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Effects of enalapril with and without hydrochlorothiazide in hypertensive patients with non-insulin-dependent diabetes mellitus.

Bilo HJ, Westerman RF, Nicolaas-Merkus AM, Donker AJ.

Department of Medicine, University Hospital, Free University, Amsterdam, The Netherlands.

The purpose of this study was to evaluate the effects of the ACE inhibitor enalapril (E) on blood pressure and metabolic control in 15 hypertensive patients with non-insulin-dependent diabetes mellitus. When the treatment goal was not reached with enalapril alone, hydrochlorothiazide (HCTZ) was added. A diastolic blood pressure (DBP) below 90 mmHg was achieved in seven patients with enalapril alone (47%), and in an additional four (27%) with concomitant hydrochlorothiazide. No significant adverse effects of enalapril occurred and all patients completed the study. Monotherapy with enalapril did not affect metabolic control or renal function. Addition of HCTZ to E did not consistently result in further lowering of blood pressure and caused deterioration of both the degree of metabolic control and renal function. We, therefore, conclude that monotherapy with enalapril can be a safe and satisfactory treatment for hypertensive patients with NIDDM. Caution is needed, however, when HCTZ is added, since this may adversely affect metabolic control and renal function whereas the effect on blood pressure may be variable.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2853659&dopt=Abstract hydrochlorothiazide Microzide



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The dissolution rate and bioavailability of hydrochlorothiazide in pellet formulations.

Herman J, Remon JP, Lefebvre R, Bogaert M, Klinger GH, Schwartz JB.

Laboratory of Pharmaceutical Technology, State University of Gent, Belgium.

The influence of non-active ingredients in the manufacture of pellets on in-vitro dissolution rate and on bioavailability of hydrochlorothiazide has been studied. Pellets were formulated using either microcrystalline cellulose or microcrystalline cellulose-carboxymethylcellulose sodium blends as matrix, and hydrochlorothiazide as the active ingredient. In-vitro drug release from the different pellet formulations was retarded in comparison to a conventional tablet formulation and was dependent on the nature of the non-active ingredient and, for the microcrystalline cellulose-carboxymethylcellulose sodium blend, of the dissolution medium. In-vivo bioavailability of both pellet formulations was low compared with that of the conventional tablet and the plasma concentration-time profiles did not suggest slow release.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2899142&dopt=Abstract hydrochlorothiazide Microzide



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The effect of hydrochlorothiazide on the composition of renal papillary interstitial fluid in the rat.

Shirley DG, Skinner J, Walter SJ.

Department of Physiology, Charing Cross & Westminster Medical School, London, UK.

The effect of chronic hydrochlorothiazide administration on the composition of renal papillary interstitial fluid was investigated in the rat. Hydrochlorothiazide alone had no effect on papillary composition. However, when the sodium depletion that usually accompanies thiazide treatment was minimized by allowing the rats access to hypertonic NaCl solution, hydrochlorothiazide administration resulted in significant reductions in papillary osmolality, and sodium and potassium concentrations. It is suggested that the effects of hydrochlorothiazide on the renal papilla might be mediated by thiazide-induced hypokalaemia, and that under normal circumstances these effects are masked by the concomitant sodium depletion.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2900312&dopt=Abstract hydrochlorothiazide Microzide



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Renal responses to atrial natriuretic factor in hydrated and hydropenic dogs.

Seymour AA, Smith SG, Mazack EK.

Department of Pharmacology, Merck, Sharp and Dohme Research Laboratories, West Point, PA.

Atrial natriuretic factor (ANF 101-126) was compared to the standard diuretics, furosemide and hydrochlorothiazide, and to the vasodilator, acetylcholine in hydrated and dehydrated anesthetized dogs. ANF 101-126 (20 pmole/kg/min, ira) modestly reduced solute-free water clearance in water-loaded dogs and slightly lowered free water reabsorption in dehydrated animals. This pattern of responses most closely resembled those produce by 10 mg/kg, ira of the distally-acting diuretic, hydrochlorothiazide and a natriuretic dose of acetylcholine (2.5 micrograms/kg/min, ira). In contrast, the loop diuretic, furosemide (1 mg/kg, ira) drastically suppressed both free water clearance and reabsorption. ANF 101-126 produced changes in free water handling which were not readily distinguishable from those induced by either hydrochlorothiazide, a distally-acting diuretic, or acetylcholine, a vasodilator.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2970568&dopt=Abstract hydrochlorothiazide Microzide



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Interaction of amiloride and hydrochlorothiazide with atrial natriuretic factor in the medullary collecting duct.

Wilson DR, Honrath U, Sonnenberg H.

Department of Physiology, University of Toronto, Ont., Canada.

Medullary collecting duct function was studied using the in vivo microcatheterization technique in three groups of rats receiving amiloride, hydrochlorothiazide, or both diuretics. In each group of animals, atrial natriuretic factor (ANF99-126) was given in the second phase of the experiment. The combination of amiloride and hydrochlorothiazide resulted in a more marked natriuresis than either diuretic given as a single agent. Sodium reabsorption in the medullary collecting duct, as a fraction of the delivered load, was reduced from 64% (amiloride) and 69% (hydrochlorothiazide) to 29% (amiloride and hydrochlorothiazide). Atrial natriuretic factor reduced collecting duct sodium reabsorption when added to amiloride or hydrochlorothiazide to 23% and to 41%, respectively, but had no additional effect when given with amiloride and hydrochlorothiazide. Potassium excretion with amiloride and hydrochlorothiazide was intermediate between amiloride or hydrochlorothiazide given as single agents. With the diuretic combination, potassium transport showed no significant reabsorption or secretion along the medullary collecting duct, amiloride was associated with potassium reabsorption, and hydrochlorothiazide was associated with potassium secretion in the duct. The results confirm the importance of the medullary collecting duct as a site of diuretic action. The known additive effects of amiloride and hydrochlorothiazide on sodium excretion and the opposing effects of these agents on potassium excretion occur, to a major degree, in the medullary collecting duct. Furthermore, the additive effects of amiloride and ANF indicate that blocking of amiloride-sensitive sodium channels is not the only mechanism of action of ANF on duct salt transport in vivo.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2970886&dopt=Abstract hydrochlorothiazide Microzide