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Direct tubular effect on calcium retention by hydrochlorothiazide.

Krause U, Zielke A, Schmidt-Gayk H, Ehrenthal W, Beyer J.

Department of Internal Medicine, University Clinic, Mainz, FRG.

Previous studies with hydrochlorothiazide revealed a calcium retaining effect of this substance. The mechanism by what this is done is still matter of controverse discussion. Effects of hydrochlorothiazide on vitamin D metabolism have been reported as well as those on parathyroid function. To further clarify the calcium retaining potency of hydrochlorothiazide (HCTZ) we treated 10 healthy young volunteers for four weeks with 2 x 50 mg HCTZ. In all volunteers we observed a marked decrease in urinary calcium excretion as well as in calcium clearance. Furthermore, we found a slight rise in ionized serum calcium (6.7%) and in intact PTH, as well as a 36% drop in 1,25-(OH)2-D3-levels. These effects were reversible after discontinuation of the treatment. No change was observed in urinary cAMP, phosphate excretion, serum anorganic phosphate levels, serum calcitonin and magnesium levels. Data presented here suggest that treatment with HCTZ causes a persistent reduction in calcium excretion through direct tubular effects, inhibits hydroxylation of vitamin D, and does not affect parathyroid function.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2592738&dopt=Abstract hydrochlorothiazide Microzide



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Effect of temperature and fat content on the solubility of hydrochlorothiazide and chlorothiazide in milk.

Macheras PE, Koupparis MA, Antimisiaris SG.

Department of Pharmacy, University of Athens, Greece.

The solubility of hydrochlorothiazide and chlorothiazide in milk has been studied. Experiments were carried out at 5, 15, 25, and 37 degrees C on a buffer solution of pH 6.5, a 2.6% solution of casein, bovine skim milk samples, and bovine milk samples with fat contents of 0.75, 1.70, and 3.50%. The "total" solubility of both drugs in the media studied was higher than the buffer solubility. The highest "total" solubility for both drugs was observed in skim milk. Based on binding data of thiazides to milk, the "total" solubility was split into "free" and "bound" solubility. The increases of solubility noted cannot be explained on the basis of drug-milk binding data. The enhancement of solubility was attributed to the increase of intrinsic solubility of drugs in milk. Results of the thermodynamic analysis of solubility data showed that a different solubilization process of hydrochlorothiazide may be responsible for the high solubility values found in skim milk for this drug. In contrast, the thermodynamic parameters of chlorothiazide in all types of milk are similar, indicating a common solubilization mechanism. The biopharmaceutical significance of the findings is discussed in light of the freeze-dried drug-milk formulations and coadministration of drugs with milk in general.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2621578&dopt=Abstract hydrochlorothiazide Microzide



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[Hypotensive and metabolic effects of small doses of hydrochlorothiazide in the long-term treatment of elderly patients with systolic arterial hypertension]

[Article in Polish]

Halawa B.

In a group of elderly patients with systolic hypertension the hypotensive efficacy and adverse effects were studied of hydrochlorothiazide given in daily doses of 25 mg in a year. A fall of systolic and diastolic arterial blood pressure was obtained in 86% of these patients. Adverse effects included reduced concentration of potassium and magnesium ions in the serum and lymphocytes, but this reduction was small and appeared mainly in the serum. The used doses of hydrochlorothiazide had no effect on plasma renin activity, and on the serum levels of aldosterone, glucose, uric acid, cholesterol and triglycerides.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2623867&dopt=Abstract hydrochlorothiazide Microzide



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[Effect of long-term treatment with propranolol or hydrochlorothiazide on biochemical risk factors of coronary disease in patients with hypertension]

[Article in Polish]

Witkowska M, Lukasik S, Kawecka M, Moszczynska J, Karolko B.

In 59 patients with mild or moderate essential hypertension effects of propranolol and hydrochlorothiazide on serum lipids, fibrynogen, glucose and uric acid concentrations as well as serum euglobulins fibrynolysis time were studied. 36 patients received propranolol and 23 subjects hydrochlorothiazide. Follow-up time was 1 year. Statistically significant increases of serum triglycerides, fibrynogen, levels and total cholesterol/HDL cholesterol LDH/HDL indices in comparison with their initial values were stated in a propranolol group. Significant serum cholesterol increase after 6 month therapy was the most substantial metabolic change in a hydrochlorothiazide group. Alterations of lipids indices in both groups were especially intensive in patients with pretreatment stated disturbances of lipids metabolism.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2634150&dopt=Abstract hydrochlorothiazide Microzide



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Hydrochlorothiazide is not additive to verapamil in treating essential hypertension.

Nicholson JP, Resnick LM, Laragh JH.

Cardiovascular Center, New York Hospital-Cornell Medical Center, New York 10021.

Calcium channel blockers, a newer class of antihypertensive medications, have gained considerable acceptance as monotherapeutic agents, particularly in low renin hypertension where diuretics are also most effective. To study whether thiazide diuretics exert an additional antihypertensive effect in the setting of calcium channel blockade, we gave verapamil hydrochloride (360 mg/d) or hydrochlorothiazide (25 mg/d) alone and in combination in an open study to 13 hypertensive patients with mild to moderate essential hypertension. Both verapamil and hydrochlorothiazide lowered blood pressure (170 +/- 17/109 +/- 6 mm Hg pretreatment to 150 +/- 25/95 +/- 8 mm Hg with verapamil; 170 +/- 5/109 +/- 2 mm Hg pretreatment to 164 +/- 25/103 +/- 10 mm Hg with hydrochlorothiazide), but addition of hydrochlorothiazide to verapamil resulted in no added benefit (150 +/- 25/95 +/- 8 mm Hg vs 150 +/- 20/95 +/- 6 mm Hg). Furthermore, while hydrochlorothiazide lowered serum potassium values (4.2 +/- 0.25 mmol/L to 3.7 +/- 0.35 mmol/L) and stimulated plasma renin activity (1.5 +/- 1.3 ng/mL/h) pretreatment to 3.3 +/- 2.7 ng/mL/h with verapamil), verapamil only modestly elevated renin activity (1.5 +/- 1.3 ng/mL/h pretreatment to 2.7 +/- 2.5 ng/mL/h with verapamil) and did not lower potassium values. Altogether, the data suggest that in essential hypertension, at least for verapamil, concurrent diuretic therapy may not be helpful or warranted.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2643413&dopt=Abstract hydrochlorothiazide Microzide