cardiology2016 151-160

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 become 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 effects of class 1C drugs can cause a delay in conduction speed that is out of proportion to prolongation of the refractory period. This can promote arrhythmias, especially in patients with ischemic or structural heart disease. Class 1B antiarrhythmics (eg, lidocaine, mexiletine, and tocainide) bind less avidly to sodium channels than the other class 1 antiarrhythmics (Choice D). Dissociation from the channels occurs so rapidly that there is minimal cumulative effect over multiple cardiac cycles, resulting in little use dependence. These drugs are more selective for ischemic myocardium because the reduced resting membrane potential delays sodium channel transition from the inactivated to the resting state, resulting in increased drug-channel binding. Class 1B antiarrhythmics are useful for treating ischemia-induced ventricular arrhythmias, one of the most common causes of death in the short term following acute myocardial infarction. (Choice A) Amiodarone is classified primarily as a class 3 antiarrhythmic medication although it has small class 1, 2? and 4 effects as well. The class 3 antiarrhythmics act by blocking potassium channels and prolonging phase 3 repolarization. (Choice B) Disopyramide, quinidine, and procainamide are class 1A antiarrhythmic dmgs. They are represented by line 2 on the graph because of their intermediate dissociation speed. (Choice C) Propafenone and flecainide are class 1C antiarrhythmic drugs. They are represented by line 3 on the graph because of their slow dissociation speed. (Choice E) Propranolol (a nonselective (3-adrenergic blocker) is categorized as a class 2 antiarrhythmic drug. It causes decreased chronotropy and inotropy via (31 blockade. (Choice F) Verapamil as a calcium channel blocker is classified as a class IV antiarrhythmic drug; diltiazem is another drug in this class. Although nifedipine is a calcium channel blocker as well, it is selective for vascular smooth muscle and does not have a notable effect on the heart. Educational objective: Use dependence describes the phenomenon in which higher rates of depolarization lead to increased sodium channel blockade due to the channels spending less time in the resting state. For class 1 antiarrhythmics, sodium-channel-binding strength is 1C>1A>1B. Class 1C antiarrhythmics demonstrate the most use dependence, and class 1B drugs have the least
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A 48-year-old man comes to the office for a follow-up visit. He was diagnosed with hypercholesterolemia 6 months ago and has been strictly following dietary and lifestyle modifications as advised. The patient has no other medical problems. He does not use tobacco, alcohol, or illicit drugs. His father has diabetes mellitus and coronary artery disease. The patient's blood pressure is 126/70 mm Hg and BMI is 33.1 kg/㎡. Physical examination is normal. Laboratory studies show a current LDL level of 190 mg/dL. Which of the following should be obtained before starting statin therapy in this patient? A. Apolipoprotein-B level B. Complete blood count C. Lipoprotein lipase activity assay D. Liver transaminase levels E. Serum cortisol level F. Serum creatinine