DOCSLIB.ORG

Treatment of Nephrogenic Diabetes Insipidus with Hydrochlorothiazide and Amiloride

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Treatment of Nephrogenic Diabetes Insipidus with Hydrochlorothiazide and Amiloride 548 Arch Dis Child 1999;80:548–552 Treatment of nephrogenic diabetes insipidus with Arch Dis Child: first published as 10.1136/adc.80.6.548 on 1 June 1999. Downloaded from hydrochlorothiazide and amiloride Veronika Kirchlechner, Dieter Y Koller, Reiner Seidl, Franz Waldhauser Abstract Treatment of NDI focuses on the reduction Nephrogenic diabetes insipidus (NDI) is of polyuria to avoid dehydration and hypernat- characterised by the inability of the raemia and therefore on prevention of early kidney to concentrate urine in response to and late onset complications. In 1959, Craw- arginine vasopressin. The consequences ford and Kennedy introduced hydrochlorothi- are severe polyuria and polydipsia, often azide combined with a low sodium intake in the 6 associated with hypertonic dehydration. treatment of NDI, by which a reduction of the Intracerebral calcification, seizures, psy- urine solute load of 20–50% can be expected. chosomatic retardation, hydronephrosis, Long term treatment with hydrochlorothi- and hydroureters are its sequelae. In this azide, however, frequently results in 7 study, four children with NDI were treated hypokalaemia associated with cardiac arrhyth- with 3 mg/kg/day hydrochlorothiazide and mias. Potassium intake itself, required to prevent hypokalaemia, may result in gastro- 0.3 mg/kg/day amiloride orally three times 8 a day for up to five years. While undergo- intestinal complications. ing treatment, none of the patients had In the 1980s, prostaglandin synthesis inhibi- tors (such as indomethacin) were introduced in signs of dehydration or electrolyte imbal- the treatment of NDI. The combination of ance, all showed normal body growth, and indomethacin/hydrochlorothiazide has been there was no evidence of cerebral calcifi- described as being even more eVective than cation or seizures. All but one had normal indomethacin alone in diminishing urine pro- psychomotor development and normal duction by 50–70%.910 However, hypokalae- sonography of the urinary tract. However, mia must still be expected, as well as other normal fluid balance was not attainable severe adverse eVects induced by indometh- (fluid intake, 3.8–7.7 l/m2/day; urine out- 2 acin, such as renal, gastrointestinal, and put, 2.2–7.4 l/m /day). The treatment was haematopoetic complications.11 well tolerated and no side eVects could be Studies by Alon and Chan12 and Knoers and detected. Prolonged treatment with Monnens11 showed that the combination of hydrochlorothiazide/amiloride appears to hydrochlorothiazide/amiloride is as eVective as http://adc.bmj.com/ be more eVective and better tolerated than the previous combination. In addition, no just hydrochlorothiazide. Its eYcacy ap- potassium intake is necessary and patients do pears to be similar to that of not need to suVer the side eVects of indometh- hydrochlorothiazide/indomethacin but acin. without their severe side eVects. However, there is no experience with long (Arch Dis Child 1999;80:548–552) term usage of the combination hydro- chlorothiazide/amiloride in the treatment Keywords: hydrochlorothiazide; amiloride; of NDI.11 13 Here, we describe four children on September 28, 2021 by guest. Protected copyright. nephrogenic diabetes insipidus; long term treatment with NDI being treated with hydrochloro- thiazide/amiloride over a period of one to five Nephrogenic diabetes insipidus (NDI) is a rare years. inherited disease characterised by the failure of the kidney to respond to arginine vasopressin Patients and methods (AVP) because of a receptor or postreceptor PATIENTS defect, despite raised serum concentrations of 1 Case 1 AVP. As a consequence, the kidney produces A boy (currently 4 years and 9 months old) enormous quantities of hypotonic urine. Thus, was admitted to our clinic at the age of 2 patients with NDI have dramatic polyuria and months. Pregnancy and delivery were un- polydipsia, and any episode of additional water eventful, birth weight 3404 g, and birth length Department of loss (fever, diarrhoea, vomiting) may lead to 54 cm. The patient’s history consisted of Pediatrics, University potential life threatening dehydration and polyuria, lack of weight gain, refusal of oral of Vienna, Währinger hypernatraemia, especially in infants and tod- fluid intake, and vomiting. In another hospital, Gürtel 18–20, A-1090 dlers. A strong relation between repeated NDI was suspected and treatment with hydro- Vienna, Austria episodes of hypernatraemic dehydration and V Kirchlechner chlorothiazide initiated. Because of ongoing mental retardation, seizures, and cerebral vomiting the patient was admitted to our D Y Koller 23 R Seidl calcifications has been documented. Fur- department. After discontinuation of hydro- F Waldhauser thermore, the course of NDI may also be com- chlorothiazide we found hypernatraemia, plicated by dilatation of the urinary tract owing polyuria, and decreased urinary osmolality. Correspondence to: to excessive urine production45and by growth The diagnosis was confirmed by fluid restric- Dr Waldhauser. failure, which is thought to be caused by inad- tion and 1-desamino-8-D-arginine vaso- Accepted 9 February 1999 equate energy intake.2 pressin (DDAVP) administration (table 1). Treatment of nephrogenic diabetes insipidus 549 Table 1 Clinical features of patients before treatment with hydrochlorothiazide and amiloroide Arch Dis Child: first published as 10.1136/adc.80.6.548 on 1 June 1999. Downloaded from Serum Serum 24hurine 24 h urine Urine osmolality Urine osmolality Age* sodium potassium volume osmolality before DDAVP after DDAVP Plasma AVP Genetic mutation of V2 receptor Case (months) (mmol/l) (mmol/l) (ml/kg bw) (mmol/l) (mmol/l) (mmol/l) (pg/ml)†‡ gene 1 6 161 4.7 384 83 128 135 3.25 2 5 160 4.7 360 89 190 210 Point mutation ( T975 →A) 3 14 166 6.1 432 118 64 152 3.0 Point mutation ( T727 →G)14 4 33 145 5.8 336 82 82 105 3.1 Point mutation ( T727 →G)14 *At onset of treatment. †While normally rehydrated. ‡Reference values mean (SD) 1.1 (0.6) pg/ml.15 Treatment with hydrochlorothiazide was re- uneventful, birth weight 3090 g, and birth sumed. In the following months, several length 50 cm. At 10 days of age the girl was episodes of fluid refusal and vomiting occurred admitted to another hospital because of and once even hypernatraemia (161 mmol/l) diarrhoea and hypertonic dehydration. Blood and hypokalaemia (2.2 mmol/l) were noticed. culture revealed infection with Escherichia coli Thus, at the age of 6 months amiloride was and antibiotics were administered. Two years added to the treatment. Subsequent examina- later, after delivery of her brother and his diag- tions revealed minor abnormalities (for details nosis of NDI, detailed re-examination for the see below). occurrence of NDI was performed. At normal serum electrolyte concentrations and normal Case 2 serum osmolality, polyuria, and polydipsia with The second patient is a boy who is currently 1 low urinary osmolality (82 mmol/l) were iden- year and 8 months old. He was delivered by tified. Because neither fluid restriction nor caesarean section because of inadequate labour DDAVP resulted in an increase in urine osmo- at 38 weeks of gestation, with a birth weight of lality, the diagnosis of NDI was established and 4148 g and a birth length of 54 cm; parents are confirmed by genetic analysis (table 1).14 not consanguineous. The patient’s history con- After treatment with hydrochlorothiazide for sisted of screaming attacks, agitation, and fever six months, amiloride was added owing to per- from the 2nd day of life. Further examinations sistent hypokalaemia. Since that time, serum revealed hypernatraemia and increased serum electrolyte concentrations have been in the osmolality. After diagnosis of NDI in another normal range continuously and she has shown hospital, treatment with indomethacin was ini- normal growth and weight gain. tiated. However, at the age of two months the boy was admitted to our hospital because of fever and fluid refusal. After discontinuation of METHODS treatment and subsequent fluid restriction, the Diagnosis of NDI diagnosis of NDI was confirmed owing to a After two 24 hour urine collections and assess- lack of response to DDAVP (table 1). Thereaf- ment of fluid intake, fluid was restricted for a ter, treatment with hydrochlorothiazide was period of four to eight hours followed by intra- http://adc.bmj.com/ initiated and amiloride was added at the age of venous application of DDAVP (1 µg for infants 5 months. During the 1st year of life the patient and 2 µg for toddlers). We determined urine had been hospitalised twice as a result of vom- volume and osmolality, as well as serum iting without electrolyte imbalance. His growth electrolyte concentrations and osmolality, be- and weight gain are adequate. fore and after administration of DDAVP (table 1). Case 3 At well hydrated conditions blood was drawn This boy is now 5 years and 11 months old. for the assessment of AVP by means of a on September 28, 2021 by guest. Protected copyright. Pregnancy and delivery were uneventful, birth recently published radioimmunoassay.15 weight 3190 g, and birth length 50 cm. At the Analysis of the vasopressin type 2 (V2) age of 10 days he was first admitted to our hos- receptor gene was performed at the depart- pital because of fever, diarrhoea, and hyper- ment of human genetics, University Children´s tonic dehydration, with a serum sodium Hospital, Nijmegen, the Netherlands.14 concentration of 166 mmol/l, potassium of 6.1 mmol/l, and serum osmolality of 357 mmol/l, whereas urinary osmolality was Treatment and follow up only 64 mmol/l. Despite these data, polyuria For a period of one to five years, we treated the was noticed. Diabetes insipidus centralis was four patients with NDI with a combination of suspected and treatment with DDAVP initi- hydrochlorothiazide (3 mg/kg/day) and amilo- ated. Because the boy continued to suVer from ride (0.3 mg/kg/day) orally three times a day.
Load more

Recommended publications
  • Pediatric Pharmacotherapy
    Pediatric Pharmacotherapy A Monthly Review for Health Care Professionals of the Children's Medical Center Volume 1, Number 10, October 1995 DIURETICS IN CHILDREN • Overview • Loop Diuretics • Thiazide Diuretics • Metolazone • Potassium Sparing Diuretics • Diuretic Dosages • Efficacy of Diuretics in Chronic Pulmonary Disease • Summary • References Pharmacology Literature Reviews • Ibuprofen Overdosage • Predicting Creatinine Clearance Formulary Update Diuretics are used for a wide variety of conditions in infancy and childhood, including the management of pulmonary diseases such as respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD)(1 -5). Both RDS and BPD are often associated with underlying pulmonary edema and clinical improvement has been documented with diuretic use.6 Diuretics also play a major role in the management of congestive heart failure (CHF), which is frequently the result of congenital heart disease (7). Other indications, include hypertension due to the presence of cardiac or renal dysfunction. Hypertension in children is often resistant to therapy, requiring the use of multidrug regimens for optimal blood pressure control (8). Control of fluid and electrolyte status in the pediatric population remains a therapeutic challenge due to the profound effects of age and development on renal function. Although diuretics have been used extensively in infants and children, few controlled studies have been conducted to define the pharmacokinetics and pharmacodynamics of diuretics in this population. Nonetheless, diuretic therapy has become an important part of the management of critically ill infants and children. This issue will review the mechanisms of action, monitoring parameters, and indications for use of diuretics in the pediatric population (1-5). Loop Diuretics Loop diuretics are the most potent of the available diuretics (4).
    [Show full text]
  • Spironolactone Therapy in Infants with Congestive Heart Failure Secondary to Congenital Heart Disease
    Arch Dis Child: first published as 10.1136/adc.56.12.934 on 1 December 1981. Downloaded from Archives of Disease in Childhood, 1981, 56, 934-938 Spironolactone therapy in infants with congestive heart failure secondary to congenital heart disease SUSAN M HOBBINS, RODNEY S FOWLER, RICHARD D ROWE, AND ANDREW G KOREY Division of Cardiology, Department ofPaediatrics, Hospital for Sick Children, Toronto, and Department ofPaediatrics, University of Toronto, Canada SUMMARY The efficacy of treatment with spironolactone for congestive heart failure secondary to congenital heart disease was studied in 21 infants under 1 year of age. All received digoxin and chlorothiazide. In addition, group A (n = 10) was given supplements of potassium and group B (n = 11) received spironolactone. Daily clinical observations of vital signs, weight, hepatomegaly, and vomiting were recorded. Paired t test analysis showed significant reduction in liver size and weight (P< 01) and respiratory rate (P< 0 05) in group B, and less significant decreases in group A. The incidence of vomiting was slightly lower in group B. We conclude that the addition of spiro- nolactone hastens and enhances the response to standard treatment with digoxin and chlorothiazide in infants with congestive heart failure. Spironolactone, a pharmacological antagonist of the We excluded or withdrew from the study any adrenal mineralocorticoid,l has been used for some infant in whom any of the following was present copyright. years in the treatment of congestive heart failure or developed. (1) Renal disease or dysfunction, as (CHF). By competitively binding to specific nuclear shown by blood urea nitrogen >8-925 mmol/l macromolecules in the distal convoluted renal (25 mg/100ml) or hepatic disease or dysfunction.
    [Show full text]
  • Chlorothiazide Versus Metolazone in Hospitalized Patients with Heart
    Chlorothiazide Versus Metolazone in Hospitalized Patients with Heart Failure Receiving Loop Diruetics Barry Nicholson, PharmD; Halley Gibson, PharmD, BCPS Lahey Hospital & Medical Center, Burlington, MA Background Baseline Characteristics Secondary Outcomes Results • Heart failure (HF) is the primary diagnosis in > 1 million hospitalizations annually Characteristic Metolazone Chlorothiazide p-value • Loop diuretics are first-line treatment for edema for most patients with HF, and Secondary Outcome Metolazone Chlorothiazide p-value (n=62) (n=59) thiazide diuretics may be used as an adjuvant option for additional diuresis1 (n=62) (n=59) • Previous trials have shown that oral metolazone is non-inferior to intravenous chlorothiazide with regards to safety and efficacy2,3 Age (years) ± SD 75.6 ± 12.1 74.8 ± 12.1 0.55 Hypokalemia within 24 hours 13 (21) 14 (23.7) 0.89 • There is currently no institution-specific policy to guide thiazide diuretic post-thiazide, n (%) Male, n (%) 40 (64.5) 34 (56.7) 0.55 selection in patients with heart failure at Lahey Hospital & Medical Center Hypokalemia within 72 hours 10 (16.1) 5 (8.5) 0.32 post-thiazide, n (%) Objective Weight (kg) ± SD 92 ± 32.8 95.5 ± 31.1 0.54 To evaluate the safety and efficacy of chlorothiazide versus metolazone for Hypomagnesemia within 24 hours 5 (8.1) 7 (11.9) 0.69 Non-ICU, n (%) 48 (77.4) 39 (65) 0.24 augmented diuresis in hospitalized heart failure patients receiving loop diuretics post-thiazide, n (%) Endpoints Progressive Care Unit, n (%) 12 (19.4) 3 (5.1) 0.07 Hypomagnesemia within 72 hours 9 (14.5) 6 (10.2) 0.66 post-thiazide, n (%) Primary Endpoint Change in net urine output (UOP) pre and post-initiation Intensive Care Unit, n (%) 2 (3.2) 17 (28.8) <0.01* of either study thiazide diuretic at 24 and 72 hours Length of Stay, days ± SD 14.7 ± 6.6 17 ± 11.8 0.2 Serum creatinine, mg/dL ± SD 2.2 ± 1.2 2.2 ± 1.1 0.91 Secondary Endpoints - Incidence of the following at 24 and 72 hours: # patients needing additional 27 (43.5) 37 (62.7) 0.05 1.
    [Show full text]
  • Potassium and Magnesium-Sparing Diuretics
    Originalia Potassium and Magnesium-Sparing Diuretics M. P. Ryan Summary chez i) des rats non anesthesies avec une gebnis entspricht der unterschiedlichen Be­ charge saline ii) la clearance renale chez les handlung von Kalium und Magnesium im The renal handling of potassium and mag­ animaux anesthesies iii) des patients avec distalen Tubulus und im Sammelrohr. nesium and the effects of diuretics on these insuffisance cardiaque congestive chroni­ Auch bei Triamteren wurden magnesium­ processes are reviewed. Loop-blocking que. Dans des etudes sur I'animal, une rela­ sparende Eigenschaften nachgewiesen. Die diuretics cause major losses of both potas­ tion dose-reponse a ete etablie pour les ac­ Wirkungen von Aldosteron-Antagonisten sium and magnesium. Thiazide diuretics tions de I'amiloride dans la reduction de sind allerdings noch nicht so eingehend cause major losses of potassium while their !'excretion fractionnee du Mg et du K au nachgewiesen. effects on magnesium excretion are less well cours de la diurese induite par le furose­ established. Evidence has accumulated in mide. Les effets de l'amiloride sur !'excre­ recent years that the potassium-sparing tion du Mg sont moindres que ceux sur diuretics also exert magnesium-sparing !'excretion du K qui est compatible avec un Introduction properties. Experiments from our own traitement different de K et de Mg dans le laboratories and from other investigators tubule distal et le canal collecteur. L'triam­ Congestive heart failure is a disease are reviewed. Amiloride has been demons­ terene est I'diuretique peuvent avoir aussi trated to exert magnesium-sparing proper­ proprietes d'epargne du Mg. Lcs effets des which may be associated with dis­ ties in i) conscious saline-loaded rats ii) re­ antagonistes de I' aldosterone sur l'excretion turbances in the four main cations nal clearance studies in rats iii) congestive du Mg sont mains bien etablis que ceux de namely sodium, potassium, calcium heart failure patients.
    [Show full text]
  • Should We Switch from Bendrofluazide to Chlorthalidone As the Initial Treatment for Hypertension? a Review of the Available Medication
    ORIGINAL SCIENTIFIC PAPER SYSTEMatic REVIEW Should we switch from bendrofluazide to chlorthalidone as the initial treatment for hypertension? A review of the available medication Bruce Arroll MBChB, PhD, FRNZCGP; Henry Wallace Department of General Practice and Primary ABSTRACT Health Care, University of Auckland, Private Bag INTRODUCTION: Thiazide diuretics are commonly prescribed in the treatment of hypertension. 92019, Auckland 1142, However, thiazide diuretics may not all be equal in their ability to reduce cardiovascular New Zealand disease outcomes. AIM: To determine if bendroflumethiazide/bendrofluazide, the most commonly used diuretic for hypertension in New Zealand, is as effective as other diuretics in terms of cardiovascular disease outcomes. METHODS: Using recent reviews of thiazide-like (chlorthalidone or indapamide) and thiazide-type diuretics (hydrochlorothiazide and bendrofluazide) and a separate search of bendrofluazide, data on cardiovascular disease outcomes was extracted. RESULTS: Nineteen relevant papers with 21 comparisons were found. All thiazide-based diu- retics have been reported in at least one trial showing them to be more effective than placebo for cardiovascular disease outcomes, with the exception of chlorothiazide. There were no comparisons of bendrofluazide alone with other medications, but there were two studies with either bendrofluazide or hydrochlorothiazide compared withb -blockers; however, the pooled relative risk (RR) was not significant (RR = 1.10 (95% CI, 0.84–1.43)). For chlorthalidone, there were four comparisons with other medications, and the summary RR was statistically signifi- cant for cardiovascular disease outcomes (RR = 0.91 (95% CI, 0.85–0.98)). Chlorthalidone was significantly more effective for some cardiovascular disease outcomes when compared with doxazosin, amlodipine and lisinopril.
    [Show full text]
  • A New Diuretic That Does Not Reduce Renal Handling of Uric Acid in Rats, S-8666 Yukio YONETANI, Kazumi IWAKI, Mitsuo ISHII and H
    A New Diuretic That Does Not Reduce Renal Handling of Uric Acid in Rats, S-8666 Yukio YONETANI, Kazumi IWAKI, Mitsuo ISHII and Hiroshi HARADA ShionogiResearch Laboratories, Shionogi & Co., Ltd., Fukushima-ku,Osaka 553, Japan AcceptedJanuary 6, 1987 Abstract-The uric acid-retaining effects of diuretics were studied using sodium restricted spontaneously hypertensive rats. Test agents were administered orally once a day for two weeks. Diuretic thiazides such as trichlormethiazide and hydrochlorothiazide and loop diuretics such as furosemide and indacrinone clearly reduced the renal function for uric acid excretion in treatment which produced major effects such as diuresis, saluresis and hypotension. However, a new diuretic with uricosuric activity, S-8666, developed in our laboratories, had no effect on the renal handling of uric acid at doses which showed major effects similar to those of other diuretics. The results should aid the understanding of the utility of S-8666 as a new diuretic antihypertensive which does not cause hyperuricemia during therapy. The high incidence of hyperuricemia to 8666), which is active in rats and chimpanzees hypertension (1, 2) has required the develop (8). We tried to find whether S-8666 affects ment of a new generation of diuretic anti uric acid excretion at a dose which produces hypertensives, which do not cause hyper a major effect, in comparison with other uricemia. Uricosuric diuretics such as tienilic diuretics. Our findings support the utility of acid (3) and indacrinone (4) have recently S-8666 as a new diuretic antihypertensive been studied as such candidates. However, which does not cause hyperuricemia. the results have shown the need for careful testing (5, 6).
    [Show full text]
  • Amiloride Hydrochloride in Hypertensive Patients
    BRTOsN 422 17 February 1968 MEDICAL JOURNAL Br Med J: first published as 10.1136/bmj.1.5589.422 on 17 February 1968. Downloaded from Amiloride Hydrochloride in Hypertensive Patients J. W. PATERSON,* M.B., B.SC., M.R.C.P.; C. T. DOLLERY, M.B., B.SC., M.R.C.P. RUTH M. HASLAM4t M.B., M.R.C.S., D.C.P., M.C.PATH. Brit. med.J., 1968, 1, 422-423 In man amiloride hydrochloride (MK-870) has been shown to t test (as two patients withdrew from this regimen) were used be an orally effective diuretic which causes a positive potassium to test the significance of the differences between the average balance. It also enhances the saluretic effects of hydrochloro- blood pressures and weights on each regimen. Though the thiazide and ethacrynic acid and in addition prevents the nega- average lying blood pressure on hydrochlorothiazide (146.7/ tive potassium balance caused by these diuretics (Wilson et al., 89.1 mm. Hg) was lower than that on amiloride (152.4/92.2 1966; Gombos et al., 1966). Gombos et al. also studied its mm. Hg) the difference was not significant at the 5% level. effects in 10 hypertensive patients, all of whom were on other The average lying blood pressure on the combination (143.9/ antihypertensive agents. The present study was undertaken to 90.6 mm. Hg) was again not significantly different from that on compare the effect of amiloride hydrochloride with hydro- either diuretic alone. Comparison of the average sitting, stand- chlorothiazide in mild hypertensives who were on no other ing, and exercise blood pressures showed no significant differ- therapy.
    [Show full text]
  • Chlorothiazide) Oral Suspension
    NDA 11-870/S-040 Page 3 DIURIL® (CHLOROTHIAZIDE) ORAL SUSPENSION DESCRIPTION DIURIL* (Chlorothiazide) is a diuretic and antihypertensive. It is 6-chloro-2H-1,2,4-benzothiadiazine­ 7-sulfonamide 1,1-dioxide. Its empirical formula is C7H6ClN3O4S2 and its structural formula is: It is a white, or practically white, crystalline powder with a molecular weight of 295.72, which is very slightly soluble in water, but readily soluble in dilute aqueous sodium hydroxide. It is soluble in urine to the extent of about 150 mg per 100 mL at pH 7. DIURIL Oral Suspension contains 250 mg of chlorothiazide per 5 mL, alcohol 0.5 percent, with methylparaben 0.12 percent, propylparaben 0.02 percent, and benzoic acid 0.1 percent added as preservatives. The inactive ingredients are D&C Yellow 10, flavors, glycerin, purified water, sodium saccharin, sucrose and tragacanth. CLINICAL PHARMACOLOGY The mechanism of the antihypertensive effect of thiazides is unknown. DIURIL does not usually affect normal blood pressure. DIURIL affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosage all thiazides are approximately equal in their diuretic efficacy. DIURIL increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate. After oral use diuresis begins within 2 hours, peaks in about 4 hours and lasts about 6 to 12 hours. Pharmacokinetics and Metabolism DIURIL is not metabolized but is eliminated rapidly by the kidney. The plasma half-life of chlorothiazide is 45-120 minutes. After oral doses, 10-15 percent of the dose is excreted unchanged in the urine.
    [Show full text]
  • And Ethacrynic Acid
    27 November 1965 Gastric Ulceration-Horwich and Galloway BRmsm 1277 The ulcer crater disappeared completely in 81% of the cases Dr. S. Gottfried for his assistance; to Biorex Laboratories Ltd. for Br Med J: first published as 10.1136/bmj.2.5473.1277 on 27 November 1965. Downloaded from after six weeks and in 92 % after 12 weeks of carbenoxolone. supplies of trial tablets and carbenoxolone sodium; to Mr. F. M. Sullivan, of Guy's Hospital Medical School, for his assistance with The dose used in the trial was 100 mg. thrice daily for the the statistical analysis; and to Mr. E. Thomas, Chief Pharmacist, first week and 50 mg. thrice daily for the second and subsequent Whiston Hospital, who distributed the trial tablets. weeks. Treatment should be continued until the ulcer has been shown radiologically to have healed. After complete healing a maintenance dose should be prescribed to prevent recurrence. REFERENCES Attention is also drawn to the drug's side-effects, which Br0chner-Mortensen, K. Krarup, N. B., Meulengracht, E., Videbwk, A. occurred in 35 % of patients, and of which salt-and-water (1955). Brt. med. i., 1, 818. retention is the most important. The side-effects led to the Doll, R., Hill, I. D., Hutton, C., and Underwood, D. J. (1962). Lancet, 2, 793. introduction of a five- or six-day regime in which carbenoxolone Jones, F. A., and Pygott, F. (1958). Ibid., 1, 657. was omitted on one or both days at the week-end in those at - Price, A. V., Pygott, F., and Sanderson, P. H.
    [Show full text]
  • Diuretics in the Treatment of Patients Who Present Congestive Heart Failure and Hypertension
    Journal of Human Hypertension (2002) 16 (Suppl 1), S104–S113 2002 Nature Publishing Group All rights reserved 0950-9240/02 $25.00 www.nature.com/jhh Diuretics in the treatment of patients who present congestive heart failure and hypertension AJ Reyes Institute of Cardiovascular Theory, Montevideo, Uruguay The main operational objective of diuretic therapy in ment natriuresis in patients with congestive heart failure patients who present congestive heart failure and hyper- and hypertension. The state of renal function, the exis- tension is to reduce or to suppress excess bodily fluid. tence of certain co-morbid conditions, potential Effective diuretic therapy decreases cardiac size when untoward drug actions, and possible interactions of the heart is dilated, and it reduces lung congestion and diuretics with nutrients and with other drugs are some excess water. Consequently, external respiratory work of the factors that must be considered at the time of diminishes and cardiac output would be redistributed in deciding on the diuretic drug(s) and dose(s) to be pre- favour of systemic vascular beds other than that of the scribed. Spironolactone has been found to increase life respiratory muscles; dyspnoea decreases markedly and expectancy and to reduce hospitalisation frequency there is a slight reduction in fatigue. This clinical when added to the conventional therapeutic regimen of improvement and the fall in body weight caused by patients with advanced congestive heart failure and sys- diuretics entail an increase in effort capacity. Sub- tolic dysfunction. Therefore, spironolactone should be sequent exercise training ameliorates the abnormal ven- the drug of choice to oppose the kaliuretic effect of a tilatory response to physical effort and the skeletal mus- loop or of a thiazide-type diuretic.
    [Show full text]
  • Product Monograph
    PRODUCT MONOGRAPH ALDACTAZIDE® 25 (spironolactone and hydrochlorothiazide tablets USP) tablets 25mg: 25mg ALDACTAZIDE® 50 (spironolactone and hydrochlorothiazide tablets USP) tablets 50mg: 50mg Aldosterone Antagonist with a Diuretic Pfizer Canada ULC Date of Revision: 17,300 Trans-Canada Highway March 03, 2021 Kirkland, Quebec H9J 2M5 ® TM G.D. Searle LLC Pfizer Canada ULC, Licensee © Pfizer Canada ULC 2021 Submission Control No: 244911 ALDACTAZIDE (spironolactone and hydrochlorothiazide) Page 1 of 39 Table of Contents PART I: HEALTH PROFESSIONAL INFORMATION ........................................................ 3 SUMMARY PRODUCT INFORMATION ....................................................................... 3 INDICATIONS AND CLINICAL USE ............................................................................. 3 CONTRAINDICATIONS .................................................................................................. 4 WARNINGS AND PRECAUTIONS ................................................................................. 5 ADVERSE REACTIONS ................................................................................................. 10 DRUG INTERACTIONS ................................................................................................. 16 DOSAGE AND ADMINISTRATION ............................................................................. 20 OVERDOSAGE ............................................................................................................... 21 ACTION AND CLINICAL PHARMACOLOGY
    [Show full text]
  • Pulmonary Function and Electrolyte Balance Following Spironolactone Treatment in Preterm Infants with Chronic Lung Disease
    Original Article ⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢ Pulmonary Function and Electrolyte Balance Following Spironolactone Treatment in Preterm Infants With Chronic Lung Disease: A Double-Blind, Placebo-Controlled, Randomized Trial David J. Hoffman, MD born infants who receive intermittent positive pressure ventilation.1 Jeffrey S. Gerdes, MD Long-term diuretic therapy is an important component of the care Soraya Abbasi, MD received by premature infants with chronic lung disease.2 The combi- nation of oral chlorothiazide and spironolactone has been shown to OBJECTIVE: decrease mean airway resistance and increase airway conductance To study the effect of spironolactone on dietary electrolyte supplementa- and compliance in premature infants diagnosed with bronchopulmo- 3 tion, pulmonary function, and electrolyte balance in premature infants nary dysplasia. The use of Aldactazide (a 1:1 mixture of spironolac- with chronic lung disease. tone and hydrochlorothiazide), however, did not improve pulmonary mechanics or oxygenation despite the occurrence of a diuresis.4 Fur- STUDY DESIGN ther, potassium depletion is a known complication of diuretic admin- A double-blind, randomized, and placebo-controlled trial was designed to istration. A common medical practice among neonatologists is to add study two groups of low birth weight infants with chronic lung disease at spironolactone to the diuretic regimen to decrease the degree of hypo- Pennsylvania Hospital. The placebo group received chlorothiazide and a kalemia and hyperkaliuria.5 Despite the addition of this potassium- placebo, and the spironolactone group received chlorothiazide and spi- sparing diuretic, many neonates still require dietary supplementation ronolactone during the 2-week study period. A two-tailed t-test was used with potassium chloride and/or sodium chloride.
    [Show full text]