Phototoxicity to sulphonamide-derived oral antidiabetics and diuretics: investigations in hairless mice.

The oral antidiabetics glibenclamide, glipizide, glymidine, tolazamide and tolbutamide and the diuretics bemetizide, bendroflumethiazide, benzylhydrochlorothiazide, bumetanide, butizide, furosemide, hydrochlorothiazide, hydroflumethiazide and trichlormethiazide were investigated for phototoxic effects in hairless mice. The back of the animals (hr/hr-c3H/TifBom) was covered with Duoderm dressing, and at the site of two punched out holes 0.05 ml of the test substances at 0.25 mol/l concentration and the solvent alone as control were injected intradermally, respectively. Both test and control sites were irradiated with 6-12 J/cm2 of longwave UVA light from a "Bluelight 2000" apparatus (Hönle, Martinsried, Germany). Skin reactions were read at 24 and 48 h. Compared to the solvent alone, all of the test substances induced reactions (necrosis or oedema)--most frequently seen by macroscopic and histologic investigation and by measurements with a thickness gage. Injection of the test substance or solvent alone without or with subsequent UVA irradiation, as well as UVA alone, did not induce measurable skin changes in this model. Three oral antidiabetics and four diuretics, not yet described to induce photosensitivity in vitro nor in vivo, were detected as potential photosensitizers using our animal model.

Randomised double-blind comparative study of efficacy and safety of hydroflumethiazide and reserpine and chlortalidone and atenolol in the treatment of mild to moderate hypertension in black patients.

This randomised, double-blind study compared the efficacy and safety of a fixed combination of hydroflumethiazide 50 mg and reserpine 0.125 mg (H-R) and chlortalidone 12.5 mg and atenolol 50 mg (C-A) in adult black patients with mild to moderate hypertension (a resting supine diastolic blood pressure (DBP) between 95 and 115 mmHg after a two week placebo washout period). If the DBP did not reach 90 mmHg after four weeks, the dosage was doubled. There were 27 patients in the H-R group and 22 in the C-A group who completed the study. In the H-R group, supine systolic and diastolic BP were reduced from 156.5 (95% confidence intervals 150.1-162.9) and 102.0 (97.5-106.5) mmHg to 137.0 (130.6-143.4) and 87.4 (83.0-91.9) mmHg, respectively. The corresponding values in the C-A group were 154.1 (147.0-161.2) and 103.4 (98.5-108.4) mmHg to 136.4 (129.3-143.5) and 91.2 (86.2-96.1) mmHg, respectively. Normalisation, response and control of DBP was achieved in 88.9, 92.6 and 100% of patients, respectively, in the H-R group, and in 81.8, 95.5 and 95.5% of patients in the C-A group, respectively. The dose was doubled in 14.8% of patients on H-R and 40.1% on C-A. No clinically significant abnormalities in laboratory variables and no serious adverse effects were encountered. Both drugs have been shown to be efficacious and safe in the treatment of mild to moderate hypertension in black patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin action in insulin-dependent diabetics after short-term thiazide therapy.

The influence of short-term thiazide treatment on peripheral tissue and liver sensitivity to insulin in insulin-dependent diabetes mellitus was determined by the euglycemic insulin clamp technique. A sequential three-step hyperinsulinemic clamp was performed in six insulin-dependent diabetics before and after 2 wk of hydroflumethiazide (HFT) administration in a daily dose of 75 mg. Insulin was infused at rates of 0.5, 2.0, and 4.0 mU X kg-1 X min-1, and each dose was given for at least 120 min. Glucose uptake during the last 30 min of each step was almost identical in the two situations (2.7 +/- 0.6 vs. 2.4 +/- 0.5 mg X kg-1 X min-1, 9.6 +/- 0.9 vs. 9.7 +/- 1.2 mg X kg-1 X min-1, and 12.0 +/- 1.3 vs. 12.6 +/- 1.5 mg X kg-1 X min-1). Serum insulin levels were also similar, and blood glucose was kept at 100 +/- 3, 99 +/- 4, and 97 +/- 3 mg/dl before thiazides and at 93 +/- 6, 93 +/- 6, and 94 +/- 6 mg/dl after thiazides. Another five insulin-dependent diabetics were infused with tritiated glucose followed by insulin infusion at two rates: 0.45 and 1.0 mU X kg-1 X min-1. Basal glucose output was comparable before and after thiazides (3.63 +/- 0.24 vs. 2.97 +/- 0.26 mg X kg-1 X min-1), as was the liver response to increasing insulin concentrations. The metabolic state as assessed by HbA1c and fasting blood glucose did not differ in the two experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of thiazides on thyroid parameters in man.

Iodine metabolism and thyroid hormones in blood were studied in 19 men and 11 women who had been treated with thiazides for arterial hypertension from 1 month to 15 years. The results were compared with the findings from age-matched normal controls. No differences were found regarding 24-h 131I-thyroid uptake, thyroid iodide clearance, renal iodide clearance, plasma inorganic iodide, absolute iodine uptake (AIU), serum thyroxine (T4 (D)), resin T3 test (T3U) and TSH after TRH. Twenty-four-hour urinary iodine was higher in the patients treated with diuretics which could be explained by increased iodine intake. The findings of increased serum triiodothyronine (T3 (RIA)) and reverse T3 (rT3) might be due to changes in distribution volume in the thiazide-treated patients. Long-term treatment with thiazides in man do not lead to iodine depletion.