Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CHLOROTHIAZIDE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 955 records · Page 53Linked to original sources
PubMed1976

New aspects of human chronopharmacology.

Regular and thus predictable changes in biologic susceptibility and response to a large variety of physical as well as chemical agents can now be viewed as a rather common phenomenon. Chronopharmacology involves both the investigation of drug effects as a function of biologic timing and the investigation of drug effects upon rhythm characteristics. Illustrative examples of circadian chronopharmacolgy in man are discussed, keeping in mind that the objective demonstration of chronopharmacologic facts needs the use of an appropriate methodology. Circadian changes in the effects of various chemical agents have been documented: histamine, sodium salicylate, acetylcholine, halothane, prostaglandine F, reserpine, cyproheptadine, ethanol, insulin, chlorothiazide, oxymetholone, orciprenalin and SCH 1000 (bronchodilators), indomethacin, ACTH, cortisol and various synthetic corticosteroids. (three new concepts have to be considered: a. The Chronokinetic of a Drug. This term includes both rhythmic changes in the drug vioavailability, pharmacokinetic and its excretion. b. The Chronesthesy of a Biosystem to a Drug. i.e. circadian changes in the susceptibility of any biosystem to a drug. c. The Chronergy of a Drug, taking into consideration its chronokinetic and the chronesthesies of the involved organismic biosystems. Chronopharmacology is useful to solve problems of drug optimization, i.e. to enhance the desired effeciency or to reduce its undesired effects. In the human organism (among other animal species) the metabolic fate of a pharmacologic agent (as well as that of a nutrient) is not constant as a function of time. Thus, the chronobiologic approach of pharmacologic phenomena involves a lesser risk of errors and/or false information than the conventional homeostatic approach.

Biological Availability↗
PubMed1977

Bioavailability of two hydrochlorothiazide preparations.

Eight healthy volunteers received hydro-chlorothiazide 75 mg as Dichlotride and Esiderx. Maximal plasma levels were significantly (p less than 0.05) higher after Dichlotride than Esidrex, 512 +- 189 and 376 +- 70ng/ml, respectively. However, the bioavailability of the two brands of hydrochlorothiazide did not differ significantly as judged by comparison of the AUC0 leads to 9h and AUC0 leads to chi, and the urinary recovery of hydrochlorothiazide during 48 hrs.

Adolescent↗
PubMed1992

The role of complement-derived mediators in inflammatory skin diseases.

The complement system represents an important nonspecific skin defense mechanism. Its activation leads to the generation of products that not only help to maintain normal host defenses but also mediate inflammation and tissue injury. Proinflammatory products of complement include large fragments of C3 with opsonic and cell-stimulatory activities (C3b and C3bi), low molecular weight anaphylatoxins (C3a, C4a, and C5a), and membrane attack complex. Among them C5a or its degradation product C5a des Arg seems to be the most important mediator because it exerts a potent chemotactic effect on inflammatory cells. Intradermal administration of C5a anaphylatoxin induces skin changes quite similar to those observed in cutaneous hypersensitivity vasculitis that occurs through immune complex-mediated complement activation. Complement activation is involved in the pathogenesis of the inflammatory changes in autoimmune bullous dermatoses. In pemphigus complement activation by pemphigus antibody in the epidermis seems to be responsible for the development of characteristic inflammatory changes termed eosinophilic spongiosis. In bullous pemphigoid (BP) interaction of basement membrane zone antigen and BP antibody leads to complement activation that seems to be related to leukocytes lining the dermoepidermal junction. Resultant anaphylatoxins not only activate the infiltrating leukocytes but also induce mast cell degranulation which facilitates dermoepidermal separation and eosinophil infiltration. Similar complement activation seems to play a more direct role in the dermoepidermal separation noted in epidermolysis bullosa acquisita and herpes gestationis. Anaphylatoxin generation via the alternative pathway activation under light irradiation is implicated in the development of the immediate erythematous phototoxic reactions induced by such well-known chemicals as porphyrin, chlorothiazide, demethylchlortetracycline, and chlorpromazine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acne Vulgaris↗
PubMed1987

Hypertension in babies following discharge from a neonatal intensive care unit. A 3-year follow-up.

Seventeen babies who developed hypertension (systolic BP greater than 113 mm Hg) after discharge from a neonatal intensive care unit were followed for a period ranging from 6 to 42 months. Five of the babies had an apparent cause for hypertension--one each had coarctation of the aorta, neuroblastoma, renal artery thrombosis, and two ureteropelvic junction obstruction. Umbilical artery catheters had been used in two additional babies. Ten of the babies had no obvious etiology for their hypertension. No prenatal, obstetrical or postnatal factor could be determined that predisposed these babies to hypertension. Sixteen of the babies were treated, 4 by surgical techniques and 12 by drugs--propranolol with or without chlorothiazide. All children treated medically were able to discontinue antihypertensives by 24 months of age. We conclude that follow-up of all babies discharged from the neonatal intensive care unit should include careful monitoring of blood pressure; that such infants may develop hypertension of unknown cause and that hypertension in this patient population is responsive to medication. Additional study is required to determine if babies discharged from neonatal intensive care units are at high risk for developing hypertension and to determine the natural history, prognosis and optimum treatment for the babies.

Female↗
PubMed1987

Renal basolateral membrane anion transporter characterized by a fluorescent disulfonic stilbene.

The fluorescence enhancement of 4,4'-dibenzamido-2,2'-disulfonic stilbene (DBDS) upon binding to membranes was used to examine proximal tubule stilbene binding sites. Equilibrium binding studies of DBDS to renal brush border (BBMV) and basolateral membrane vesicles (BLMV) were performed using a fluorescence enhancement technique developed for red blood cells (A.S. Verkman, J.A. Dix and A.K. Solomon, J. Gen. Physiol. 81:421-449, 1983). In the absence of transportable anions, DBDS bound reversibly to a single class of sites on BLMV isolated from rabbit (Kd = 3.8 microM) and rat (3.2 microM); 100 microM dihydro-4,4'-diisothiocyano-2,2'-disulfonic stilbene (H2DIDS) blocked greater than 95% of binding. H2DIDS inhibitable DBDS binding was not detected using rat or rabbit BBMV. In rabbit BLMV, DBDS Kd doubled with 10 mM SO4, 50 mM HCO3 and 100 mM Cl, but was not altered by Na or pH (6-8). In stopped-flow experiments the exponential time constant for DBDS binding slowed with SO4, HCO3 and Cl, but was unaffected by Na. These results are consistent with competitive binding of DBDS and anions at an anion transport site. To relate DBDS binding data to anion transport inhibition we used 35SO4 uptake to characterize several modes of rabbit BLM anion transport: H/SO4 and Na/SO4 cotransport, and Cl/SO4 countertransport. Each transport process was electroneutral and was inhibited by H2DIDS, furosemide, probenecid, chlorothiazide and DBDS. The apparent KI's for DBDS (3-20 microM) were similar to Kd for DBDS binding. These studies define a class of anion transport sites on the proximal tubule basolateral membrane measurable optically by a fluorescent stilbene.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed2000

The three mechanisms of intracellular chloride accumulation in vascular smooth muscle of human umbilical and placental arteries.

Recordings of membrane potential (Em) and intracellular [Cl-] ([Cl-]i) were made from the smooth muscle of human umbilical and placental arteries, using double-barrelled, ion-sensitive microelectrodes. In both arteries, [Cl-]i was above equilibrium with Em. In the umbilical artery, [Cl-]i was 33.8+/-0.9 mM (+/-SD, n=19) and Em -54.9+/-1.3 mV and in the placental artery respectively 35.1+/-0.7 mM (n=17) and -50.6+/-0.9 mV. In both arteries, [Cl-]i was reduced and Em hyperpolarised significantly by successive additions of 100 microM 4,4'-diisothiocyanatodihydrostilbene-2,2'-disulphonic acid (DIDS), 10 microM bumetanide and 1 mM acetazolamide, thus revealing the presence of Cl-/HCO3- exchange, (Na+K+Cl) cotransport and "pump III". In the presence of all three inhibitors, [Cl-]i was in equilibrium with Em. As in earlier studies on rat arterial smooth and cardiac muscle, pump III was unaffected by DIDS, bumetanide, metolazone and the removal of Na+, partly inhibited by chlorothiazide and fully inhibited by ethacrynic acid. The results are discussed in terms of the possibility that of chloride accumulating systems may regulate vasomotor tone in the foetoplacental unit.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2006

From hyperinsulinaemic hypoglycaemia to ketotic hypoglycaemia: the range of glucose abnormalities in patients born with intrauterine growth retardation.

INTRODUCTION: Newborns with intrauterine growth retardation (IUGR) have multiple risk factors for developing hypoglycaemia. Hyperinsulinism, both transient and prolonged, is one of the major risk factors responsible for the hypoglycaemia observed in some newborns with IUGR. Once the child has progressed beyond the infancy period, the most common cause of hypoglycaemia is ketotic hypoglycaemia. We report our observations of ketotic hypoglycaemia in six children who were born with IUGR and developed hyperinsulinaemic hypoglycaemia (HH) that required treatment with diazoxide and chlorothiazide. RESULTS: In one of these children the ketotic hypoglycaemia was found to be due to growth hormone deficiency; in the remaining five patients, however, no cause for the hypoglycaemia could be found, despite extensive investigations. These observations suggest that ketotic hypoglycaemia may be more common in children with a history of IUGR. Further studies are required to understand why some newborns with IUGR and HH have an increased risk of ketotic hypoglycaemia in childhood. CONCLUSION: Newborns with a history of IUGR and HH have an increased risk of developing ketotic hypoglycaemia in the childhood period.

Blood Glucose↗
PubMed1976

Regression of atherosclerotic stenosing lesions of the renal arteries and spontaneous cure of systemic hypertension through control of hyperlipidemia.

We describe a 49 year old woman with impressive regression of renal artery stenosing atherosclerotic lesions in response to sustained excellent control of hyperlipidemia. Initially, she had high blood pressure necessitating combined drug therapy with chlorothiazide, methyldopa and propranolol, with only moderately satisfactory control. Renal arteriography revealed a 90 per cent stenosing lesion of the right renal artery and 75 per cent narrowing of the left renal artery. Peripheral vein plasma renin was markedly increased at 32 ng/ml. With a combination of cholestyramine and clofibrate, serum lipids were maintained at normal values for several years. Increased blood pressure diminished spontaneously, and the patient has maintained normal blood pressures after discontinuation of antihypertensive therapy. Repeat renal arteriograms showed almost complete regression of the right renal artery lesion and a possible decrease in left renal artery disease. Peripheral vein plasma renin became normal at 3 ng/ml. This case illustrates that sustained control of hyperlipidemia could lead to regression of atherosclerotic nodules and impressive clinical improvement in certain patients.

Arteriosclerosis↗
PubMed1986

Liver carbonic anhydrase and urea synthesis. The effect of diuretics.

In isolated perfused rat liver, urea synthesis is rapid and reversibly inhibited not only by the well-known carbonic anhydrase inhibitors acetazolamide, methazolamide and ethoxzolamide, but also by diuretics, like xipamide, mefruside, chlortalidone, and chlorothiazide. Furosemide was without effect. Similar to findings with isolated perfused rat liver, acetazolamide inhibits urea synthesis from ammonium ions in normal and cirrhotic human liver slices. Inhibition of urea synthesis by xipamide and acetazolamide is accompanied by a 70% decrease of the cellular citrulline content and the tissue levels of 2-oxoglutarate and citrate, suggesting a block of urea synthesis at a step prior to citrulline formation. At a constant extracellular pH (7.4), inhibition of urea synthesis by xipamide, mefruside and acetazolamide was overcome by increasing the extracellular concentrations of HCO3- and CO2 to above twice the normal values. This shows that inhibition of urea synthesis by these diuretics is not due to an unspecific inhibition of one of the urea cycle enzymes but is due to an inhibition of mitochondrial carbonic anhydrase and therefore due to an impaired HCO3- provision for mitochondrial carbamoylphosphate synthesis. It is concluded that the activity of mitochondrial carbonic anhydrase is required for urea synthesis also in human liver and that several diuretics impair urea synthesis by inhibition of mitochondrial carbonic anhydrase. The pathophysiological significance of these data is discussed with respect to the development of diuretics-induced hyperammonemia and alkalosis in liver disease.

Acetazolamide↗
PubMed1990

Identification and pharmacological properties of binding sites for the atypical thiazide diuretic, indapamide.

[3H]Indapamide bound to a single class of binding sites in pig renal cortex membranes with a dissociation constant Kd = 35 +/- 13 nM and a binding site density Bmax = 40 +/- 9 pmol/mg of protein. [3H]Indapamide binding was inhibited by the carbonic anhydrase inhibitor, acetazolamide, and by thiazide diuretics with the following rank order of potency: chlorothiazide greater than hydrochlorothiazide approximately metolazone greater than hydroflumethiazide. The effect of the latter drugs to inhibit [3H]indapamide binding was not related to their activity as thiazide diuretics, but was significantly correlated with their inhibitory effect on carbonic anhydrase II. These results suggest that the major renal binding site of [3H]indapamide is a membrane form of carbonic anhydrase. Inhibition of carbonic anhydrase may play a role in the antihypertensive effect of indapamide.

Animals↗
PubMed1988

Drug-induced pancreatitis.

We reviewed the English-language literature pertaining to drug-induced pancreatitis and attempted to determine whether the reported association between each drug and pancreatitis was valid. The following drugs seem to cause pancreatitis: azathioprine, chlorothiazide and hydrochlorothiazide, oestrogens, frusemide, 6-mercaptopurine, methyldopa, sulphonamides, sulindac, tetracycline and valproic acid. Less convincing but suggestive evidence exists for colaspase, chlorthalidone, combination cancer chemotherapy, cimetidine, cisplatin, corticosteroids, cytosine arabinoside, diphenoxylate, ethacrynic acid, iatrogenic hypercalcaemia, methandienone, metronidazole, nitrofurantoin, pentamidine, phenformin, piroxicam and procainamide. In general, pancreatitis is a very rare complication of treatment with these drugs. The pathogenesis of the pancreatitis is usually obscure, but is probably mediated by an immune response. Certain drugs such as oestrogens cause hypertriglyceridaemia, which in turn may lead to pancreatitis.

Drug-Related Side Effects and Adverse Reactions↗
PubMed2004

Effects of pH and the presence of micelles on the resolution of diuretics by reversed-phase liquid chromatography.

A comparative study on the performance of two RPLC modes on the separation of 18 diuretics with diverse acid-base behaviour (acetazolamide, althiazide, amiloride, bendroflumethiazide, benzthiazide, bumetanide, canrenoic acid, chlorothiazide, chlorthalidone, ethacrynic acid, furosemide, hydrochlorothiazide, piretanide, probenecid, spironolactone, triamterene, trichloromethiazide and xipamide) was carried out. A conventional octadecylsilane column and acidic acetonitrile-water mobile phases, in the absence and presence of micelles of the anionic surfactant sodium dodecyl sulphate (SDS), were used. The effects of pH and the modifiers acetonitrile and SDS on peak asymmetry, efficiency, selectivity, resolution and analysis time, were examined. The comparison of both RPLC modes (aqueous- and micellar-organics) was done using the same processing tools, applying several polynomial and mechanistic equations to describe the retention. The best separations were obtained by maximising the product of peak purities, considering a wide range of experimental conditions. The study illustrates that, despite the theoretical and practical complexity of the problem, the predicted optimal chromatograms can be reproduced experimentally with great accuracy. None of the examined RPLC modes was able to yield baseline separation of the 18 diuretics. However, their selectivity was complementary, being appropriate for different combinations of a smaller number of the assayed diuretics.

Chromatography, Liquid↗
PubMed1996

The evolution of low-dose diuretic therapy: the lessons from clinical trials.

Safe and effective antihypertensive therapy became available in the 1950s with the introduction of thiazide diuretics. Prior to that time, we did have agents that lowered blood pressure but they often needed to be given parenterally and were too poorly tolerated to be used for the treatment of any but those with life-threatening elevations of blood pressure. When thiazide diuretics-first chlorothiazide and then hydrochlorothiazide-became available, it was possible to lower blood pressure in most hypertensives and assess whether that reduction would lead to a reduction in cardiovascular morbidity and mortality. The results of 17 large trials have now made it clear that antihypertensive therapy with regimens based on diuretics and beta blockers reduces cardiovascular events and saves lives. When first introduced, thiazide diuretics were prescribed at doses we now know are excessively high (100-200 mg of hydrochlorothiazide/day), and we have learned that much lower doses, even as little as 12.5 mg of hydrochlorothiazide, are effective. These lower doses will reduce blood pressure and do so with considerably less in the way of metabolic effects. This article will trace the development of antihypertensive therapy and review how data from clinical trials have influenced the recommendations of the Joint National Committees on the Detection, Evaluation and Treatment of Hypertension.

Benzothiadiazines↗
PubMed1999

Urinary thiamine excretion in the rat: effects of furosemide, other diuretics, and volume load.

Long-term furosemide therapy is associated with increased urinary loss of thiamine. To examine the mechanism of furosemide-induced urinary thiamine loss, we measured urinary excretion of thiamine in rats in response to increasing doses of furosemide, acetazolamide, chlorothiazide, amiloride, mannitol, and extracellular fluid (ECF) volume loading by saline infusion. All animals were in normal thiamine balance as reflected by a thiamine pyrophosphate effect (TPPE) of 2.25% +/- 0.60% (mean +/- SEM), and all had normal renal function. Urinary flow increased in response to diuretic administration in a dose-dependent manner, reaching (mean) peak urinary flow rates of 283 to 402 microL/min. Fractional excretion of sodium (FE(Na)) exhibited the same pattern, reaching peak values of 12.3% to 23.2%. Urinary thiamine excretion increased in proportion to the incremental doses of diuretic agents, reaching (mean) maximal values of 7.44 to 9.34 pmol/min, with no significant difference (P = .11) between the various diuretics tested nor in response to saline loading. None of the diuretics tested differed in the effect on thiamine excretion, which was clearly flow dependent and only partially related to fractional sodium excretion. Urinary flow rate, being the single significant predictor, explained 78% (R2 = 0.78) of the variability in thiamine excretion rates. These findings indicate that urinary thiamine loss is caused by a nonspecific, flow-dependent mechanism common to all of the diuretics tested.

Animals↗
PubMed1984

Hydralazine-induced systemic lupus erythematosus presenting as pyoderma gangrenosum-like ulcers.

A 48-year-old white woman who for 3 years had been taking hydralazine, 100 mg three times a day, propranolol, 160 mg twice a day, and chlorothiazide, 500 mg/day, for hypertension suddenly developed rapidly expanding ulcers that looked like pyoderma gangrenosum. Arthralgias, fevers, and occasional shortness of breath were also noted. A pericardial effusion was diagnosed by echocardiography. The antinuclear antibody (ANA) titer on routine mouse liver substrate was initially negative, but the ANA titer was positive (1:1,920) on human epithelioid cell substrate. Antibodies to histones and single-stranded DNA were also elevated. After discontinuing hydralazine, all signs and symptoms cleared over a 4-week period. At the time of discharge the ANA titer had decreased to 1:480.

Antibodies, Antinuclear↗
PubMed1997

Hypokalemic metabolic alkalosis with hypomagnesuric hypermagnesemia and severe hypocalciuria: a new syndrome?

Bartter's and Gitelman's syndromes are characterized by hypokalemia, urinary potassium wasting, elevated plasma renin activity and aldosterone levels, normotension, and prostaglandinuria. They differ in that hypomagnesemia and hypocalciuria are universal in Gitelman's syndrome; 20% of cases of Bartter's syndrome have hypomagnesemia and hypercalciuria. We present a 44-year-old white man referred for hypokalemia. Clinical evaluation was unremarkable. He had hypokalemia (P(K), 2.8 to 3.0 mEq/L), hypochloremic metabolic alkalosis, mild azotemia (serum creatinine, 1.4 to 1.8 mg/dL; creatinine clearance, 59 mL/min), normocalcemia, marked persistent hypocalciuria (FE(Ca), 0.08% to 0.09%), and normal intact parathyroid hormone levels (51 pg/mL) and glucosuria. He had persistent hypermagnesemia (P(Mg), 2.1 to 2.8 mEq/L) with relative hypomagnesuria (FE(Mg), 3.2% to 5.2%) given the level of renal impairment and hypermagnesemia. Supine plasma renin activity and aldosterone levels were high (11 ng/mL/hr and 43 ng/dL, respectively). An excessive dietary intake of magnesium, including medications, was excluded. Studies were performed after withdrawing all medications for 8 days. A maximum water diuresis was established (an oral load of 20 mL/kg; stable Uosm, 120 mOsm/kg), and free water and solute clearances were studied at baseline and after sequential intravenous injections of 125 mg chlorothiazide and 40 mg furosemide. The patient had moderate renal impairment (technetium diethylene triamine pentacetic acid [DTPA] clearance, 35.4 mL/min/1.73 m2) and, in contradistinction to Bartter's and Gitelman's syndromes, sodium and water handling in the thick ascending limb of the loop of Henle and the distal tubule (fractional distal solute reabsorption) was normal, but there was evidence of a defect in the proximal tubule reabsorption (glucosuria, supranormal C(H2O) and high distal delivery). Hypomagnesuria and hypocalciuria appeared to be secondary to an increase in their absorption in the loop of Henle (increased excretion following furosemide). In conclusion, this combination of metabolic abnormalities has never been described. We postulate a proximal tubular defect in the absorption of NaCl leading to hypocalciuria, hypomagnesuria, and potassium wasting. Whether the tubular defect is primary or secondary to a renal parenchymal disease is, however, unclear.

Acute Disease↗
PubMed1987

Liquid chromatographic screening of diuretics in urine.

We describe a liquid chromatographic screening procedure for the detection, in urine, of twelve of the fifteen potassium-depleting diuretics available in Australia. A 2-ml urine sample was acidified with NaH2PO4 (pH 4.1) and extracted with 4 ml ethyl acetate. The sample was cleaned up further by washing with 5 ml Na2HPO4 (pH 7.5). The ethyl acetate was then evaporated to dryness, the residue reconstituted in 100 microliters mobile phase and 5 microliter were injected onto a Merck LiChrosorb RP-18 (5 microns) column. The ultraviolet absorbance of the eluent was monitored at 271 nm for 10 min. The screen was evaluated by giving each of thirty volunteers the lowest recommended dose of one of the diuretics in the study and obtaining urine samples 4, 8 and 24 h after having taken the dose. Twelve diuretics, chlorothiazide, hydrochlorothiazide, quinethazone, chlorthalidone, methyclothiazide, clopamide, frusemide, metolazone, mefruside, bendrofluazide, cyclopenthiazide and bumetanide, were all detectable up to 24 h after a dose. We therefore conclude that the screen would be reliable for the detection of these diuretics in urine.

Chromatography, High Pressure Liquid↗
PubMed2001

Cardiovascular and diuretic activity of kaurene derivatives of Xylopia aethiopica and Alepidea amatymbica.

The extractives, crude and pure, of Alepidea amatymbica (AA) and Xylopia aethiopica (XA) were subjected to bioassay-directed phytochemical examination for potential cardiovascular and diuretic activity. All extractives and derivatives (XA/O, AA/1, xylopic acid, AA/3, AA/4, AA/5, AA/6, XA/1, XA/2, XA/3) displayed low toxicity, with LC(50) 0.5-5.0 ng/ml. For the first time, diterpene kaurenoids were reported to have significant systemic hypotensive and coronary vasodilatory effect accompanied with bradycardia. These effects were attributed to calcium antagonistic mechanism. The diuretic and natriuretic effects found were similar to the effects of chlorothiazide, suggesting inhibition of Na+ and K+ reabsorption in the early portion of the distal tubule. Further experiments are needed to elaborate the exact mechanisms of the hypotensive and diuretic effects of diterpene kaurenoids.

Animals↗