Thiazide Diuretic Agent
Ruben Vardanyan, Victor Hruby, in Synthesis of Best-Seller Drugs , 2016 Thiazides and thiazide-like diuretics inhibit Na+/Cl cotransporter located on the apical membrane of the early segment of the distal convoluted tubule. They have been widely prescribed for more than 60 years for the treatment of hypertension and various edematous states. Some members of this series retain significant carbonic anhydrase inhibitory activity. They are mild diuretics and effective antihypertensives. Since the introduction of the first representatives of thiazides into medicinal practice in the mid-1950s, decades of criticism and controversy about them has not ceased. But 60 years later, they still remain one of the most important classes of drugs. The thiazide diuretics emerged from efforts to synthesize more potent carbonic anhydrase inhibitors by structural variations of sulfanilamides. A newly synthesized compound, 6-chloro-7-sulfamoyl-2H-l,2,4-benzothiadiazine 1,1-dioxide, displayed much weaker activity as a carbonic anhydrase suppressant than acetazolamide (21.1.1), but it produced a remarkable sodium and chloride excretion with relatively little bicarbonate output. The compound was named chlorothiazide (21.3.1) and became the prototype for a series of effective thiazide series diuretics that include hydrochlorothiazide (21.3.2), hydroflumethiazide (21.3.3), trichlormethiazide (21.3.4), mebutizide (21.3.5), cyclopenthiazide (21.3.6), cyclothiazide (21.3.7), bendroflumethiazide (21.3.8), polythiazide (21.3.9), and methycyclothiazide (21.3.10) (Fig. 21.4.). Thiazide diuretics were the first well-established and tolerated, efficient antihypertensive drugs. As diuretics they are usually used in combination with a loop diuretic to augment the diuresis in patients with refractory edema. Continue reading >>
Paradoxical Antidiuretic Effect Of Thiazides In Diabetes Insipidus: Another Piece In The Puzzle
Diabetes insipidus (DI) is a temporary or chronic disorder characterized by the excretion of excessive quantities of very dilute, but otherwise normal urine. The disease results either from impaired synthesis and secretion of antidiuretic hormone (ADH, vasopressin) by the hypothalamus and posterior pituitary, respectively (central DI), or from an unresponsiveness of the kidneys to the hormone itself (nephrogenic DI) (1–3⇓⇓). The renal water transport defect is located in the collecting system (i.e. the connecting tubule – CNT and the collecting duct – CD) in which vasopressin normally controls the expression and cell surface targeting of the apical water channel aquaporin-2 (AQP2) (4). The CNT and CD are also the site of amiloride-sensitive sodium reabsorption via the epithelial sodium channel (ENaC) (5). Sodium transport across ENaC may osmotically drive transepithelial water reabsorption. Consistently, both AQP2 and ENaC are regulated by vasopressin via V2-receptor-dependent cAMP production (4,5⇓). While exogenous application of vasopressin efficiently corrects the reduced AQP2 expression and the urinary concentration defect in central DI (4), the treatment of nephrogenic DI is usually less obvious and may include different approaches such as dietary sodium restriction, prostaglandin synthesis inhibitors, potassium-sparing diuretics and/or thiazide diuretics (3,6⇓). The use of diuretics for the treatment of a polyuric disease appears paradoxical, but the beneficial effect of thiazides has now been proven for more than 45 yr. In 1959, Crawford and Kennedy showed in a seminal paper that thiazides reduce polyuria and increase urine osmolality in DI (7). Since then, thiazides have become an important component in the therapeutic repertoire for treatment of D Continue reading >>
Treatments for diabetes insipidus aim to reduce the amount of urine your body produces. Depending on the type of diabetes insipidus you have, there are several ways of treating your condition and controlling your symptoms. Cranial diabetes insipidus Mild cranial diabetes insipidus may not require any medical treatment. Cranial diabetes insipidus is considered mild if you produce approximately 3-4 litres of urine over 24 hours. If this is the case, you may be able to ease your symptoms by increasing the amount of water you drink, to avoid dehydration. Your GP or endocrinologist (specialist in hormone conditions) may advise you to drink a certain amount of water every day, usually at least 2.5 litres. However, if you have more severe cranial diabetes insipidus, drinking water may not be enough to control your symptoms. As your condition is due to a shortage of vasopressin (AVP), your GP or endocrinologist may prescribe a treatment that takes the place of AVP, known as desmopressin (see below). Desmopressin Desmopressin is a manufactured version of AVP that's more powerful and more resistant to being broken down than the AVP naturally produced by your body. It works just like natural AVP, stopping your kidneys producing urine when the level of water in your body is low. Desmopressin can be taken as a nasal spray, in tablet form or as a form that melts in your mouth, between your gum and your lip. If you're prescribed desmopressin as a nasal spray, you'll need to spray it inside your nose once or twice a day, where it's quickly absorbed into your bloodstream. If you're prescribed desmopressin tablets, you may need to take them more than twice a day. This is because desmopressin is absorbed into your blood less effectively through your stomach than through your nasal passage Continue reading >>
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Use Of Chlorothiazide In The Management Of Central Diabetes Insipidus In Early Infancy
Copyright © 2017 Manish Raisingani et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Management of central diabetes insipidus in infancy is challenging. The various forms of desmopressin, oral, subcutaneous, and intranasal, have variability in the duration of action. Infants consume most of their calories as liquids which with desmopressin puts them at risk for hyponatremia and seizures. There are few cases reporting chlorothiazide as a temporizing measure for central diabetes insipidus in infancy. A male infant presented on day of life 30 with holoprosencephaly, cleft lip and palate, and poor weight gain to endocrine clinic. Biochemical tests and urine output were consistent with central diabetes insipidus. The patient required approximately 2.5 times the normal fluid intake to keep up with the urine output. Patient was started on low renal solute load formula and oral chlorothiazide. There were normalization of serum sodium, decrease in fluid intake close to 1.3 times the normal, and improved urine output. There were no episodes of hyponatremia/hypernatremia inpatient. The patient had 2 episodes of hypernatremia in the first year of life resolving with few hours of hydration. Oral chlorothiazide is a potential bridging agent for treatment of central DI along with low renal solute load formula in early infancy. It can help achieve adequate control of DI without wide serum sodium fluctuations. 1. Introduction Central diabetes insipidus (DI) refers to the inability to conserve free water and is most commonly caused by hypothalamic/posterior pituitary lesions, resulting in impaired arginine va Continue reading >>
Lithium-induced Diabetes Insipidus: Prevention And Management
Lithium-induced diabetes insipidus: Prevention and management Current Psychiatry. 2013 July;12(7):42-45 John Gideon Searle Professor of Clinical and Translational Pharmacy University of Michigan College of Pharmacy and School of Medicine 1. Ecelbarger CA. Lithium treatment and remodeling of the collecting duct. Am J Physiol Renal Physiol. 2006;291(1):F37-38. 2. Christensen BM, Kim YH, Kwon TH, et al. Lithium treatment induces a marked proliferation of primarily principal cells in rat kidney inner medullary collecting duct. Am J Physiol Renal Physiol. 2006;291(1):F39-48. 3. Francis SG, Gardner DG. Basic and clinical endocrinology. 7th ed. New York, NY: McGraw Hill; 2003:154-158. 4. Stone KA. Lithium-induced nephrogenic diabetes insipidus. J Am Board Fam Pract. 1999;12(1):43-47. 5. Grnfeld JP, Rossier BC. Lithium nephrotoxicity revisited. Nat Rev Nephrol. 2009;5(5):270-276. 6. Wesche D, Deen PM, Knoers NV. Congenital nephrogenic diabetes insipidus: the current state of affairs. Pediatr Nephrol. 2012;27(12):2183-2204. 7. Rose BD, Post TW. Clinical physiology of acid-base and electrolyte disorders. 5th ed. New York, NY: McGraw-Hill; 2001:754-759,782-783. 8. Batlle DC, von Riotte AB, Gaviria M, et al. Amelioration of polyuria by amiloride in patients receiving long-term lithium therapy. N Engl J Med. 1985;312(7):408-414. 9. Earley LE, Orloff J. The mechanism of antidiuresis associated with the administration of hydrochlorothiazide to patients with vasopressin-resistant diabetes insipidus. J Clin Invest. 1962;41(11):1988-1997. 10. Kim GH, Lee JW, Oh YK, et al. Antidiuretic effect of hydrochlorothiazide in lithium-induced nephrogenic diabetes insipidus is associated with upregulation of aquaporin-2, Na-Cl co-transporter, and epithelial sodium channel. J Am Soc Nephrol. 2004;1 Continue reading >>
Amiloride: Physiologic Effects
Amiloride is one of the four potassium sparing diuretics (others include spironolactone, eplerenone, and triamterene). Amiloride is most like triamterene in that they are both cations that directly decrease sodium channel activity in the principal cells in the cortical collecting tubule. Inhibition of sodium reabsorption at the cationic site prevents the secretion of potassium and can lead to life threatening hyperkalemia. The risk of hyperkalemia is higher when it is used concurrently with an ACE inhibitor or another potassium-sparing diuretic (most commonly spironolactone). This class of diuretics is rather weak and is usually used in conjunction with a loop or thiazide diuretic. In addition, amiloride also is a weak inhibitor of cGMP-gated channels; however, this is thought to be fairly weak. An additional use of amiloride involves its importance in patients with lithium-induced nephrogenic diabetes insipidus who have complaints of polyuria and polydipsia. In this circumstance, lithium accumulates in the collecting tubule cells and blocks movement through the sodium channels in the luminal membrane. Blocking these channels with amiloride may partially reverse and even prevent the concentrating effect. Amiloride is the best tolerated drug in its diuretic class and has few side effects aside from hyperkalemia. Continue reading >>
Payperview: Successful Treatment Of Partial Nephrogenic Diabetes Insipidus With Thiazide And Desmopressin - Karger Publishers
Successful Treatment of Partial Nephrogenic Diabetes insipidus with Thiazide and Desmopressin Mizuno H.a Fujimoto S.a Sugiyama Y.a Kobayashi M.a Ohro Y.a Uchida S.b Sasaki S.b Togari H.a Department of Pediatrics, Neonatology and Congenital Disorders Nagoya City University Graduate School of Medical Sciences 1 Kawasumi, Mizuho-cho Mizuho-ku, Nagoya, 467-8601 (Japan) Tel. +81 52 8538246, Fax +81 52 8423449, E-Mail [email protected] I have read the Karger Terms and Conditions and agree. Objective: To clarify whether combination treatment with desmopressin (DDAVP) and thiazide was clinically effective in a patient with congenital nephrogenic diabetes insipidus (CNDI), we evaluated the treatment in a 7-year-old boy with CNDI who had demonstrated a partial response to DDAVP. Method: Both volume of urine and the presence of nocturia were determined during treatment. Result: Neither the usual therapy of a low-salt diet and a thiazide nor intranasal therapy with a large dose of DDAVP was effective. However, combination treatment resulted in a decrease in urinary volume and the disappearance of nocturia. Conclusion: DDAVP coupled with thiazide may be useful for CNDI in patients who have shown a partial response to DDAVP. Reeves WB, Andreoli TE: Nephrogenic diabetes insipidus; in Scriver CR, Beaudel AL, Sly WAS, Valle D (eds): The Metabolic Basis of Inherited Disease, ed 7. New York, McGraw-Hill, 1995, pp 30453070. Hoekstra JA, van Lieburg AF, Monnens LA, Hulstijn-Dirkmaat GM, Knoers VV: Cognitive and psychosocial functioning of patients with congenital nephrogenic diabetes insipidus. Am J Med Genet 1996;61:8188. Continue reading >>
Why Do Thiazides Decrease Polyuria In Diabetes Insipidus?
I was reviewing the treatment of diabetes insipidus the other day, and was reminded of the paradoxical effect of thiazide diuretics on urine output in diabetes insipidus. How does this work? The traditional thinking is that thiazide-induced blockade of the Na-Cl cotransporter in the distal tubule leads to a decrease in GFR. This decrease is compensated by an increase in proximal tubule sodium and water uptake. Because less water and solute are then delivered to the collecting duct, less water is lost as urine. However, some studies suggest that chronic use of thiazides does not result in a decrease in extracellular fluid volume: cardiac output returns to normal several weeks after initiating therapy, and infusion of salt-free dextran does not increase blood pressure. Studies in rats with central DI have also shown that replacement of renal sodium losses does not prevent the antidiuretic effect of thiazides. Experiments by Kim et al. suggest that thiazides may serve to upregulate aquaporin channels and ENaC subunits. In rates with lithium-induced nephrogenic DI, HCTZ reversed lithium-induced downregulation of AQP2. It also caused an increase in the abundance of ENaC channels. While these results are specific to Li-induced renal effects, they may at least partially explain how a thiazide can serve to decrease polyuria in patients with diabetes insipidus. Continue reading >>
Treatment Of Nephrogenic Diabetes Insipidus
INTRODUCTION Nephrogenic diabetes insipidus (nephrogenic DI) results from partial or complete resistance of the kidney to the effects of antidiuretic hormone (ADH). As a result, patients with this disorder are not likely to have a good response to hormone administration (as desmopressin [dDAVP]) or to drugs that increase either the renal response to ADH or ADH secretion. Nephrogenic DI can be hereditary or acquired. In adults, a concentrating defect severe enough to produce polyuria due to nephrogenic DI is most often due to chronic lithium use or hypercalcemia and less frequently to other conditions that impair tubular function, such as Sjögren's syndrome . Release of ureteral obstruction is often associated with a diuresis, but this is short lived and does not require specific therapy other than maintenance fluids. (See "Clinical manifestations and causes of nephrogenic diabetes insipidus" and "Clinical manifestations and diagnosis of urinary tract obstruction and hydronephrosis", section on 'Prognosis and recovery of renal function'.) Hereditary nephrogenic DI, which is largely an X-linked disease, may also be seen by internists since early recognition and treatment in infancy has led to survival to adulthood [2,3]. In addition, affected women may be carriers with few or no symptoms until pregnancy or other stress. In infants with hereditary nephrogenic DI, treatment is aimed at minimizing the polyuria and avoiding hypernatremia and volume depletion. In adults, therapy is usually aimed at correcting the underlying disorder or discontinuing an offending drug. In hypercalcemic patients, for example, normalization of the plasma calcium concentration usually leads to amelioration of polyuria. By contrast, lithium-induced nephrogenic DI may be irreversible if the pati Continue reading >>
How Do Thiazide Diuretics Work?
Hydrochlorothiazide with triamterene (e.g. Hydrene) Indapamide (e.g. Natrilix, Dapa-Tabs, Insig) Each of these drugs in different (they are a different chemical substance) but they way they work in the body is very similar, which is why we group them together as a class of drugs. As thiazide diuretics have a range of effects on the body, both in the kidney and on smooth muscles around the body, they can be used to treat several different health conditions. Your doctor might have prescribed a thiazide diuretic for: Oedema (build up of fluid) with heart failure Oedema (build up of fluid)with hepatic cirrhosis Why do they help with these conditions? Lets take a closer look. The diuretic effect of thiazide diuretics is useful if you have oedema or nephrogenic diabetes insipidus. In a healthy person, the kidneys constantly filter the blood in the body. Most of the blood enters into the nephrons (everything except the big molecules like proteins) and then your body reabsorbs the things you still need, like nutrients and fluids, back into your blood. In the end, only the things your body doesnt need make it to the end of the nephrons and are excreted in your urine. Thiazide diuretics change the reabsorption of certain things in your urine, making you urinate more often. Specifically, they block sodium and chloride salts from being reabsorbed, which means more of these comes out in your urine. Water usually follows sodium in the body to dilute it so if more sodium is excreted, more fluid is excreted, causing the diuretic effect. There are also changes to the reabsorption of potassium and magnesium salts in the body. Hypertension, or high blood pressure, is a health condition that affects many people and is worrying because it increases your risk of cardiovascular events, like Continue reading >>
2 Answers - How Do Thiazides Decrease Urine Volume In Diabetes Insipidus?
How do thiazides decrease urine volume in Diabetes insipidus? Thiazides are Diuretics that act on Distal Convoluted Tubule and inhibit the NaCl cotransporter in the luminal membrane, thus decreasing the Cl and Na+ reabsorption. It has paradoxical antidiuretic action in Diabetes Insipidus (DI) An initial reduction of sodium reabsorption in the distal tubule increases sodium excretion and causes extracellular fluid volume contraction. As a result, the glomerular filtration rate decreases and the proximal tubular sodium and water reabsorption increases. Consequently, less water and sodium are delivered to the collecting tubules and, as a result, less water is excreted. Thiazides work upon the nephrons in kidney usually on the proximal part of the distal tubule. They increase the Sodium excretion and urine volume a by interference with transfer across cell membranes. The result is a reduction in blood volume. Changes in cardiac output and extracellular fluid volume are transient and, in the long-term, the major haemodynamic effect is a reduction in peripheral resistance due to subtle alterations in the contractile responses of vascular smooth muscle. Diabetes insipidus (DI) is a temporary or chronic disorder characterized by the excretion of excessive quantities of very dilute, but otherwise normal urine. In brief thiazides reduce polyuria and increase urine osmolality in DI. Continue reading >>
Diabetes Insipidus Medication: Vasopressin-related Hormones, Antidiabetics, Sulfonylureas, Anticonvulsants, Diuretics, Thiazide, Nonsteroidal Anti-inflammatory Agents (nsaids), Diuretics, Potassium-sparing
Author: Romesh Khardori, MD, PhD, FACP; Chief Editor: George T Griffing, MD more... Treatment for diabetes insipidus (DI) varies with the form of the disorder. In central DI and most cases of gestational DI, the primary problem is a deficiency of antidiuretic hormone (ADH)also known as arginine vasopressin (AVP)and therefore, physiologic replacement with desmopressin is usually effective. A nonhormonal drug can be used if response is incomplete or desmopressin is too expensive. Desmopressin has no role in the treatment of nephrogenic DI or primary polydipsia. Nonhormonal drugs usually are more effective in treating nephrogenic DI. In patients with central DI, replacement of endogenous ADH with exogenous hormones prevents complications of DI and reduces morbidity. Vasopressin has vasopressor and ADH activity. It increases water resorption at collecting ducts (ADH effect). At high doses, it also promotes smooth muscle contraction throughout the vascular bed of renal tubular epithelium (vasopressor effects). However, vasoconstriction is also increased in splanchnic, portal, coronary, cerebral, peripheral, pulmonary, and intrahepatic vessels. Chlorpropamide promotes renal response to ADH. Carbamazepine possibly ameliorates DI by promoting the release of ADH. It is not useful in nephrogenic DI and generally is not a first-line drug. Hydrochlorothiazide is a thiazide diuretic that decreases urinary volume in the absence of ADH. It may induce mild volume depletion and cause proximal salt and water retention, thereby reducing flow to the ADH-sensitive distal nephron. Its effects are additive to those of other agents. Nonsteroidal Anti-inflammatory Agents (NSAIDs) The mechanism of action of NSAIDs is not known, but these agents may act by inhibiting prostaglandin synthesis. Inh Continue reading >>
Thiazide-induced Antidiuresis In Diabetes Insipidus.
Thiazide-induced antidiuresis in diabetes insipidus. This article has been cited by other articles in PMC. Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (440K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References . These references are in PubMed. This may not be the complete list of references from this article. BARLOW ED, DE WARDENER HE. Compulsive water drinking. Q J Med. 1959 Apr;28(110):235258. [ PubMed ] BAER JE, BROOKS AV, NOLL RM, BEYER KH. Effect of hydrochlorothiazide on renal electrolyte gradient in glucose diuresis and experimental diabetes insipidus. J Pharmacol Exp Ther. 1962 Sep;137:319323. [ PubMed ] CRAWFORD JD, KENNEDY GC. Chlorothiazid in diabetes insipidus. Nature. 1959 Mar 28;183(4665):891892. [ PubMed ] Earley LE, Orloff J. THE MECHANISM OF ANTIDIURESIS ASSOCIATED WITH THE ADMINISTRATION OF HYDROCHLOROTHIAZIDE TO PATIENTS WITH VASOPRESSIN-RESISTANT DIABETES INSIPIDUS. J Clin Invest. 1962 Nov;41(11):19881997. [ PMC free article ] [ PubMed ] FRIEDMAN SM, SRETER FA, NAKASHIMA M, FRIEDMAN CL. Adrenal cortex and neurohypophyseal deficiency in salt and water homeostasis of rats. Am J Physiol. 1962 Oct;203:697701. [ PubMed ] HAVARD CW, WOOD PH. Antidiuretic properties of hydrochlorothiazide in diabetes insipidus. Br Med J. 1960 Apr 30;1(5182):13061308. [ PMC free article ] [ PubMed ] JANUSZEWICZ W, HEINEMANN HO, DEMARTINI FE, LARAGH JH. A clinical study of the effects of hydrochlorothiazide on the renal excretion of electrolytes and free water. N Engl J Med. 1959 Aug 6;261(6):264269. [ PubMed ] KENNEDY GC, CRAWFORD JD. A comparison of the effects of adrenalectomy and of chlorothiazide in experimental diabetes insi Continue reading >>
Diuretic, Thiazide (oral Route, Parenteral Route)
Diuretic, thiazide (Oral route, parenteral route) Thiazide or thiazide-like diuretics are commonly used to treat high blood pressure (hypertension). High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled. Thiazide diuretics are also used to help reduce the amount of water in the body by increasing the flow of urine. They may also be used for other conditions as determined by your doctor. Thiazide diuretics are available only with your doctor's prescription. Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not specifically included in product labeling, thiazide diuretics are used in certain patients with the following medical conditions: For patients taking this medicine for diabetes insipidus (water diabetes): Some thiazide diuretics are used in the treatment of diabetes insipidus (water diabetes). In patients with water diabetes, this medicine causes a decrease in the flow of urine and helps the body hold water. Thus, the information given about increased urine flow will not apply to you. Tell your doctor if you have ever had any unusual or allergic reaction to medicines in this group or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods dyes, preservatives, or animals. For non-prescription products, read the label or package ingredien Continue reading >>
Diabetes insipidus (DI) is a condition characterized by large amounts of dilute urine and increased thirst. The amount of urine produced can be nearly 20 liters per day. Reduction of fluid has little effect on the concentration of the urine. Complications may include dehydration or seizures. There are four types of DI, each with a different set of causes. Central DI (CDI) is due to a lack of the hormone vasopressin (antidiuretic hormone). This can be due to damage to the hypothalamus or pituitary gland or genetics. Nephrogenic diabetes insipidus (NDI) occurs when the kidneys do not respond properly to vasopressin. Dipsogenic DI is due to abnormal thirst mechanisms in the hypothalamus while gestational DI occurs only during pregnancy. Diagnosis is often based on urine tests, blood tests, and the fluid deprivation test. Diabetes mellitus is a separate condition with an unrelated mechanism, though both can result in the production of large amounts of urine. Treatment involves drinking sufficient fluids to prevent dehydration. Other treatments depend on the type. In central and gestational disease treated is with desmopressin. Nephrogenic disease may be treated by addressing the underlying cause or the use of a thiazide, aspirin, or ibuprofen. The number of new cases of diabetes insipidus each year is 3 in 100,000. Central DI usually starts between the ages of 10 and 20 and occurs in males and females equally. Nephrogenic DI can begin at any age. The term "diabetes" is derived from the Greek word meaning siphon. Signs and symptoms Excessive urination and extreme thirst and increased fluid intake (especially for cold water and sometimes ice or ice water) are typical for DI. The symptoms of excessive urination Continue reading >>