Combination Of Thiazide Research Articles

Pharmacotyping of hypokalaemic salt-losing tubular disorders.

Long standing confusion exists in the terminology of hypokalaemic salt-losing tubulopathies (SLTs). SLTs are autosomal recessively transmitted and characterized by normotensive secondary hyperreninism/hyperaldosteronism with hypokalaemic metabolic alkalosis. Historically, four phenotypical variants have been described: (1) the (classic) Bartter syndrome (cBS), (2) the hypomagnesaemic hypocalciuric Gitelman syndrome (GS), (3) the hypercalciuric hyperprostaglandin-E-syndrome (HPS) or antenatal Bartter syndrome (aBS) and (4) the hyperprostaglandin-E-syndrome with sensorineural deafness (HPS + SND). The latter two syndromes are the most severe variants with antenatal manifestation with polyhydramnios and life-threatening course of salt- and water-loss. Defects in five renal membrane proteins involved in electrolyte reabsorption have been identified: In HPS-patients mutations in (1) either the furosemide-sensitive sodium-potassium-chloride cotransporter NKCC2, or (2) in the potassium channel ROMK have been identified, and (3) HPS + SND is caused by mutations in the beta-subunit of the chloride channels ClC-Kb and -Ka (named barttin), all mimicking the major pharmacological effects of furosemide with minor potassium-wasting in ROMK-patients as seen in patients treated with simultaneous furosemide and amiloride, and minor calcium-wasting in Barttin-patients resembling the combination of furosemide and thiazides. (4) cBS is caused by mutations in the chloride channel ClC-Kb with similar clinical characteristics as seen under combination of thiazides and furosemide, (5) GS is caused by mutations in the thiazide-sensitive sodium-chloride cotransporter NCCT resembling the effect of long-term thiazide administration. The combination of pharmacology and genetics suggests a new terminology for the above described SLTs: Furosemide-like-SLT for HPS caused by NKCC2-mutations, furosemide/amiloride-like-SLT for HPS caused by ROMK-mutations, furosemide/thiazide-like-SLT for HPS + SND, thiazide/furosemide-like-SLT for cBS, and thiazide-like-SLT for GS.

WHEN AND HOW TO EVALUATE A PATIENT WITH NEPHROLITHIASIS

Nephrolithiasis is a common disorder that afflicts up to 12% of the population and continues to be a significant cause of patient injury. Evaluation of these patients should include the assessment of their comorbidities and underlying medical conditions. Patients who form stones can undergo a streamlined evaluation. A cause can be found in more than 90% of these patients. With medical treatment, stone-recurrence rates can be decreased by 85% for calcium oxalate stone formation, which affects a large proportion of patients. Introduction of nonspecific medical therapy in uncomplicated calcium stone disease may improve the quality of life for these patients and allow utilization a simple diagnostic protocol. This is in contrast to the previous recommendations of disease-specific therapy. Because patients without complications represent the majority of those who form stones, a simplified approach greatly reduces the cost of evaluation and treatment. Underlying medical conditions, however, require disease-specific therapy. The protocol represented here should aid physicians and patients in the approach to management of stone disease. The fasting calcium-load test is not required, and the entire evaluation can be performed in an ambulatory setting in two visits. Two 24-hour urine samples should be obtained on a random and restricted diet. Patients who form calcium stones can be subdivided into those who form hypercalciuric and normocalciuric stones. Patients who form normocalciuric stones are treated with conservative measures (increased fluid intake) and potassium and magnesium citrate. Patients who form hypercalciuric stones are treated with a combination of thiazides and potassium and magnesium citrate.

Unprocessed Bran and Intermittent Thiazide Therapy in Prevention of Recurrent Urinary Calcium Stones

Both urinary calcium excretion and renal stone episodes are increased during the summer in Finland. Since thiazide and unprocessed bran are known to decrease urinary calcium excretion, we treated 73 patients with recurrent urinary stone formation by giving them unprocessed bran and intermittent thiazide. Of the patients, 32 had absorptive hypercalciuria and 41 had normal urinary calcium values. All patients were on a low-calcium and low-oxalate diet and took 40 g bran daily. Fourteen of the hypercalciuric and 14 of the normocalciuric patients were randomly allocated to use hydrochlorothiazide 50 mg b.i.d. from May to September. Reduction of stone formation was seen in all groups. The combination of thiazide + bran was superior to the bran on its own in inhibition of stone formation. Only 3/11 (27%) stones passed through during the summer in the thiazide + bran group as compared with the 11/17 (65%) in the bran group.

Thiazides and loop-diuretics therapeutic aspects.

Thiazides and compounds with similar models of action exert their most important renal effects on the cortical-diluting segment of the nephron, most likely from the peritubular side. In contrast, the most important site of action of loop-diuretics is the luminal side of the ascending part of the diluting segment. The different sites of action explain the clinically proven efficacious combination of thiazides and loop-diuretics in severe cardiac failure. Most thiazides and loop-diuretics are eliminated via renal tubular secretion, which leads to decreased renal clearance in patients with chronic heart failure (CHF) as their renal blood flow is decreased even if glomerular filtration rate (GFR) is maintained. A rational approach to enhance the effects of loop-diuretics is to combine them with drugs that increase renal blood flow, thereby increasing the rate of delivery of the drug to its site of action. Dilutional hyponatremia is an important complication of treatment with diuretics. An efficacious treatment of that condition seems to be a combination of loop-diuretics and ACE-inhibitors. Thiazides decrease the urinary excretion of calcium, while loop-diuretics have the opposite effect. The possibility of loop-diuretic induced osteopenia cannot be ruled out, which should be considered when choosing between thiazides and loop-diuretics for the treatment of mild to moderate CHF.

Use of labetalol in moderate to severe hypertension.

An open study was undertaken in 31 patients with moderate to severe hypertension to compare labetalol (a competitive antagonist of both alpha-adrenoreceptors and beta-adrenoreceptors) alone and in combination with a thiazide diuretic, with a combination of thiazide, beta-adrenergic blocking agent and the alpha-adrenoreceptor blocker prazosin. After introduction of labetalol, six patients withdrew because of intolerable side effects. All 25 remaining patients were controlled on diuretic and labetalol. On labetalol alone, 14 patients were controlled, two withdrew because of side effects and nine had inadequate blood pressure control. Labetalol is an effective antihypertensive agent, but side effects are common and it has few advantages over drugs presently available.

Controlled Clinical Study on Antihypertensive Treatment with a Diuretic and Methyldopa Compared with a β‐Blocking Agent and Hydralazine

Twenty-eight previously untreated patients with essential hypertension were included in a randomized double-blind cross-over study comparing the results of treatment with the established combination of a thiazide and methyldopa (regimen A) with the combination of a beta-receptor blocker and hydralazine (regimen B). Three patients each developed intolerable side-effects on each regimen but they were all treated successfully on the alternative regimen. The remaining 22 patients obtained a significant reduction in BP at rest and during exercise on both treatments, with no significant difference between the two schedules. Heart rate was significantly reduced at rest and during exercise with regimen B, while a significant reduction was also obtained following exercise on regimen A. There was no significant difference between the two regimens as to tolerable side-effects during treatment, which were registered in about 60% of the patients on each scheme. However, 64% of the patients were treated satisfactorily without side-effects on either regimen. It is concluded that the combination of a beta-blocking agent and hydralazine is without obvious advantages compared with the combination of thiazide and methyldopa in obtaining initial BP control in patients with essential hypertension.

Hydrostatic pressures in peritubular capillaries and tubules in the rat kidney

Hydrostatic pressures in peritubular capillaries and tubules in the rat kidney

Medical management of ascites in cirrhosis of the liver. I. Diuretic drugs.

Diuretics were given alone or in combination to normal subjects and cirrhotic patients with ascites. Patients unable to excrete sodium and water under basal conditions (Stage I), were found to be systematically resistant to all drugs tested. Patients with ascites and essentially normal sodium and water excretion made good diuretic responses to all drugs. Resistance of patients was overcome by the combination of thiazides and meralluride. Potassium output increased in all cases, even in the absence of satisfactory diuretic responses. Potassium supplements should therefore be given. Maintenance of relatively low water intake was of value in preventing hyponatremia. Strict low sodium intake was found essential for good over‐all results.