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Effects of a non-absorbable osmotic load on drug absorption in healthy volunteers.

Riley SA, Kim M, Sutcliffe F, Kapas M, Rowland M, Turnberg LA.

Department of Medicine, Hope Hospital, Manchester.

1. We have studied the effects of a non-absorbable osmotic load on the absorption of a multicomponent solution of frusemide, atenolol, hydrochlorothiazide and salicylic acid in six healthy volunteers. 2. Each subject was studied on up to four separate occasions. The drugs were administered in one of four solutions: a) a mannitol/electrolyte solution, b) a double-strength mannitol/electrolyte solution, c) a glucose/electrolyte solution and d) water. Lactulose or sulphasalazine were added as oro-caecal transit markers. Lactulose was included in the mannitol- and glucose-based solutions, adding a further non-absorbable osmotic load, and sulphasalazine was added to the water, adding little osmotic load. 3. The absorption of atenolol and hydrochlorothiazide was two- to three-times less from all lactulose-containing solutions than from the sulphasalazine-containing solution. The absorption of frusemide and salicylic acid was similar from all four solutions. 4. The largest non-absorbable osmotic load impaired the absorption of atenolol and hydrochlorothiazide most and the incorporation of glucose only partly restored absorption. 5. These results suggest that transmucosal water movement is an important determinant of atenolol and hydrochlorothiazide absorption but is less relevant for the absorption of frusemide and salicylic acid. Furthermore, these data demonstrate a previously unrecognised interaction between a commonly prescribed laxative--lactulose, and atenolol and hydrochlorothiazide.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1633066&dopt=Abstract hydrochlorothiazide Microzide



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Review of international safety data for lisinopril-hydrochlorothiazide combination treatment.

Murray NH.

Medical Research Department, ICI Pharmaceuticals, Macclesfield, Cheshire, UK.

A total of 930 patients have been evaluated for safety in a programme of clinical trials for lisinopril-hydrochlorothiazide combination treatment. Combination therapy with these two agents is generally well tolerated. In clinical trials, adverse experiences in patients treated with a lisinopril-hydrochlorothiazide combination were dizziness (7.5%), headache (5.2%), cough (3.9%), fatigue (3.7%), orthostatic effects (3.2%), diarrhoea (2.5%), nausea (2.2%) and upper respiratory tract infection (2.2%). Withdrawals from treatment have been relatively infrequent comprising dizziness (0.8%), headache (0.3%), cough (0.6%), fatigue (0.4%), diarrhoea (0.2%), orthostatic effects and nausea (0.1% each). The most common laboratory adverse experiences in patients on therapy with the lisinopril-hydrochlorothiazide combination are: increases in serum glucose, triglycerides, uric acid, serum creatinine, blood urea nitrogen and blood urea; and decreases in serum potassium. However, in individual controlled studies, the addition of lisinopril to treatment with hydrochlorothiazide results in attenuation of some of the potentially adverse metabolic affects of the diuretic. Adverse experiences in the patients treated for periods of 50 weeks or more, the elderly and the renally impaired are similar to those seen in the total population. Overall the available data indicate that a fixed dose combination of lisinopril-hydrochlorothiazide is a well-tolerated therapeutic option in patients with mild-to-moderate hypertension.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1665180&dopt=Abstract hydrochlorothiazide Microzide



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[Hydrochlorothiazide, allopurinol and magnesium oxide in the treatment of recurrent calcium urolithiasis]

[Article in Polish]

Musialik D, Gluszek J, Pieczynska A.

Kliniki Nadcisnienia Tetniczego Instytutu Kardiologii AM, Poznaniu.

The study aimed at presenting own experience in prevention of new urinary calculi in 18 patients with metabolically active calcium urolithiasis treated with hydrochlorothiazide in daily doses of 100 mg (group I) for 2 years, and in 6 patients with the same disease treated with magnesium oxide in daily doses 300 mg twice a day (group II) for average period of 10 months. In 9 patients a new calculus was formed during the treatment with hydrochlorothiazide, in 7 patients no recurrence was noted, and in 2 remaining patients the results were controversial (coral calculus). Therefore, patients were subdivided into group Ia (failure of hydrochlorothiazide therapy), and group Ib (no recurrence noted). Hydrochlorothiazide did not lead to the stable decrease in the saturation of the urine with calcium oxalate in group Ia whereas in group Ib (without recurrence of urolithiasis) the content of calcium oxalate in the urine was significantly lower than that in group Ia after a 2-year treatment with hydrochlorothiazide (p < 0.01) Recurrence of the disease was seen only in one patient of group II, i.e. treated with magnesium oxide. The treatment of the recurrent calcium urolithiasis is justified and efficient in those patients in whom therapy decreases the content of calcium oxalate in the urine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1669148&dopt=Abstract hydrochlorothiazide Microzide



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Effects of nifedipine on renal responses to several diuretic agents in rats.

Rao VS, Fonteles MC.

Department of Physiology and Pharmacology, Federal University of Ceara, Fortaleza, Brazil.

The influence of the dihydropyridine calcium antagonist nifedipine has been studied on the diuretic response to frusemide, acetazolamide and hydrochlorothiazide in water-loaded (25 mL kg-1) conscious rats. Oral administration of nifedipine (10 mg kg-1) markedly inhibited frusemide- and hydrochlorothiazide-induced diuresis as evidenced by a reduction in 5 h urine volume and urinary sodium and potassium elimination. However, it neither significantly enhanced nor limited urine and electrolyte excretion promoted by acetazolamide. Nifedipine, 5 and 10 mg kg-1 but not 1 mg kg-1, significantly (P less than 0.05) inhibited the diuretic response of hydrochlorothiazide. At doses which affect hydrochlorothiazide diuresis (5 and 10 mg kg-1), nifedipine was found to depress the mean arterial pressure by 32% in normotensive rats. These results are of interest in view of the often reported clinical side effect of nifedipine in promoting peripheral oedema in hypertensive patients and its use in combination with a thiazide or loop diuretic.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1682456&dopt=Abstract hydrochlorothiazide Microzide



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The diurnal rhythm of plasma potassium: relationship to diuretic therapy.

Solomon R, Weinberg MS, Dubey A.

Westchester County Medical Center, New York Medical College, Valhalla.

Plasma potassium levels have been implicated in the genesis of cardiac arrhythmias, particularly in patients receiving diuretic therapy. The present study was undertaken to evaluate the stability of plasma potassium levels throughout a 28-h period. Normal volunteers (n = 8) and subjects with essential hypertension (n = 10) were studied in a clinical research center while receiving controlled dietary intakes. Plasma potassium followed a diurnal rhythm in both groups, with a peak level at 12 h and a trough level at 24 h. The average peak-to-trough difference was 0.62 +/- 0.05 mmol/L. Urinary potassium excretion also followed a diurnal rhythm, with the lowest excretory rate during the evening hours, when plasma potassium reached its nadir. Subjects with essential hypertension were restudied after 4 weeks of hydrochlorothiazide (50 mg/day) and then after an additional 4 weeks of hydrochlorothiazide (50 mg/day) and amiloride (5 mg/day). Hydrochlorothiazide alone reduced plasma potassium at all times of measurement without altering the diurnal rhythm. The combination of hydrochlorothiazide and amiloride resulted in higher plasma potassium levels in the morning, but did not significantly affect evening plasma potassium levels. The frequency of hypokalemia (K less than or equal to 3.0 mmol/L) was related to the time at which the plasma potassium was measured. We conclude that plasma potassium undergoes a diurnal rhythm and that diuretics shift this rhythm to uniformly lower values. This rhythm must be considered when defining the frequency of hypokalemia.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1714003&dopt=Abstract hydrochlorothiazide Microzide