Grug Therapy: ACE Inhibitors
Angiotensin-converting enzyme (ACE) inhibitors lower blood pressure by blocking the conversion of angiotensin I to the potent vasoconstrictor, angiotensin II, and reducing the secretion of the volume-retaining hormone aldosterone. Captopril can also act by increasing levels of vasodilator bradykinins and prostaglandins. Captopril and enalapril have similar effectiveness; both are usually well tolerated with few quality of life concerns. Both are eliminated renally and can cause renal failure.
Patients with high peripheral renin activity (those with depleted intravascular volume, those on diuretics, and those with renovascular hypertension) may have an excess fall in blood pressure with initial doses. Initial doses should therefore be small. These agents can produce renal failure in patients whose glomerular filtration rate depends on maintenance of (angiotensin II dependent) efferent arteriolar tone (that is, patients with bilateral renal artery stenosis or renal artery stenosis in a solitary functioning kidney). Angiotensin-converting enzyme inhibitors can, however, be of benefit to patients with diabetic nephropathy; they can diminish the rate of urinary protein excretion by reducing glomerular capillary hydrostatic pressure.
Side effects that may limit the usefulness of angiotensin-converting enzyme (ACE) inhibitors include rash, ageusia, and dry, hacking cough (thought to be secondary to direct stimulation of pharyngeal nerve receptors or increased bradykinin levels leading to occult bronchospasm). Leukopenia and proteinuria are rarely seen at currently recommended doses. Enalapril may cause fewer skin problems and taste disturbances than captopril.
Angiotensin-converting enzyme inhibitors are weakly potassium sparing and may promote the development of hyperkalemia in patients with a reduced capacity to excrete potassium (diabetes with type IV renal tubular acidosis, renal insufficiency).
Enalapril has a longer duration of action than captopril and may be taken once daily; it is also less expensive than captopril.
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