Category: Fundamentals ACE inhibitors act on the ACE enzyme that generates angiotensin II from angiotensin I and inactivates the breakdown of bradykinin. Angiotensin I originates in the liver from angiotensinogen under the influence of the enzyme renin.
Category: Fundamentals Calcium channel blockers have many important drug interactions. Diltiazem and verapamil interact with digoxin and cyclosporine, among others. They increase digoxin levels and increase plasma levels of cyclosporine.
Category: Fundamentals Nondihydropyridine calcium channel blockers are contraindicated in patients with bradycardia, sick sinus syndrome or more advanced heart block (in the absence of a pacemaker). Caution must be used in patients with atrial tachyarrhythmias.
Category: Fundamentals Higher doses of dihydropyridine calcium channel blockers often result in some degree of edema, and can additionally cause flushing, headache and tachycardia. Lower extremity edema is the most commonly observed of these side effects.
Category: Fundamentals Calcium channel blockers act primarily to reduce peripheral vascular resistance and, within the renal vasculature, produce natriuresis by increasing renal blood flow, dilating afferent arterioles and increasing glomerular filtration pressure.
Category: Fundamentals Calcium channel blockers impede the movement of extracellular calcium through ion-specific channels within the cell wall. This ultimately reduces calcium flux inward, which results in arterial dilation via smooth muscle relaxation.
Category: Fundamentals Metolazone is a powerful thiazide diuretic with a quinazoline structure. An important advantage of metolazone is efficacy even despite decreased kidney function and is usually used in concert with loop diuretics for edema management.
Category: Fundamentals Thiazide-like and thiazide diuretics can be very different pharmacokinetically. Compared to hydrochlorothiazide, chlorthalidone has a considerably longer half-life, approximately 40-60 hours and a larger volume of distribution.
Category: Fundamentals Among thiazide-type diuretics, hydrochlorothiazide is the most widely used. It has a bioavailability ranging from 60% to 80%. Its absorption may be decreased in heart failure and/or chronic kidney disease.
Category: Fundamentals Thiazide-type diuretics as a class differ from the loop diuretics in that they have a longer duration and site of action. Additionally, thiazides are so-called low-ceiling diuretics, because the maximal response is reached at a relatively low dose.
Category: Fundamentals Loop diuretics, including the most commonly used furosemide and torsemide, inhibit the Na+/K+/2Cl- cotransporter associated with the transport of chloride across the lining cells of the ascending limb of the loop of Henle.
Category: Fundamentals Thiazide-type diuretics inhibit the reabsorption of sodium and chloride in the more distal part of the nephron. This distal cotransporter is insensitive to loop diuretics. Oral formulations produce a diuresis within 1 to 2 hours.
Category: Fundamentals Diuretics alter physiologic renal mechanisms to increase the flow of urine with greater excretion of sodium or natriuresis. This results in a wide range of effects on BP. Moreover, thiazide-type diuretics also result in mild vasodilation.
Category: Fundamentals Ranolazine reduces angina without any significant reductions in heart rate, BP, or rate-pressure product during exercise and is hemodynamically neutral, thus making it a useful therapeutic option in patients who are at risk of hypotension.
Category: Fundamentals Ranolazine is an inhibitor of sodium channel influx during repolarization. This reduces intracellular sodium concentrations, which, in turn, results in a reduction in oxygen consumption and improvement in angina symptoms.
