Thiazide diuretics with indomethacin

Erectile dysfunction (ED), the inability to achieve or maintain a penile erection sufficient to permit satisfactory sexual intercourse, is estimated to affect over 100 million men worldwide, with a prevalence of 39% in those of 40 years. Its numerous causes include cardiovascular disease, diabetes mellitus and other endocrine disorders, alcohol and substance abuse, and psychological factors (14%). While the evidence is not conclusive, drug therapy is thought to underlie 25% of cases, notably from antidepressants (SSRI and tricyclic), phenothiazines, cypro-terone acetate, fibrates, levodopa, histamine H -receptor blockers, phenytoin, carbamazepine, allopurinol, indomethacin, and possibly adrenoceptor blockers and thiazide diuretics. 

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). 

A See Table 4.3D. Antihypertensive effects T by diuretics or p-blockers. Antihypertensive effects i by indomethacin. Serum K+ t with K+-sparing diuretics. Usually used in conjunction with a thiazide diuretic. 

Lithium intoxication can be precipitated by the use of diuretics, particularly thiazides and metola-zone, and ACE inhibitors. NSAIDs can also precipitate lithium toxicity, mainly due to NSAID inhibition of prostaglandin-dependent renal excretion mechanisms. NSAIDs also impair renal function and cause sodium and water retention, effects which can predispose to interactions. Many case reports describe the antagonistic effects of NSAIDs on diuretics and antihypertensive drugs. The combination of triamterene and indomethacin appears particularly hazardous as it may result in acute renal failure. NSAIDs may also interfere with the beneficial effects of diuretics and ACE inhibitors in heart failure. It is not unusual to see patients whose heart failure has deteriorated in spite of increased doses of frusemide who are also concurrently taking an NSAID. 

Many interactions with lithium have been described. Thiazide and loop diuretics decrease lithium excretion predisposing to serious lithium toxicity. Also non-steroidal anti-inflammatory agents, especially indomethacin can increase the risks for lithium toxicity due to decreased renal excretion. 

---