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PubMed1987

Effect of a sustained-release formulation of trimazosin in mild to moderate hypertension.

A single-blind study was conducted to evaluate the blood pressure (BP) reduction and side effects of a sustained-release (SR) formulation of trimazosin in patients with mild to moderate hypertension. Eighteen individuals (age, 21-65 yr; mean diastolic BP, greater than 95 mm Hg) with essential hypertension were enrolled into the study. Each patient's dose was titrated to a range of 150-900 mg/d, with polythiazide added as necessary to achieve BP control. Four hours following the maximum titrated dose of trimazosin, mean standing and supine diastolic BPs were significantly lower than baseline readings. Supine systolic BP and supine and standing heart rate were not significantly lower than baseline. At 24 hours after administration of the maximum dose, there were no significant differences in heart rate of BP compared with baseline readings. Five of 16 patients responded to trimazosin therapy alone. Of the 11 treatment failures with trimazosin alone, five were therapeutic failures and six discontinued because of side effects. Only two of these 11 patients achieved satisfactory results with the combination therapy. Trimazosin SR acutely lowers BP three to six hours after administration. It appears to have a duration of action longer than six hours, but it is not sustained for 24 hours. The proportion of patients failing to respond in this sample was very high and suggests that for similar patients, the drug does not appear to be a very useful antihypertensive agent.

Adult↗
PubMed1983

Trimazosin for the treatment of hypertensive patients failing to respond to thiazides.

In a double-blind study of two populations-one in Birmingham, Alabama, the other in Encinitas, California-a total of 32 hypertensive patients whose blood pressure was not controlled by thiazides alone were evaluated for their response to trimazosin. Patients showing a persistent diastolic blood pressure above 90 mm Hg while receiving 2 mg polythiazide once a day (at Birmingham) or 50 mg hydrochlorothiazide twice a day (at Encinitas) during a baseline 4-week period were randomly assigned to trimazosin and placebo groups. At both clinics, patients had a greater blood pressure response to trimazosin than to placebo in both supine and standing positions. When the data were pooled, the change in supine blood pressure (systolic/diastolic) between the average baseline values and the double-blind period was more than twofold greater for the trimazosin group, a decrease of 12.3/10.9 mm Hg (p less than 0.001). A lesser decrease of 5.4/5.4 mm Hg occurred in the placebo group, significant only for the diastolic pressure (p less than 0.01). Comparative differences between the trimazosin and the placebo groups were more marked for the standing blood pressures, -11.7/-10.0 mm Hg (p less than 0.0001) vs no significant change, +2.3/-2.8 mm Hg, respectively. Little change occurred in the patients' heart rates in either position in either treatment group. Adverse reactions were not clinically important and occurred in about half of the patients in the trimazosin and placebo groups. Therapy was not discontinued in either group because of adverse reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗
PubMed1986

Effects of prazosin, atenolol, and thiazide diuretic on plasma lipids in patients with essential hypertension.

The effects of prazosin and atenolol monotherapy on plasma lipid concentrations were compared in 51 patients with mild to moderate essential hypertension. Prazosin monotherapy (mean dose 5.4 +/- 5.3 mg per day) resulted in a significant decrease in total and low-density lipoprotein cholesterol concentrations; these changes were evident at three months and at six to 12 months. Atenolol monotherapy (mean dose 66 +/- 23 mg per day) resulted in a significant increase in plasma triglyceride concentration that persisted during one year of treatment. The deletion of thiazide from the regimen of prazosin plus thiazide resulted in a small stepwise decrease in plasma triglyceride concentration over 12 months of observation. The addition of polythiazide (0.5 mg two to three times weekly) to the regimen of patients in whom acceptable blood pressure was not attained with prazosin or atenolol monotherapy resulted in a decrease in blood pressure, averaging 18.8 mm Hg for systolic and 10.3 mm Hg for diastolic, and a small, though significant, increase in the concentration of low-density lipoprotein cholesterol. It is suggested that the effects of prazosin on plasma lipid composition may be mediated, at least in part, by blocking an action of either the sympathetic nervous system or circulating catecholamines that normally modulate lipoprotein metabolism and might mediate the lipid alterations induced by thiazide diuretics.

Atenolol↗
PubMed1994

Interaction of benzothiadiazides with human serum albumin studied by dialysis and spectroscopic methods.

The interaction of a series of benzothiadiazides with human serum albumin (HSA) was investigated by equilibrium dialysis (ED) and spectroscopic methods including circular dichroism (CD). The primary binding site of benzothiadiazides was designated site II, the diazepam site on the HSA molecule, as indicated by displacement experiments using different site-selective probes. Tyrosine and lysine amino acid residues were probably involved in the binding site of these compounds to HSA. Both electrostatic and hydrophobic interactions were found to play a role in the binding of these compounds to HSA. Among the compounds tested, chlorothiazide had the highest affinity (K1 = 5.5 x 10(4) M-1, K2 = 5.8 x 10(3) M-1). The primary binding affinity of the compounds for HSA was of the order: chlorothiazide > cyclopenthiazide > polythiazide > ethiazide > trichlormethiazide = methyclothiazde > hydrochlorothiazide. Binding was insensitive to the N-B transition of HSA. The binding site is proposed to consist of a cationic site on the surface of the HSA molecular with a hydrophobic crevice to accommodate the aromatic ring of the compounds. Positions 3 and 7 of the benzothiadiazide molecule is thought to affect the binding affinity to HSA.

Benzothiadiazines↗
PubMed1982

A vasodilator that avoids renin stimulation and fluid retention: antihypertensive treatment with trimazosin.

Trimazosin was given for periods of at least 6 mo to 25 patients with mild to moderate essential hypertension. In doses of 300 to 900 mg dialy trimazosin alone led to blood pressure control (supine diastolic blood pressure less than 90 mm Hg with a fall of at least 10 mm Hg) in 16 patients (64%). Despite the decrements in blood pressure there were no changes in body weight or creatinine clearance. There was also no changes in plasma renin activity or urinary aldosterone excretion rate. Although patients with high control renin values appeared to have greater blood pressure decreases than those with low renin values, responsiveness to treatment was not associated with consistent effects of trimazosin on the renin-angiotensin system. Trimazosin induced a small decrease in plasma total cholesterol concentration. In seven patients whose blood pressures were not controlled by trimazosin alone, the addition of polythiazide led to decreased blood pressure and in five control of pressure was achieved. Thus, trimazosin is an effective antihypertensive when given by itself or in combination with a diuretic. Its mechanism of action has not been established, but its ability to induce vasodilation without concomitant sodium retention or stimulation of the renin axis may be an important factor in its effectiveness.

Adult↗
PubMed2005

Screening procedure for detection of diuretics and uricosurics and/or their metabolites in human urine using gas chromatography-mass spectrometry after extractive methylation.

A gas chromatography-mass spectrometry (GC-MS)-based screening procedure was developed for the detection of diuretics, uricosurics, and/or their metabolites in human urine after extractive methylation. Phase-transfer catalyst remaining in the organic phase was removed by solid-phase extraction on a diol phase. The compounds were separated by GC and identified by MS in the full-scan mode. The possible presence of the following drugs and/or their metabolites could be indicated using mass chromatography with the given ions: m/z 267, 352, 353, 355, 386, and 392 for thiazide diuretics bemetizide, bendroflumethiazide, butizide, chlorothiazide, cyclopenthiazide, cyclothiazide, hydrochlorothiazide, metolazone, polythiazide, and for canrenoic acid and spironolactone; m/z 77, 81, 181, 261, 270, 295, 406, and 438 for loop diuretics bumetanide, ethacrynic acid, furosemide, piretanide, torasemide, as well as the uricosurics benzbromarone, probenecid, and sulfinpyrazone; m/z 84, 85, 111, 112, 135, 161, 249, 253, 289, and 363 for the other diuretics acetazolamide, carzenide, chlorthalidone, clopamide, diclofenamide, etozoline, indapamide, mefruside, tienilic acid, and xipamide. The identity of positive signals in such mass chromatograms was confirmed by comparison of the peaks underlying full mass spectra with reference spectra. This method allowed the detection of the abovementioned drugs and/or their metabolites in human urine samples, except torasemide. The limits of detection ranged from 0.001 to 5 mg/L in the full-scan mode. Recoveries of selected diuretics and uricosurics, representing the different chemical classes, ranged from 46% to 99% with coefficients of variation of less than 21%. After ingestion of the lowest therapeutic doses, furosemide was detectable in urine samples for 67 hours, hydrochlorothiazide for 48 hours, and spironolactone for 52 hours (via its target analyte canrenone). The procedure described here is part of a systematic toxicological analysis procedure for acidic drugs and poisons.

Diuretics↗
PubMed1996

Inhibition of thiazide photohemolysis in vitro by antioxidants and a nitrogen atmosphere.

The diuretics acetazolamide, bemetizide, bendroflumethiazide, benzthiazide, benzylhydrochlorothiazide, bumetanide, butizide, chlorazanile, chlorothiazide, chlortalidone, clopamide, cyclopenthiazide, cyclothiazide, diazoxide, etozoline, furosemide, hydrochlorothiazide, hydroflumethiazide, indapamide, mefruside, metolazone, piretanide, polythiazide, trichlormethiazide, and xipamide were screened in vitro for phototoxic effects by means of a photohemolysis test. In all, 19 out of the 25 test substances revealed phototoxic hemolytic properties after irradiation with either solar stimulating irradiation, UVA and/or visible light. Addition of the antioxidants ascorbic acid, alpha-tocopherole or superoxide dismutase significantly inhibited the phototoxic hemolysis, as well as did investigations carried out in a nitrogen rich atmosphere, findings which indicate the involvement of reactive oxygen species in the phototoxic process.

Antioxidants↗
PubMed1981

Thiazide diuretics inhibit contractions of isolated smooth muscles.

The interaction between thiazide diuretics and contractile responses produced by 5-hydroxytryptamine, acetylcholine, noradrenaline and angiotensin II, has been examined on isolated rat uterus and guinea pig aorta. Hydrochlorothiazide, polythiazide and cyclopenthiazide inhibited the contraction of isolated tissue induced by the spasmogens. These data demonstrated that the tested diuretics possess antagonistic activity on contractions induced by various spasmogens.

Animals↗
PubMed1985

Distal blockade in experimental glomerulonephritis: the role of the diluting segment in sodium retention.

In the light of accumulating evidence implicating the diluting segment as the site of final regulation of sodium excretion by the nephron, we produced in this experiment distal blockade in anti-glomerular basement membrane (GBM) glomerulonephritic (GN) rats by the administration of furosemide and polythiazide. This allowed to dissociate the sodium reabsorption that occurs in the proximal tubule from the one that occurs more distally and permitted an appreciation of the rôle played by the diluting segment in the sodium retention of anti GBM GN. In a previous experiment we showed that GN conscious or anaesthetized rats presented an increase in Na tubular reabsorption and failed to raise their fractional and absolute excretion of sodium as normal one did after rapid volume expansion. In this study distal blockade corrected almost completely the difference in sodium excretion that existed between GN and normal groups before the administration of diuretics, pointing to the important rôle played by the diluting segment in the sodium retention of experimental GN.

Anesthesia↗
PubMed1991

[Tablet strength and dosage of thiazides in hypertension must be reduced].

A number of studies indicate that hydrochlorothiazide doses above 50 mg daily provide little additional hypotensive effect but progressively greater hypokalemic effect. From these and similar studies on other thiazides a daily dose range for thiazides of 12.5-50 mg for hydrochlorothiazide, 1.25-5 mg for bendroflumethiazide, 1-2 mg for trichloromethiazide, 0.5-1 mg for polythiazide, and 6.25-25 mg for chlorthalidone appears to be sufficient. Because amiloride enhances the natriuretic effect of thiazides, this agent has not only a Mg2+/K(+)-sparkling effect, but also a potential thiazide-sparing effect. For this reason, the recommended doses of fixed combinations of hydrochlorothiazide and amiloride should be lowered to the range 6.25 mg/0.625 mg--25 mg/2.5 mg.

Benzothiadiazines↗
PubMed1976

A phase II study of prazosin hydrochloride in hypertensive subjects.

The antihypertensive action of Prazosin was studied in 20 hypertensive patients. Sixteen patients completed the 36-week treatment period. The drug produced a gradual and sustained fall in both systolic and diastolic blood pressure. The dosage used was 1 mg TDS. Only 2 patients required 2 mg TDS of Prazosin combined with 1 mg per day of polythiazide, and one of these did not respond. No postural hypotension or weight gain was observed. Side-effects were mild and were not troublesome.

Adult↗
PubMed1976

An open trial of prazosin in the treatment of hypertension.

An open trial of prazosin has been conducted among 18 males aged 18-68 years (mean 42.7) and 22 females aged 23-70 years (mean 47.5) seen at the Lagos University Teaching Hospital Hypertension Clinic. 3 suffered from mild to moderate hypertension and 9 suffered from severe hypertension. The dose employed ranged from 2 to 60 mg per day in 2 or 3 divided doses. All 6 patients whose placebo diastolic pressure was below 100 mm Hg gave excellent response. 19(76%) of the 25 patients whose placebo diastolic pressure ranged from 100 to 114 mm Hg gave excellent response. Only 3 to 9 patients whose placebo diastolic pressure ranged from 115 to 129 mm Hg gave excellent response. There was improved response when polythiazide 2 mg daily was added to the treatment. The total number giving excellent response increased from 28 (70%) to 36 (90%). In 3 cases (7.5%), the response was fair and one case (2.5%) remained poor. In most cases there was slight increase in pulse rate. The side effects encountered included palpitation in 8 patients 3 of whom also had postural hypotension. There were no biochemical or haematological abnormalities caused by prazosin but on continued therapy 16 patients developed tolerance to its effect. Thus prazusin has been found to be useful addition to the antihypertensive arm amentarium.

Adolescent↗
PubMedDate not supplied

Phototoxicity to sulphonamide derived oral antidiabetics and diuretics. Comparative in vitro and in vivo investigations.

The oral antidiabetics chlorpropamide, glibenclamide, glipizide, gliquiudone, glymidine, tolazamide and tolbutamide, and the diuretics bemetizide, bendroflumethiazide, benzylhydrochlorothiazide, bumetanide, butizide, chlortalidone, furosemide, hydrochlorothiazide, hydroflumethiazide, indapamide, piretanide, polythiazide, trichlormethiazide, and xipamide were investigated for potential phototoxicity in vitro using a cell culture model, and in vivo in hairless mice. After exposure to broad band UVA, the majority of the substances tested in vitro yielded a phototoxic action leading to loss of culture forming ability. In vivo, all tested substances induced edema or ulceration, and lead to a significantly increase in skin fold thickness of the mouse skin. In all, a number of substances not described to induce clinical photosensitivity nor phototoxicity in vitro or in vivo were detected in our testing. When determining potential photosensitizers, it seems important to utilize different test methods, as not all substances will exhibit action in a given assay.

Administration, Oral↗
PubMed1997

Evaluation of phototoxic properties of oral antidiabetics and diuretics. Photohemolysis model as a screening method for recognizing potential photosensitizing drugs.

The oral hypoglycemic drugs carbutamide, chlorpropamide, glibenclamide, glubornuride, gliclazide, glipizide, gliquidone, glisoxepide, glymidine, tolazamide and tolbutamide, and the diuretics acetazolamide, bemetizide, bendroflumethiazide, benzthiazide, benzylhydrochlorothiazide, bumetanide, butizide, chlorazanile, chlorothiazide, chlortalidone, clopamide, cyclopenthiazide, cyclothiazide, diazoxide, etozoline, furosemide, hydrochlorothiazide, hydroflumethiazide, indapamide, mefruside, metolazone, piretanide, polythiazide, trichlormethiazide, and xipamide were investigated for photohemolytic properties in vitro. Irradiation with a SOL 3 apparatus (solar simulating irradiation) revealed hemolysis in the presence of five oral hypoglycemic agents and in the presence of 19 out of the 25 tested diuretics. Photohemolysis was induced in the presence of three substances, respectively, after exposure to UVA or visible light. UVB alone did not induce phototoxic hemolysis in the presence of the tested drugs. Compared to clinical reports on photosensitivity reactions, the photohemolysis model seems a good predictive model in recognizing potential photosensitizing sulfonamides.

Dermatitis, Phototoxic↗
PubMedDate not supplied

Prazosin in hypertension with heart failure.

Prazosin, in daily doses of 6--16 mg, was used along with furosemide and polythiazide in 11 hypertensive heart failure patients. Average supine and standing blood pressures were reduced from 180/108 and 171/106 to 130/84 and 135/86, respectively. Average heart rate decreased from 83 to 73 supine and from 84 to 75 standing. Changes in the indices of cardiac function--indlucing the ejection fraction, ejection time, and apical indices--each indicated improvement of left ventricular function. Thus prazosin along with diuretic agents may be particularly useful in the treatment simultaneously of heart failure and of elevated blood pressure with few side effects.

Adult↗