Angiotensin-converting enzyme interactions

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... 

Figure 3.4 Interactions of (A) substrate, (B) captopril, and (C) enalaprilate with the active site of angiotensin converting enzyme.

The most potentially serious drug interactions include the concomitant use of NSAIDs with lithium, warfarin, oral hypoglycemics, high-dose methotrexate, antihypertensives, angiotensin-converting enzyme inhibitors, fi-blockers, and diuretics. 

Meune, C., et al. (2000). Interaction between angiotensin-converting enzyme inhibitors and aspirin, a review, Eur. J. Clin. Pharmacol., 56, 609-620. 

Isbir, T., Agachan, B., YUmaz, H., Aydin, M., Kara, I., Eker, D., Eker, E. (2001) Interaction between apohpoprotein-E and angiotensin-converting enzyme genotype in Alzheimer disease. Am. J. Alzheim. Dis. Other Dem., 16,205-210. 

Diclofenac is a non-steroidal anti-inflammatory drug. NSAIDs interact with both angiotensin-converting enzyme inhibitors, such as enalapril, and beta-adrenoceptor blockers, such as atenolol, resulting in antagonism to the hypotensive reaction, leading to a hypertensive reaction. NSAIDs interact with... 

There is an increased risk of hyperkalaemia when ciclosporin is given with Coversyl, which contains perindopril, an angiotensin-converting enzyme inhibitor. Risk of nephrotoxicity associated with ciclosporin is increased with concomitant use with quinolones. Ciproxin contains ciprofloxacin, which is a quinolone. Tenormin contains atenolol, which is a beta-adrenoceptor blocker and there are no interactions between these agents and ciclosporin. 

Nakagawa, K., Ueno, A., and Nishikawa, Y. (2006). Interactions between carnosine and captopril on free radical scavenging activity and angiotensin-converting enzyme activity in vitro. Yakugaku Zasshi 125, 37-42. 

McNamara, D.M., R. Hoiubkov, K. Janosko, A. Palmer, J.J. Wang, G.A. MacGowan, S. Muraii, W.D. Rosenbium, B. London, and A.M. Eeidman, Pharmacogenetic interactions between beta-blocker therapy and the angiotensin-converting enzyme deletion... 

Drug Interactions Allopurinol Agents affecting myelopoiesis Angiotensin converting enzyme inhibitors... 

---