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At least 937 records · Page 52Linked to original sources
PubMed1992

Renal functional response to captopril during diuretic therapy.

Antihypertensive agents may modify the renal effects of angiotensin converting enzyme inhibition (ACEI). This potential interaction, which is important in the diagnosis of renovascular hypertension was studied in two rat models with and without diuretic treatment prior to ACEI. Acute intravenous administration of furosemide or hydrochlorothiazide in one-kidney, one-clamp animals (1K1C) did not change glomerular filtration rate (GFR) or effective renal plasma flow (ERPF). ACEI administration after furosemide and hydrochlorothiazide decreased GFR (p less than 0.001, p less than 0.01) but not ERPF. Chlorothiazide administered to 1K1C prior to ACEI, decreased GFR (p less than 0.02) but not ERPF captopril administration to 1K1C which received hydrochlorothiazide intraperitoneally for 7-10 days decreased GFR (p less than 0.007) and ERPF (p less than 0.02), while two-kidney, one-clamp animals (2K1C) decreased GFR only in the clamped kidney (p less than 0.005). ERPF in 2K1C increased only in the contralateral kidney (p less than 0.01). Without diuretic 1K1C animals decreased GFR and ERPF after ACEI (p less than 0.005, P less than 0.001). In the clamped kidney of 2K1C rats, GFR and ERPF decreased significantly (p less than 0.0005, p less than 0.004) and contralateral kidney ERPF increased (p less than 0.001), but GFR did not. The consequences of ACEI on GFR are similar with or without diuretic. These data suggest that diuretic therapy may not significantly interfere with ACEI evaluation of renovascular hypertension.

Animals↗
PubMed1987

Interactions of diuretics with the peripheral-type benzodiazepine receptor in rat kidney.

The peripheral-type benzodiazepine receptor (PBR) has been autoradiographically localized to the thick ascending limb and early distal tubule. To elucidate further the role of this receptor in kidney function, we have examined the effects of all classes of diuretics on the binding of labeled PBR-specific ligands (R05-4864, PK 11195) to rat kidney membranes (13,000 X g X 10 min). Drugs capable of inhibiting R05-4864 binding by 50% at less than 200 microM included: metolazone (IC50 = 1 microM), indacrinone (IC50 = 42 microM), indapamide (IC50 = 58 microM), hydrochlorothiazide (HCTZ; IC50 = 117 microM) and trichloromethiazide (IC50 = 175 microM). Conversely, diuretics of the loop (e.g., furosemide), K+-sparing (e.g., triamterene), and carbonic anhydrase inhibitor (e.g., acetazolamide) classes exerted no significant effects on R05-4864 binding (IC50S greater than or equal to 1 mM). Inhibition by indacrinone was stereoselective. Thiazide-like compounds inhibited R05-4864 binding with a rank-order of potencies similar to that for their enhancement of in vivo natriuresis (metolazone greater than HCTZ approximately equal to trichlormethiazide greater than chlorothiazide). Scatchard analysis revealed that metolazone, indacrinone, indapamide and HCTZ inhibited R05-4864 binding by reducing Kd, with no effect on maximum binding. The apparent Kd of metolazone for the renal PBR was 3.8 X 10(-7) M. IC50 values of 14 metolazone derivatives for inhibition of R05-4864 binding correlated well (r = .71, P less than .01) with their natriuretic efficacies. PK 11195 binding to digitonin (1.2 mg/mg of protein)-solubilized membranes displayed the same rank-order of, but was twice as sensitive to inhibition by metolazone, indacrinone, indapamide and HCTZ.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Influence of renin levels on the treatment of essential hypertension with thiazide diuretics.

Initial plasma renin activity (PRA) was measured in 213 patients with untreated hypertension before beginning thiazide (chlorothiazide and hydrochlorothiazide) therapy alone to test whether patients with low-renin hypertension exhibited a greater response to diuretic therapy. Diastolic blood pressure response to treatment in the low, mid-range, and high PRA groups did not differ significantly (delta diastolic blood pressure, -13.6 +/- 1.6, -11.6 +/- 1.5, and -10.8 +/- 2.6 mm Hg, respectively). Moreover, eight subjects with the highest PRA values exhibited the same magnitude of decrease in diastolic blood pressure as did the low PRA group (15.0 +/- 4.2 vs 13.6 +/- 1.6, respectively). This study thus provides no evidence for increased sensitivity to diuretic therapy among patients with low-renin essential hypertension.

Adolescent↗
PubMed1987

Diuretic-associated pancreatitis: a collective review and illustrative cases.

Three patients are presented as illustrative examples of severe necrotizing pancreatitis associated with diuretic therapy. The presumed initiating factor was use of a benzothiadiazine (chlorothiazide, hydrochlorothiazide) or phthalimidine (chlorthalidone) diuretic to control hypertension, after the exclusion of other etiologies. We present these illustrative cases and a collective review, emphasizing that pancreatitis associated with these widely prescribed medications can be fatal and may be more common that previously thought.

Acute Disease↗
PubMed1985

Fluoxetine: clinical pharmacology and physiologic disposition.

Fluoxetine (30 mg), administered for 7 days to normal volunteers, produced a 66% inhibition of tritiated serotonin uptake into platelets. Plasma concentrations of fluoxetine correlated positively with inhibition of serotonin uptake. Fluoxetine is well absorbed after oral administration in both the fed and fasted states and demonstrates dose proportionality. Fluoxetine disappears from plasma with a half-life of 1-3 days; its metabolite norfluoxetine has a plasma half-life of 7-15 days. After administration of 14C-fluoxetine, approximately 65% of the administered dose of radioactivity is recovered in urine and about 15% in feces. Fluoxetine, given as a single dose or in multiple doses over 8 days, did not produce significant effects on the plasma disappearance of warfarin, diazepam, tolbutamide, or chlorothiazide. Coadministration of fluoxetine and ethanol did not result in an increase from control values in the blood ethanol levels, nor did it produce significant changes in physiologic, psychometric, or psychomotor activity. Pharmacokinetics of fluoxetine in the elderly and normal volunteers appear to be similar. In addition, pharmacokinetic analyses in patients with varying degrees of renal impairment did not show significant differences from healthy subjects.

Administration, Oral↗
PubMed1985

[Acute drug-induced pancreatitis].

93 publications concerning drug-induced pancreatitis are reviewed. A confirmed causal relationship between drug and acute pancreatitis so far exists only for 8 compounds: azathioprine, chlorothiazide, furosemide, sulfonamides, tetracycline, estrogens, valproic acid and L-asparaginase. There is less convincing, but still suggestive, evidence for a causal relationship with 5 other drugs, namely: corticosteroids, chlorthalidone, ethacrynic acid, phenformin and iatrogenic hypercalcemia. Due to inadequate or contradictory evidence, the link between a number of additional drugs and acute pancreatitis is considered possible, conditional or doubtful. Finally, the scant literature concerning the pathogenesis and histological lesions of drug-induced pancreatitis is briefly reviewed.

Acute Disease↗
PubMed1979

Effect of diuretics on ADP incorporation in kidney mitochondria.

The effect of diuretics on incorporation of ADP in mitochondria isolated from rabbit renal cortex and medulla was examined. Inhibition of incorporation of [14 C]ADP into both types of mitochondria was observed following pretreatment with furosemide, ethacrynic acid and meralluride at high drug concentrations (7.5 x 10-4 M furosemide and ethacrynic acid, 6.4 x 10-3 M meralluride). At lower concentrations (7.5 x 10-5 M furosemide and ethacrynic acid, 6.4 x 10-4 M meralluride), only entry of ADP in medullary mitochondria was inhibited. Chlorothiazide, 1.7 x 10-3 M, did not inhibit incorporation of ADP into either mitochondrial preparation. Atractyloside, a classic inhibitor of ADP-ATP exchange, showed inhibition in both preparations. Furosemide, injected in vivo inhibited incorporation of ADP into medullary but not cortical mitochondria. These results are consistent with the possibility that loop diuretics may reduce tubular sodium reabsorption by inhibiting ADP-ATP exchange across the mitochondrial membrane, thereby depriving active transport processes of ATP. The differential action on cortical and medullary mitochondria by loop diuretics is consistent with their predominant site of action in the tubule and with the different morphologic characteristics of both types of mitochondria.

Adenosine Diphosphate↗
PubMed1979

Study of the renin-angiotensin system in essential hypertension.

320 patients with essential hypertension divided into three groups (minor, medium and major severty) were studied against 50 normal controls. Plasma renin activity (PRA) was estimated in case of normal and low Na intake, furthermore, of low Na intake in association with administration of chlorothiazide, in the recumbent position as well as at the end of 4-hr walk. The hypertensive group of medium severity (Group II) revealed a significant decrease in PRA, compared with the controls and with the hypertensive group of minor severity (Group I), in each period of observation. A significant increase of PRA in response to insulin hypoglycaemia was demonstrable in all three groups and in the controls, but the increase was of significantly lesser degree in Group II than either in the controls or in Group I. The plasma catecholamine concentrations were found lower in Group II than in the controls and in Group I. An elevation of the plasma catecholamine levels was demonstrable in response to insulin hypeglycaemia, but it was of lesser degree in Group II than a Group I and in the controls. The poor responsiveness of the RAS in Group II is attributed to an inadequate adrenergic activity and to an increased mean arterial pressure in that group, but the higher age of patients and longer duration of hypertensive disease, both characteristic of the group of medium severity, may also effect the renin-angiotensin system.

Adolescent↗
PubMed1984

Effect of oral diuretics on pulmonary mechanics in infants with chronic bronchopulmonary dysplasia: results of a double-blind crossover sequential trial.

In a randomized double-blind crossover trial with sequential analysis, the effects of oral diuretics were compared with the effects of placebo on pulmonary mechanics in ten infants with bronchopulmonary dysplasia (BPD). Pulmonary mechanics were measured before and at the end of a week of treatment with oral diuretics (chlorothiazide, 20 mg/kg/dose and spironolactone, 1.5 mg/kg/dose) given twice daily, or placebo. Mean airway resistance decreased 35.3 cm H2O/L/s, mean specific airway conductance increased 0.095 1/L/s/cm H2O, and mean dynamic pulmonary compliance increased 1.74 mL/cm H2O during treatment with diuretics (all P less than .001), but not during treatment with placebo. The infants' rate of weight gain decreased on the first three days of diuretic treatment, but was thereafter comparable with weight gain during treatment with placebo. Fluid intake was similar in infants receiving diuretics and placebo. But, infants receiving diuretics not only had significantly increased urine output, osmolal clearance, and potassium and phosphorus excretion, but these infants also retained less fluid, and, in addition, excreted less calcium than infants receiving placebo. It is concluded that oral diuretics improve lung function in infants with chronic bronchopulmonary dysplasia; however, potassium and phosphorus depletion are potential complications of treatment.

Administration, Oral↗
PubMed1983

Direct effect of metolazone on sodium-dependent transport across the renal brush border membrane.

Studies with clearance and micropuncture techniques indicate that metolazone inhibits transport of sodium and phosphate in the proximal tubule. The present study is focused on transport across the luminal BBM of the proximal tubule to determine whether metolazone has any direct effect on this initial step in transtubular reabsorption. Addition of metolazone (0.01 to 1.00 mM) to isolated renal BBM vesicles caused dose-dependent inhibition (30% to 70%) of the initial uphill phase of Na+ gradient-dependent phosphate transport but did not inhibit the uptake at equilibrium. There were no significant changes in Na+-independent phosphate transport and phosphate transport under nongradient conditions when metolazone was present at 1.0 mM. The initial Na+ gradient-dependent BBM transport of both D-glucose and L-proline was markedly inhibited by 1.0 mM metolazone, indicating the nonspecific inhibitory action of the drug. Metolazone also inhibited efflux of D-glucose and L-proline from vesicles. Neither acetazolamide nor chlorothiazide at 0.1 to 1.0 mM inhibited BBM transport of phosphate, D-glucose, or L-proline. Metolazone did not change significantly BBM transport of Na+, suggesting that inhibition of Na+-dependent transport was not due to major changes in Na+ flux. These in vitro data indicate that metolazone inhibition of phosphate reabsorption in vivo may be due, in part, to a direct effect of metolazone on transport across the BBM of the proximal tubule.

Acetazolamide↗
PubMed1980

Acebutolol in mild to moderate hypertension: a double-blind crossover study.

The effect of acebutolol (Sectral) was compared with that of placebo in 30 patients with mild to moderate hypertension who were receiving a thiazide diuretic. Ten patients did not complete the study. In the remaining 20 patients, acebutolol (mean dose, 910 +/- 408 mg/day) produced significantly greater reduction both in supine and in erect systolic and diastolic blood pressure over 16 weeks than placebo plus chlorothiazide P less than 0.005). Pulse rate also fell significantly. Four patients did not have a consistent reduction in blood pressure. Acebutolol was found to be an effective hypotensive agent with relatively few side effects.

Acebutolol↗
PubMedDate not supplied

Tamoxifen versus ethinyl estradiol in the treatment of postmenopausal women with advanced breast cancer.

In a randomized study, 63 postmenopausal patients with advanced breast cancer were treated with ethinyl estradiol (EE2) or the antiestrogen tamoxifen to compare the efficacy and side effects of both drugs. EE2 was always given in combination with chlorothiazide to prevent fluid retention. Pretreatment characteristics of the patients of both groups did not differ significantly. Objective remissions were achieved in 31% of the EE2-treated patients and in 33% of the tamoxifen-treated patients. The median duration of remission was 12 months (range, 5-32) for the EE2 group and 11 months (range, 5-26) for the tamoxifen group (P greater than 0.1), and the estimated median survival times from the start of treatment were 31 and 25 months, respectively (P greater than 0.1). The best treatment results in both groups were obtained in patients with estradiol receptor-positive tumors and less advanced disease. After therapy was stopped, objective withdrawal responses were observed in EE2- but not in tamoxifen-treated patients. Two patients receiving EE2 had to discontinue treatment because of drug-related liver function impairment. Both patients had cholelithiasis. Two patients in the tamoxifen-treated group discontinued therapy because of nausea. Deep venous thrombosis occurred in one patient receiving EE2, whereas two patients receiving tamoxifen developed superficial thrombophlebitis. Other side effects in both groups of patients, including initial hypercalcemia, were mild. It is concluded that both treatment regimens, EE2 or tamoxifen, are equally effective with respect to induction and duration of remission in postmenopausal patients with advanced breast cancer. Side effects of EE2 therapy appeared to be more serious than those of tamoxifen treatment.

Adult↗
PubMed1977

Carbonic anhydrase inhibitor side effects. Serum chemical analysis.

Multiple serum chemical values were examined in 92 patients with chronic glaucoma who were treated with the carbonic anhydrase inhibitors (CAIs) acetazolamide or methazolamide, seeking relationships between serum composition and symptomatic side effects. Of the 92 patients, 44 complained of a symptom-complex of malaise, fatigue, weight loss, depression, anorexia, and loss of libido, which we have found most commonly to threaten continuation of therapy. Patients who had this symptom complex were significantly more acidotic than those without it. Ten of 24 patients who had chemical evidence of excessive acidosis reported a dramatic alleviation of symptoms when sodium bicarbonate was administered, although their serum CO2-combining power changed little. There was no correlation of the symptom complex with serum potassium concentration, except in a few patients who were simultaneously receiving chlorothiazide diuretics for systemic hypertension and who became frankly hypokalemic.

Acetazolamide↗
PubMed1987

A comparison of combinations of diuretics in nephrotic edema.

The metolazone-furosemide combination of diuretics was compared with the thiazide-furosemide combination in nephrotic patients with edema. Nine patients underwent a crossover, randomized study receiving furosemide (2 mg/kg per dose) and either metolazone (dose varied according to weight) or chlorothiazide (10 mg/kg per dose). An additive natriuretic and diuretic effect was observed after both metolazone and thiazide were combined with furosemide. The use of both types of diuretic combination was associated with marked kaliuresis. These combinations of diuretics seem equally effective in inducing natriuresis and diuresis in edematous nephrotic patients.

Administration, Oral↗
PubMed1987

Suppression of plasma renin activity in a boy with chronic hyperkalemia.

Chronic hyperkalemia (6.8 mmol/L [6.8 mEq/L]) was discovered in a boy, aged 13 years 7 months, with short stature, delayed puberty, and normal blood pressure. Additional studies revealed hyperchloremic metabolic acidosis (serum values: sodium ion, 139 mmol/L [139 mEq/L]; chloride, 113 mmol/L [113 mEq/L]; bicarbonate, 18 mmol/L [18 mEq/L]), a normal glomerular filtration rate, a subnormal renal threshold for bicarbonate reabsorption, and normal serum thyroxine, growth hormone, and cortisol values. Renal excretion of potassium ion was subnormal for the prevailing serum concentration of potassium ion but was increased normally by infusion of sodium sulfate. The serum aldosterone concentration was appropriate for a normokalemic subject, despite marked suppression of plasma renin activity (PRA) (supine/upright: aldosterone, 140/580 pmol/L [5/21 ng/dL]; PRA, 0.0/0.03 ng/L X s [0.0/0.1 ng/mL/h]). Treatment with chlorothiazide and sodium chloride resulted in correction of the abnormal electrolyte concentrations and an increase in linear growth velocity. Serum aldosterone concentrations did not change significantly during treatment, even though the PRA had increased (supine/upright: aldosterone, 110/920 pmol/L [4/33 ng/dL]; PRA, 0.89/2.17 ng/L X s [3.2/7.8 ng/mL/h]). In this patient, we conclude that (1) hyperkalemia was due to inadequate renal excretion of potassium ion; (2) the serum potassium ion concentration was the major stimulus to aldosterone secretion before treatment; (3) suppression of PRA was more likely due to hyperkalemia than to extracellular volume expansion.

Acidosis↗
PubMed1982

Hydrochlorothiazide pharmacokinetics and pharmacologic effect: the influence of indomethacin.

It is known that nonsteroidal antiinflammatory drugs such as indomethacin can attenuate the pharmacologic effect of loop diuretics such as furosemide and ethacrynic acid and that indomethacin may also reduce the pharmacologic response to chlorothiazide. To examine further this potential drug-drug interaction, we administered 50- an 100-mg single oral doses of hydrochlorothiazide with and without indomethacin to 10 healthy, normal subjects. We observed no significant influence of indomethacin to 10 healthy, normal subjects. We observed no significant influence of indomethacin either on the pharmacokinetics of hydrochlorothiazide or the pharmacologic response to this diuretic. The adsorption and disposition of hydrochlorothiazide demonstrate that this drug is rapidly absorbed and produces a diuretic and natriuretic response that peaks at approximately 2 hours after dosing and is essentially terminated 12 hours after dosing. There appeared to be no greater pharmacologic response to the 100-mg than to the 50-mg hydrochlorothiazide dose in the ten subjects in this study.

Adult↗
PubMed1984

Bioavailability of hydrochlorothiazide from tablets and suspensions.

The bioavailability of hydrochlorothiazide was determined following single oral 25-, 50-, 100-, and 200-mg tablet and suspension doses in 12 healthy male volunteers. Plasma and urine levels of hydrochlorothiazide were determined by HPLC. Plasma levels of hydrochlorothiazide were satisfactorily described by a triexponential function. Mean peak plasma levels, Cmax (127-135, 270-280, and 437-490 ng/mL from the 25-, 50-, and 100-mg doses, respectively) were dose proportional, as were areas under plasma profiles, AUC0----36. Mean percentage recovery of unchanged hydrochlorothiazide in 48-h urine samples accounted for 50-59, 54-55, 60-63, and 54-57% of the 25-, 50-, 100-, and 200-mg doses, respectively. There were no significant differences among these values. Correlation coefficients between 48-h urinary recovery of hydrochlorothiazide and the plasma values (Cmax and AUC0----36) for the 25-, 50-, and 100-mg doses were 0.73 and 0.84. There were no differences in the net increases in electrolyte excretion among the treatments during the 0-12-h postdose period. The systematic availability of hydrochlorothiazide, unlike that of chlorothiazide, is dose proportional in the therapeutic range.

Adult↗
PubMed2002

Effect of amphiphilic drugs on the stability and zeta-potential of their liposome formulations: a study with prednisolone, diazepam, and griseofulvin.

Multilamellar liposomes consisting of phosphatidylcholine and incorporating prednisolone (PZ), diazepam (DZ), or griseofulvin (GF) were prepared and characterized. Liposome size, surface charge, and stability (in buffer and serum proteins) were measured for drug-incorporating liposomes and empty liposomes for comparison. The results reveal that for all drugs studied drug incorporation has a substantial effect on the vesicle zeta-potential and stability. Drug-incorporating liposomes have a negative surface charge, while their membrane integrity is significantly higher when compared with that of empty liposomes. Release of DZ from liposomes is induced by dilution. Summarizing, the results of this study demonstrate that the presence of PZ, DZ, or GF in liposome membranes has a significant effect on main vesicle properties and correlates well with those obtained previously for hydrochlorothiazide and chlorothiazide. Thereby, we may conclude that the previously demonstrated effects of the thiazides on liposome properties are not solely related to their structure.

Diazepam↗