causes slowing of conduction in all cardiac tissue, with a minor effect on the duration of Action Potential (AP), and refractory period. Because 1A slow the rate of rise of AP, they slow conduction and prolong AP and increase the ventricular effective refractory period. They have an intermediate speed of association with activated/inactivated Na+ channels and an intermediate rate of dissociation from resting channels. Automaticity is reduced by an increase in the threshold potential, raises it to a less negative voltage decreased frequency of discharge.

Its a negative inotrope and its pro-arrhythmic. According to Stoelting , it has been difficult to demonstrate that antidysthrmic drugs alleviate symptoms related to CHRONIC dysrhythmias, a situation in which the risk of side effects is greater. The increase in long term mortality associated with certain cardiac antidysrrhymics drugs raises the possibility that some antidysrhythmics result in the sensitization of the myocardium to intercurrent triggering factors( myocardial ischemia, neuro-hormonal activation, myocardial stretch, slow healing post MI) can elicit cardiac dysrhythmias. Pro-arrhythmic events have been related to slowed AV conduction.

Flecainide works cells with long APs like Purkinje fibers & ventricular cells, and it does not cause EADs It also works on atrial tissue which has a shorter AP than PF & VCs. It prolongs PR, QRS, Q-T at normal heart rates.

Selectivity for specific cells, is what affects its efficacy and toxicity. This drug has a long recovery from Na+ channel block, which can exacerbate CHF in patients with decreased LVF. It can accelerate ventricular rate of patients with A flutter, increase the frequency of reentrant Vtach secondary to Na+ channel block. It can cause CHB in patients with conduction system disease. The Na+ block arrhythmia due to slowing of conduction. Whether a drug exacerbates or suppresses a re-entrant dysrhythmia depends on the balance between its effects on refractoryness and on conductance in a particular re-entrant circuit. Conduction slowing in potential re-entrant circuits can account for toxicity due to Na channel block, because it allows persistence of the reentrant wavefront with in the tachycardial circuit. Also there is increased AV nodal conduction through vagolytic action.

In a normal heart and with therapeutic concentrations minimal effects on automaticity and conduction velocity occur- thus describing its efficacy. At toxic concentrations flecanide can depress automaticity an conduction velocity a may therefore be arrhythmogenic.

References are Goodman, Brody, Lippincott, Stoelting

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