Angiotensin-converting enzyme inhibitors drug interactions with

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. 

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... 

Renal function should be closely monitored when patients on lithium treatment are given angiotensin converting enzyme inhibitors. Doses of both drugs should be chosen with caution to avoid serious drug interaction [27]. 

Most of the renal tubular reabsorption ofU occurs in the proximal tubule. Nevertheless, Id retention can be increased by any diuretic that leads to depletion of Na, particularly the thiazides (see Chapter 28). Renal excretion can be increased by administration of osmotic diuretics, aceta-zolamide or aminophylline, and triamterene. Spironolactone does not increase the excretion of LiL Some nonsteroidal anti-inflammatory agents can facilitate renal proximal tubular resorption of Id and thereby increase concentrations in plasma to toxic levels. This interaction appears to be particularly prominent with indomethacin, but also may occur with ibuprofen, naproxen, and COX-2 inhibitors, and possibly less so with sulindac and aspirin. A potential drug interaction can occur with angiotensin-converting enzyme inhibitors, causing lithium retention (see Chapter 29). 

Drug Interactions Xanthine oxidase, a key enzyme in the catabolism of azathioprine metabolites, is blocked by aUopurinol. If azathioprine and allopurinol are used concurrently, the azathioprine dose must be decreased to 25-33% of the usual dose it is best not to use these two drugs together. Adverse effects resulting from coadministration of azathioprine with other myelosuppres-sive agents or angiotensin-converting enzyme inhibitors include leukopenia, thrombocytopenia, and anemia as a result of myelosuppression. 

Celecoxib is currently indicated for the relief of signs and symptoms of osteoarthritis and rheumatoid arthritis and to reduce the number of adenomatous colorectal polyps in familial adenomatous polyposis as an adjunct to usual care. Celecoxib is at least as effective as naproxen in the symptomatic management of osteoarthritis and at least as effective as naproxen and diclofenac in the symptomatic treatment of rheumatoid arthritis, and it is less likely to cause adverse Gl effects. Celecoxib appears to be effective in the management of pain associated with both of these arthritic conditions, but effectiveness in acute or chronic pain has not been fully demonstrated. Unlike aspirin, celecoxib does not exhibit antiplatelet activity. Concomitant administration of aspirin and celecoxib may increase the incidence of Gl side effects. Another notable potential drug interaction with celecoxib is its ability, like other NSAIDs, to reduce the blood pressure response to angiotensin-converting enzyme inhibitors. A more detailed discussion of the chemical, pharmacological, pharmacokinetic, and clinical aspects of celecoxib is available (81). 

Intestinal absorption of beta-lactams occurs at least in part by an active mechanism involving a dipeptide carrier, and this pathway can result in interactions with dipeptides and tripeptides (196,197), which reduce the rate of absorption of the beta-lactams. In particular, angiotensin-converting enzyme (ACE) inhibitors, which have an oligopeptide structure, are absorbed by the same carrier (198) and interact with beta-lactams in isolated rat intestine (199). However, there might be a second site of interaction between ACE inhibitors and beta-lactams. Both groups of substances are excreted by the renal anionic transport system, and concomitant administration of both drugs sometimes results in pronounced inhibition of the elimination of beta-lactams (200). In the case of cefalexin, it may not lead to toxic effects. However, when more toxic beta-lactams are used, the possibility of this interaction has to be kept in mind. 

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