USMLE STEP 3 MCQ 31 :A patient with chronic hypertension


A patient with chronic hypertension is on treatment with nifedipine, a calcium channel blocker.
Nifedipine lowers the blood pressure mainly by inhibiting the influx of extracellular calcium through the calcium channel of


a) skeletal muscle cells
b) smooth muscle cells
c) myocardial cells
d) cells in the atrioventricular (AV) node
e) cells in the sinoatrial (SA) node

Correct Answer: B


The selective calcium channel blockers share a similar antihypertensive mechanism of action: they inhibit the influx of extracellular calcium through the L-type channel, resulting in relaxation of vascular smooth muscle and reduction in vascular resistance. They are therefore often assumed to be a homogeneous family of drugs, whereas they are in fact an extremely heterogeneous group of compounds with marked differences in chemical structure, binding sites, tissue selectivity, and, consequently, clinical activity and therapeutic indication.  Selective calcium channel blockers include three discrete chemical types: the phenylalkylamines (eg, verapamil), the benzothiazepines (eg, diltiazem), and the 1,4-dihydropyridines (eg, nifedipine)  Binding sites for all three types of calcium channel blocker are found in a variety of tissues, including myocardium, smooth muscle, skeletal muscle, and glandular tissue. Yet this range of target tissues is not necessarily reflected in pharmacologic or therapeutic activity. For example, skeletal smooth muscle is relatively insensitive to calcium channel blockade, as indicated by the fact that calcium channel blocker therapy does not interfere with postural tone.Like other calcium-channel antagonists, nifedipine inhibits the influx of extracellular calcium through myocardial and vascular membrane pores, which are selective for specific ions. Serum calcium levels remain unchanged. It is believed that nifedipine inhibits this influx by physically plugging the channel. While verapamil and diltiazem exert balanced effects on calcium channels in the SA node, AV node, and vasculature, nifedipine and other members of the dihydropyridine group act predominantly on the vasculature, making these agents more potent peripheral vasodilators. The decrease in intracellular calcium inhibits the contractile processes of smooth muscle cells, causing dilation of the coronary and systemic arteries. This results in increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.In the past 15 to 20 years, numerous calcium channel blockers (CCBs) have been introduced. The CCBs lower blood pressure by inhibiting the entry of calcium ions into vascular smooth muscle cells, which:  Reduces vascular tone and contractility  Results in vasodilation  Reduces peripheral resistance  Decreases blood pressure There are several types of CCBs. The nondihydropyridines diltiazem (Cardizem CD and SR, Dilacor XR, Tiazac), and verapamil (Calan SR, Isoptin SR, Verelan, Covera-HS) act on heart muscle as well as peripheral arterioles. Another type of CCB, mibefradil (Posicor) which acted to block calcium entry into cells through a different mechanism (T-channel blockers) has been withdrawn from the market because of numerous interactions with other drugs. Some CCBs, especially the verapamil type, may result in partial blockade of the atrioventricular (AV) or sinoatrial (SA) node, as well as have a negative inotropic effect

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