Angiotensin-converting enzyme clinical effects

Azathioprine, mycophenolate mofetil, and enteric-coated MPA are not metabolized through the CYP isozyme system therefore, they do not experience the same DDI profiles as cyclosporine, tacrolimus, and sirolimus. Azathioprine s major DDIs involve allopurinol, angiotensin-converting enzyme (ACE) inhibitors, aminosalicylates (e.g., mesalamine and sulfasalazine), and warfarin.11 The interaction with allopurinol is seen frequently and has clinical significance. Allopurinol inhibits xanthine oxidase, the enzyme responsible for metabolizing azathioprine. Combination of azathioprine and allopurinol has resulted in severe toxicities, particularly myelosuppression. It is recommended that concomitant therapy with azathioprine and allopurinol be avoided, but if combination therapy is necessary, the azathioprine doses must be reduced to one-third or one-fourth of the current dose. Use of azathioprine with the ACE inhibitors or aminosalicylates also can result in enhanced myelosuppression.11 Some case reports exist demonstrating that warfarin s therapeutic effects may be decreased by azathioprine.43-45... 

Clinical effects Angiotensin-converting enzyme inhibitors improve symptoms, New York Heart Association (NYHA) functional class, and exercise capacity in patients with HF The Captopril Multicenter Research Group (6) showed that captopril treatment improved the NYHA class in 61% of patients compared with only 24% of patients taking placebo over a 12-week period, Treadmill exercise time improved throughout the 12 weeks of the study in 24% of captopril-treated patients, but in none of the placebo-treated patients. 

Clinical effects In HF patients, digoxin has been proven to reduce symptoms, improve NYHA class, increase exercise time, modestly increase LVEE enhance cardiac output, and decrease HF hospitalizations (56,57). The Randomized Assessment of Digoxin on Inhibitors of the Angiotensin-Converting Enzyme (RADIANCE) (58) and Prospective Randomized study Of Ventricular Failure and the Efficacy of Digoxin (PROVED) (59) trials demonstrated that these beneficial effects are lost when digoxin is withdrawn from the medical therapy. Digoxin withdrawal has been associated... 

Metolazone occupies an intermediate position between the thiazide diuretics and the more potent loop diuretics (1). It is more effective than the thiazides in moderate to advanced renal insufficiency (SED-8, 488) (SED-9, 355). In patients with normal renal function its antihypertensive effect compares favorably with that of bendroflumethia-zide. When severe heart failure is refractory to conventional triple therapy (high-dose loop diuretic, digoxin, and angiotensin-converting enzyme inhibitor) metolazone can restore diuresis, with weight loss and clinical improvement. 

McMahon FG, Weinstein SP, Rowe E, Ernst KR, Johnson F, Fujioka K. Sibutramine in Hypertensives Clinical Study Group. Sibutramine is safe and effective for weight loss in obese patients whose hypertension is well controlled with angiotensin-converting enzyme inhibitors. J Hum Hypertens 2002 16(1) 5-11. 

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