Hydrochlorothiazide amiloride with

Sulindac does not appear to reduce either the hypotensive or diuretic effects of hydrochlorothiazide, and may even slightly enhance the antihypertensive effects. Another study found that sulindac did not alter the antihypertensive eflicacy of hydrochlorothiazide/amiloride given with beta blockers. Similarly, sulindac 200 mg twice daily for one month did not alter the antihypertensive effect of the combinations of hydrochlorothiazide 25 mg daily with fosinopril 10 to 40 mg daily, or lisinopril 10 to 40 mg daily. ... 

Isolated cases of nephrotoxicity have been described when patients taking ciclosporin were given either amiloride with hydrochlorothiazide, metolazone, or mannitol. Furosemide can possibly protect the kidney against ciclosporin damage. The concurrent use of ciclosporin with thiazides, but not loop diuretics, may increase serum magnesium levels. The concurrent use of ciclosporin with potassium-sparing diuretics may cause hyperkalaemia. 

In nephrogenic diabetes insipidus the kidney s ability to respond to AVP is impaired by different causes, such as drugs (e.g. lithium), chronic disorders (e.g. sickle cell disease, kidney failure) or inherited genetic disorders (X-linked or autosomal NDI). This type of diabetes insipidus can not be treated by exogenous administration of AVP or AVP analogues. Instead, diuretics (hydrochlorothiazide combined or not with amiloride) and NSAI (indomethacin) are administrated to ameliorate polyuria. 

Amiloride (Midamor) is used in the treatment of CHF and hypertension and is often used with a thiazide diuretic. Spironolactone and triamterene are also used in tiie treatment of hypertension and edema caused by CHF, cirrhosis, and the nephrotic syndrome Amiloride, spironolactone, and triamterene are also available with hydrochlorothiazide, a thiazide diuretic that enhances tiie antihypertensive and diuretic effects of the drug combination while still conserving potassium. 

These K+-sparing diuretics have low efficacy when used alone, since only a small amount of total Na+ reabsorption occurs at more distal sites of the nephron. These compounds are used primarily in combination with other diuretics, such as the thiazides and loop diuretics, to prevent or correct hypokalemia. The availability of feed-dose mixtures of thiazides with nonsteroidal K+-sparing compounds has proved a rational form of drug therapy. Both triamterene and amiloride are available alone or in combination with hydrochlorothiazide. 

Amiloride exerts an inhibitory action on sodium channels under the influence of aldosterone in the distal tubule. Its action is therefore complementary to that of the thiazides and, used with them, it augments sodium loss and but limits potassium loss. One such combination, co-amilozide, (Moduretic) (amiloride 2.5-5 mg plus hydrochlorothiazide 25-50 mg), is used for hypertension or oedema. The maximum effect of amiloride occurs about 6 h after an oral dose with a duration of action >24h 21 h). The oral dose is 5-20 mg daily. 

Patients with congenital nephrogenic diabetes insipidus are often treated with a combination of a thiazide and a potassium-sparing diuretic, without consensus on the preferred potassium-sparing diuretic. A Japanese adult was systematically studied to determine the renal effects of hydrochlorothiazide plus amiloride and hydrochlorothiazide plus triamterene (1). The combination with amiloride was superior to that with triamterene in preventing excessive urinary potassium loss, hjrpokalemia, and metabolic alkalosis. These results suggest that amiloride is the preferred add-on therapy to hydrochlorothiazide in nephrogenic diabetes insipidus. 

Co-administration of potassium-sparing diuretics with ACE inhibitors can cause severe hyperkalemia (SED-14, 674). In a retrospective study, five patients developed extreme hyperkalemia (9.4-11 mmol/1) within 8-18 days of starting combination therapy with co-amilozide (amiloride -I- hydrochlorothiazide) and an ACE inhibitor (5). 

Konoshita T, Kuroda M, Kawane T, Koni I, Miyamori I, Tofuku Y, Mabuchi H, Takeda R. Treatment of congenital nephrogenic diabetes insipidus with hydrochlorothiazide and amiloride in an adult patient. Horm Res... 

The use of fixed combination of a thiazide and a potassium-sparing drug, often Moduretic (hydrochlorothiazide 50 mg with amiloride 5 mg), has been consistently implicated in diuretic-induced hyponatremia. Treatment with chlorpropamide (200-800 mg/day) along with Moduretic has precipitated hyponatremia in several cases (96). Simultaneous use of Moduretic with trimethoprim has also been reported to increase the risk (97). The mechanism appears to be impairment of the clearance of free water, resulting in dilutional hyponatremia. Whether... 

Zalin AM, Hutchinson CE, Jong M, Matthews K. Hyponatraemia dnring treatment with chlorpropamide and Modnretic (amiloride pins hydrochlorothiazide). BMJ (Clin Res Ed) 1984 289(6446) 659. 

Indometacin reduces the effect of diuretics (69). Combination of indometacin with Moduretic (co-amilo-zide amiloride + hydrochlorothiazide) results in hyperkalemia (70). 

Amiloride is available as a 5-mg tablet. The usual starting dose is 5 mg daily however, 10 mg can be given in those with severe hypokalemia. This is also available as a combination product with hydrochlorothiazide 50 mg. The most common side effects are hyperkalemia and metabohc acidosis. ... 

Hyperkalemia should not be treated with drugs that interfere with aldosterone production (eg, losartan, an angiotensin II receptor blocker) or collecting tubule potassium excretion (eg, amiloride, spironolactone, triamterene). These agents are all capable of increasing serum potassium. Hydrochlorothiazide would not reduce serum potassium rapidly, but it would not increase it. The answer is (B). 

A hospital report describes 8 cases of low serum sodium concentrations observed over a 5-year period in patients taking chlorpropamide and Mo-duretic (hydrochlorothiazide 50 mg with amiloride 5 mg). ... 

Excessively low sodium levels have been seen in a few patients taking hydrochlorothiazide with amiloride or triamterene when they were given trimethoprim or co-trimoxazole. Trimethoprim may cause hyperkalaemia and this may be additive with potassium-sparing diuretics, including the aldosterone antagonists. 

A 75-year-old woman with multiple medical conditions taking methyl-dopa, levothyroxine and co-amilozide (hydrochlorothiazide with amiloride) developed nausea and anorexia, and was found to have hyponatraemia (plasma sodium 107 mmol/L), within 4 days of starting to take trimethoprim 200 mg twice daily. The problem resolved when the diuretics and trimethoprim were stopped. When re-challenged 4 months later with trimethoprim, hyponatraemia did not occur, but it developed rapidly when co-amilozide was also restarted. The authors of this report say that they have seen several other patients who developed hyponatraemia within 4 to 12 days of starting trimethoprim or co-trimoxazole, all of whom were elderly and all but one of whom were taking a diuretic [unnamed]. ... 

Alon U, Costanzo LS, Chan JCM Additive hypocalciuric effects of amiloride and hydrochlorothiazide in patients treated with calcitiiol. Miner Electrofyte Metab (1984) 10, 219-Z6. 

Retrospective analysis of clinical study data found no evidence that the safety or efficacy of lovastatin was altered by the use of potassium-sparing diuretics (hydrochlorothiazide with triamterene or amiloride), or thiazide diuretics (mostly hydrochlorothiazide). Another retrospective study of 19 patients found that the addition of lovastatin to diuretic treat-... 

In addition to these studies at least 6 cases of lithium toxicity have been seen when hydrochlorothiazide was given to patients taking lithium. Hydrochlorothiazide was either given with amiloride, " spironolactone or triamterene. See also Lithium + Diuretics Potassium-sparing , p.ll22. 

Figure8.19 Predicted(a)andexperimental(b)chromatogramsofamixtureof compounds eluted with a 0.15 M SDS-7% 1-propanol mobile phase, buffered at pH 3.0. Compounds hydrochlorothiazide (HT), chlorthalidone (CL), bendroflumethiazide (BE), atenolol (AT), amiloride (AM), hydralazine (HY), metoprolol (ME), and oxprenolol (OX). Reprinted from Ref. 14 with permission of the Royal Society of Chemistry.

Figure 10.6 Contour map of global resolution for the separation of a mixture of three P-blockers (atenolol, metoprolol and oxprenolol), four diuretics (amiloride, bendroflumethiazide, chlorthalidone and hydrochlorothiazide), and hydralazine, eluted with mobile phases of SDS and propanol at pH 3. Reprinted from Ref 13 with permission of the Royal Chemical Society,...

A procedure for the determination of diuretics of different therapeutical character high (bumetanide, ethacrynic acid, furosemide), intermediate (bendroflumethiazide, chlorthalidone, hydrochlorothiazide, xipamide) and low (acetazolamide, amiloride, spironolactone, triamterene) efficacy diuretics, and the uricosuric agent probenecid, in urine samples, illustrates a method development implying the control of pH, surfactant and modifier [23]. The greatest analytical problems in the detection of these compounds are basically their wide variety of chemical structures, functional groups and protonation constants. This implies the use of several experimental conditions for their analysis with conventional aqueous-organic mobile phases and laborious liquid-liquid or solid-liquid extraction prior to chromatographic separation. In contrast, the same micellar eluent can produce a satisfactory separation after direct injection. 

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