cardiology2016 151-160.ppt

cardiology2016
151-160
Q 1
A new drug has been developed to treat cardiac arrhythmias. The drug has high affinity for activated and inactivated sodium channels but relatively little affinity for resting sodium channels. An experiment is devised to maintain sodium channels in the inactivated state for a prolonged period, during which they are exposed to the new drug. After allowing the sodium channels to return to the resting state, the speed of the drug's dissociation from the sodium channels is recorded and shown below (line 1). The dissociation curve for quinidine is given parison (line 2).
The pharmacologic action of the new drug is most similar to which of the following drugs?
A. Amiodarone
B. Disopyramide
C. Flecainide
D. Lidocaine
E. Propranolol
F. Verapamil
A 1
Correct answer:D
The drug described is representative of a class 1 antiarrhythmic medication. These drugs preferentially bind to and block activated and inactivated voltage-gated sodium channels in cardiac pacemaker cells and myocytes. Dissociation of the drug from the channel occurs during the resting state, a conformational state distinct from the inactivated state that occurs following repolarization. Class 1 antiarrhythmics exhibit use dependence, a phenomenon in which tissues undergoing frequent depolarization e more susceptible to blockage. Use dependence occurs because the sodium channels in rapidly depolarizing tissue spend more time in the activated and inactivated states, thus allowing more binding time for the drug.
For class 1 antiarrhythmics. sodium-channel-binding strength is 1C > 1A > 1B. Use dependence is more pronounced in class 1C antiarrhythmics because of their slow dissociation from the sodium channel, which allows their blocking effects to accumulate over multiple cardiac cycles. This effect is enhanced with tachycardia, and the resulting increase in sodium channel blockade helps to slow conduction speed and terminate tachyarrhythmias. The prominent use dependence effec