demeclocycline and Hyponatremia

Hyponatraemia (HN) is the most common electrolyte balance disorder in clinical practice. Since the 1970s, demeclocycline has been used in some countries to treat chronic HN secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH). The precise mechanism of action of demeclocycline is unclear, but has been linked to the induction of nephrogenic diabetes insipidus. Furthermore, the safety profile of demeclocycline is variable with an inconsistent time to onset, and a potential for complications. There has been no systematic evaluation of the use of demeclocycline for the treatment of HN secondary to SIADH to date. A systematic literature review was performed to obtain an insight into the clinical safety and efficacy of demeclocycline for this condition.. Embase(™) , MEDLINE(®) , MEDLINE(®) In-Process, and The Cochrane Library were searched on two occasions using MeSH terms combined with free-text terms. References were screened by two independent reviewers. Relevant publications were then extracted by two independent reviewers, with a third reviewer collating and finalising extractions.. The searches returned a total of 705 hits. 632 abstracts were screened after the removal of duplicates. Following screening, 35 full-length publications were reviewed. Of these, 17 were excluded, resulting in 18 studies deemed relevant for data extraction. Two were randomised controlled trials (RCTs), 16 were non-RCTs, and 10 were case reports.. Although most reports suggest that demeclocycline can address serum sodium levels in specific patients with HN, efficacy is variable, and may depend upon the underlying aetiology. Demeclocycline dose adjustments can be complex, and as its use in clinical practice is not well defined, it can differ between healthcare professionals.. There is a lack of clinical and economic evidence supporting the use of demeclocycline for HN secondary to SIADH. Patients receiving demeclocycline for HN secondary to SIADH must be closely monitored.

Topics: Demeclocycline; Humans; Hyponatremia; Inappropriate ADH Syndrome

Hyponatremia is the most frequent electrolyte disorder in hospitalized patients. Acute and severe hyponatremia can be a life-threatening condition, but recent evidence indicates that also mild and chronic hyponatremia is associated with neurological and extra-neurological signs, such as gait disturbances, attention deficits, falls and fracture occurrence, and bone loss. The syndrome of inappropriate ADH secretion (SIADH) is the most frequent cause of hyponatremia. Hyponatremia secondary to SIADH may result for instance from ectopic release of ADH in lung cancer, from diseases affecting the central nervous system, from pneumonia or other pneumopathies or as a side-effect of various drugs In SIADH, hyponatremia results from a pure disorder of water handling by the kidney, whereas external sodium balance is usually well regulated. Despite increased total body water, only minor changes of urine output and modest oedema are usually seen. Neurological impairment may range from subclinical to life-threatening, depending on the degree and mostly on the rate of serum sodium reduction. The management of hyponatremia secondary to SIADH is largely dependent on the symptomatology of the patient. This review briefly summarizes the main aspects related to hyponatremia and then discusses the available treatment options for the management of SIADH, including vaptans, which are vasopressin receptor antagonists targeted for the correction of euvolemic hyponatremia, such as that observed in SIADH.

Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Blood Volume; Body Water; Chemical and Drug Induced Liver Injury; Clinical Trials as Topic; Demeclocycline; Diabetes Insipidus, Nephrogenic; Disease Management; Drug Interactions; Hospitalization; Humans; Hydrocortisone; Hyponatremia; Hypothyroidism; Inappropriate ADH Syndrome; Kidney Tubules, Collecting; Lithium; Multicenter Studies as Topic; Osmolar Concentration; Paraneoplastic Syndromes; Saline Solution, Hypertonic; Tolvaptan

Hyponatremia is the most common electrolyte disorder. With the aging of the population and the greater propensity of the elderly to develop hyponatremia, this electrolyte disorder is of increasing importance to the practicing nephrologist. In this Attending Rounds, an illustrative patient with hyponatremia is presented. The reasons for the increased incidence and prevalence of hyponatremia in the elderly are discussed, with emphasis on the effects of aging on urinary dilution, the frequently multifactorial nature of hyponatremia in this population, and the absence of a definite cause for inappropriate and persistent vasopressin release in many such patients. The rationale for treating the hyponatremia, even when apparently asymptomatic, is discussed, with attention to cognitive function, gait, and bone structure disturbances that increase the risk for fractures. The various available treatment approaches, including water restriction, demeclocycline, loop diuretics with NaCl supplementation, urea, and vasopressin antagonists are summarized, with emphasis on the efficacy and limitations of each of these therapies.

Topics: Age Factors; Aged; Antidiuretic Hormone Receptor Antagonists; Biomarkers; Chronic Disease; Demeclocycline; Drinking; Female; Hormone Antagonists; Humans; Hyponatremia; Predictive Value of Tests; Risk Factors; Sodium; Sodium Chloride; Sodium Potassium Chloride Symporter Inhibitors; Treatment Outcome; Urea; Urination; Water-Electrolyte Balance

Disorders of sodium [Na+] and water metabolism are commonly encountered in the hospital setting due to the wide range of disease states that can disrupt the balanced control of water and solute intake and output. In particular, the prompt identification and appropriate management of abnormally low serum [Na+] is critical if we are to reduce the increased morbidity and mortality that accompany hyponatremia in hospitalized patients. Use of an algorithm that is based primarily on the symptomatology of hyponatremic patients, rather than the serum [Na+] or the chronicity of the hyponatremia, will help to choose the correct initial therapy in hospitalized hyponatremic patients. However, careful monitoring of serum [Na+] responses is required in all cases to adjust therapy appropriately in response to changing clinical conditions. Although this approach will enable efficacious and safe treatment of hyponatremic patients with syndrome of inappropriate antidiuretic hormone secretion (SIADH) at the present time, evolving knowledge of the consequences of chronic hyponatremia will likely alter treatment indications and guidelines in the future.

Topics: Algorithms; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Consciousness Disorders; Demeclocycline; Disease Management; Diuresis; Extracellular Fluid; HIV Infections; Humans; Hyponatremia; Iatrogenic Disease; Inappropriate ADH Syndrome; Inpatients; Mineralocorticoids; Natriuresis; Neoplasms; Osmolar Concentration; Pneumonia; Saline Solution, Hypertonic

Etiopathogenesis, diagnostics and therapy of hyponatremias are summarized for clinicians. Hyponatremia is the most common electrolyte abnormality. Mild to moderate hyponatremia and severe hyponatremia are found in 15-30% and 1-4% of hospitalized patients, respectively. Pathophysiologically, hyponatremias are classified into two groups: hyponatremia due to non-osmotic hypersecretion of vasopressin (hypovolemic, hypervolemic, euvolemic) and hyponatremia of non-hypervasopressinemic origin (pseudohyponatremia, water intoxication, cerebral salt wasting syndrome). Patients with mild hyponatremia are almost always asymptomatic. Severe hyponatremia is usually associated with central nervous system symptoms and can be life-threatening. Diagnostic evaluation of patients with hyponatremia is directed toward identifying the extracellular fluid volume status, the neurological symptoms and signs, the severity and duration of hyponatremia, the rate at which hyponatremia developed. The first step to determine the probable cause of hyponatremia is the differentiation of the hypervasopressinemic and non-hypervasopressinemic hyponatremias with measurement of plasma osmolality, glucose, lipids and proteins. For further differential diagnosis of hyponatremia, the determination of urine osmolality, the clinical assessment of extracellular fluid volume status and the measurement of urine sodium concentration provide important information. The most important representative of euvolemic hyponatremias is SIADH. The diagnosis of SIADH is based on the exclusion of other hyponatremic conditions; low plasma osmolality (<275 mosmol/kg) and inappropriate urine concentration (urine osmolality >100 mosmol/kg) are of pathognomic value. Acute (<48 hrs) severe hyponatremia (<120 mmol/l) necessitates emergency care with rapid restoration of normal osmotic milieu (1 mmol/l/hr increase rate of serum sodium). Patients with chronic symptomatic hyponatremia have a high risk of osmotic demyelination syndrome in brain if rapid correction of the plasma sodium occurs (maximal rate of correction of serum sodium should be 0.5 mmol/l/hr or less). The conventional treatments for chronic asymptomatic hyponatremia (except hypovolemic patients) include water restriction and/or the use of demeclocycline or lithium or furosemide and salt supplementation. Vasopressin receptor antagonists have opened a new forthcoming therapeutic era. V2 receptor antagonists, such as lixivaptan, tolvaptan, satavaptan and the V2+

Topics: Antidiuretic Hormone Receptor Antagonists; Azepines; Benzamides; Benzazepines; Blood Volume; Brain Diseases; Central Nervous System; Chronic Disease; Demeclocycline; Demyelinating Diseases; Diagnosis, Differential; Diuretics; Extracellular Fluid; Furosemide; Humans; Hyponatremia; Inappropriate ADH Syndrome; Lithium Compounds; Morpholines; Osmolar Concentration; Osmosis; Pyrroles; Severity of Illness Index; Sodium; Spiro Compounds; Time Factors; Tolvaptan; Vasopressins

Hyponatremia is a common electrolyte disorder among hospitalized patients and has been associated with increased mortality. Most patients are asymptomatic, but many do present with symptoms, usually of a generalized neurologic nature. Based-on medical history, physical examination (including volume-status assessment), and laboratory tests, patients can be classified as having either hypervolemic, euvolemic, or hypovolemic hyponatremia. Management depends on the speed of hyponatremia onset; its degree, duration, and symptoms; and whether there are risk factors for neurologic complications. The risks of overly rapid correction must be weighed against the benefits of treating hyponatremia. Traditional therapies have significant limitations. New agents that antagonize arginine vasopressin at the V2 receptor or both the V(1A) and V2 receptors show promise for treating hypervolemic and euvolemic hyponatremia, as they induce desired free water diuresis without inducing sodium excretion.

Topics: Acute Disease; Algorithms; Demeclocycline; Diuretics; Humans; Hyponatremia; Lithium Compounds; Risk Assessment

The authors seek to extend understanding and treatment of hospitalized schizophrenics presenting with complications of polydipsia and dilutional hyponatremia. Attending physicians may ask the consultation/liaison psychiatrist to see schizophrenics with hyponatremically-induced delirium or other psychiatric syndromes. The referring physician may or may not have identified polydipsia and dilutional hyponatremia and their complications. This article will help the consultation/liaison psychiatrist recognize early evidence of water imbalance, describe evaluation, and provide somatic and behavioral treatment approaches to this life-threatening syndrome.. Over the past ten years, the authors have treated more than 100 patients with the polydipsia-hyponatremia syndrome. The authors discuss their and others' experience with drugs that help and hinder patients suffering from dilutional hyponatremia. They review current key articles from the polydipsia-hyponatremia syndrome literature including articles identified via Medline search 1985-94.. Schizophrenics with the polydipsia-hyponatremia syndrome most commonly present with polydipsia, polyuria, urinary incontinence, cognitive, affective, and behavioral changes, seizures, or coma. Quantitating polydipsia, hyponatremia, and diurnal changes in body weight facilitate therapeutic interventions. Treatment include patient and caregiver education, drug therapies to better treat psychosis and better treat osmotic dysregulation, behavioral interventions to interdict polydipsia, and diurnal weight monitoring.. Once recognized, acute, subacute, and chronic complications of the polydipsia-hyponatremia syndrome are readily treatable. Besides treating the patient, consultation/liaison psychiatrists can teach their medical colleagues about this syndrome. In so doing, they will enhance the quality of their patients' lives and help the internist and surgeon feel more comfortable when working with schizophrenics.

Topics: Angiotensin II; Anti-Inflammatory Agents, Non-Steroidal; Antipsychotic Agents; Carbamazepine; Cognition Disorders; Demeclocycline; Drinking Behavior; Electroconvulsive Therapy; Humans; Hyponatremia; Lithium; Mood Disorders; Naloxone; Phenytoin; Polyuria; Propranolol; Psychiatry; Psychotherapy; Schizophrenia; Sodium Chloride; Syndrome; Water Intoxication; Workforce

The etiology, pathophysiology, clinical features, diagnosis, and medical treatment of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are reviewed. SIADH is a common cause of hyponatremia in hospitalized patients. Increased concentrations of antidiuretic hormone (ADH) result in retention of free water, increased excretion of sodium, and hyponatremia. Symptoms generally occur only when hyponatremia is severe (less than or equal to 125 meq/L) and may include anorexia, vomiting, and confusion, followed by seizures, coma, and death. SIADH may result from a variety of diseases, as well as from the use of drugs such as chlorpropamide, carbamazepine, diuretics, and some antineoplastic agents. Diagnosis of SIADH is confirmed by demonstration of a high urine osmolality with a low plasma osmolality, in the absence of diuretic use. Immediate treatment of the symptomatic patient with SIADH includes intravenous furosemide and 3% sodium chloride injection to produce a negative free-water balance. If the underlying cause of SIADH cannot be corrected, the treatment of choice for chronic SIADH is fluid restriction. If this is not tolerated by the patient, demeclocycline can be used to induce a negative free-water balance. Urea, lithium, phenytoin, and loop diuretics have been reported to be effective, but there are few data to support their use. Future research into the treatment of SIADH must be directed at developing effective antagonists of ADH. Treatment of SIADH consists of elimination of underlying causes and restriction of fluid intake; if these measures are unsuccessful or poorly tolerated, long-term drug therapy may be indicated.

Topics: Demeclocycline; Drug-Related Side Effects and Adverse Reactions; Humans; Hyponatremia; Inappropriate ADH Syndrome; Lithium; Urea

Topics: Demeclocycline; Humans; Hyponatremia; Vasopressins

Topics: Animals; Body Water; Demeclocycline; Diuretics; Humans; Hyponatremia; In Vitro Techniques; Kidney Tubules; Lithium; Structure-Activity Relationship; Vasopressins

Topics: Adult; Demeclocycline; Double-Blind Method; Female; Humans; Hyponatremia; Male; Middle Aged; Schizophrenia; Thirst

Eight patients (7 men and 1 woman, mean age 43.1 +/- 8.9 years) with psychosis, intermittent hyponatremia, and polydipsia (PIP syndrome) underwent treatment with demeclocycline in an effort to normalize serum sodium levels and thereby protect the PIP patients against complications including hyponatremic seizures and coma. There tended to be an improvement (p = .080) in early morning serum sodium following treatment with demeclocycline (baseline 132.6 +/- SD 3.3 and treatment serum sodium 134.8 +/- SD 3.3 mEq/1). At the same time, there was an increase (p = .043) in urinary specific gravity following treatment with demeclocycline (baseline 1.0047 +/- SD .0029 and treatment urinary specific gravity 1.0063 +/- SD .0026). Clinical indications for and potential mechanisms of action of demeclocycline treatment in the PIP syndrome are discussed.

Topics: Adult; Clinical Trials as Topic; Demeclocycline; Drinking; Female; Humans; Hyponatremia; Male; Middle Aged; Psychotic Disorders; Sodium; Syndrome

The activity of demeclotetracyclin, and ADH antagonist, is studied in 11 ethylic patients with cirrhosis of the liver, under a large hydric diet (1500 cm3). The prescription of the cyclin (600 mg daily) is always determined by a fall of the urinary osmolarity (-36%) and by a dramatic improvement of the free water clearance (+ 60%); consecutively, we observe an increase of natremia in 8 out of 9 cases. Associated with Spironolactone (200 mg daily) the anti-ADH activity persists (the free water clearance becomes positive in 5 out of 10 patients), in spite of the natriuretic activity of anti-aldosterone ; a minimal fall of the natremia is observed in only 2 cases. The indication of Demeclotetracyclin in the curative or preventive treatment of the hyponatremia of the liver cirrhosis is discussed.

Topics: Adult; Aged; Ascites; Clinical Trials as Topic; Demeclocycline; Drug Therapy, Combination; Edema; Female; Humans; Hyponatremia; Liver Cirrhosis; Male; Middle Aged; Natriuresis; Spironolactone; Vasopressins

Hyponatraemia is a very common medical condition that is associated with multiple poor clinical outcomes and is often managed suboptimally because of inadequate assessment and investigation. Previously published guidelines for its management are often complex and impractical to follow in a hospital environment, where patients may present to divergent specialists, as well as to generalists.. A group of senior, experienced UK clinicians, met to develop a practical algorithm for the assessment and management of hyponatraemia in a hospital setting. The latest evidence was discussed and reviewed in the light of current clinical practicalities to ensure an up-to-date perspective. An algorithm was largely developed following consensus opinion, followed up with subsequent additions and amendments that were agreed by all authors during several rounds of review.. We present a practical algorithm which includes a breakdown of the best methods to evaluate volume status, simple assessments for the diagnosis of the various causes and a straightforward approach to treatment to minimise complexity and maximise patient safety.. The algorithm we have developed reflects the best available evidence and extensive clinical experience and provides practical, useable guidance to improve patient care.

Topics: Algorithms; Anti-Bacterial Agents; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Demeclocycline; Fluid Therapy; Hospitalization; Humans; Hyponatremia; Inappropriate ADH Syndrome; Practice Guidelines as Topic; Tolvaptan; Water-Electrolyte Imbalance

Topics: Algorithms; Anti-Bacterial Agents; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Demeclocycline; Fluid Therapy; Humans; Hyponatremia; Inappropriate ADH Syndrome

Topics: Algorithms; Anti-Bacterial Agents; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Demeclocycline; Fluid Therapy; Humans; Hyponatremia; Inappropriate ADH Syndrome

Binding of vasopressin to its type 2 receptor in renal collecting ducts induces cAMP signaling, transcription and translocation of aquaporin (AQP)2 water channels to the plasma membrane, and water reabsorption from the prourine. Demeclocycline is currently used to treat hyponatremia in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Demeclocycline's mechanism of action, which is poorly understood, is studied here. In mouse cortical collecting duct (mpkCCD) cells, which exhibit deamino-8-D-arginine vasopressin (dDAVP)-dependent expression of endogenous AQP2, demeclocycline decreased AQP2 abundance and gene transcription but not its protein stability. Demeclocycline did not affect vasopressin type 2 receptor localization but decreased dDAVP-induced cAMP generation and the abundance of adenylate cyclase 3 and 5/6. The addition of exogenous cAMP partially corrected the demeclocycline effect. As in patients, demeclocycline increased urine volume, decreased urine osmolality, and reverted hyponatremia in an SIADH rat model. AQP2 and adenylate cyclase 5/6 abundances were reduced in the inner medulla but increased in the cortex and outer medulla, in the absence of any sign of toxicity. In conclusion, our in vitro and in vivo data indicate that demeclocycline mainly attenuates hyponatremia in SIADH by reducing adenylate cyclase 5/6 expression and, consequently, cAMP generation, AQP2 gene transcription, and AQP2 abundance in the renal inner medulla, coinciding with a reduced vasopressin escape response in other collecting duct segments.

Topics: Adenylyl Cyclases; Animals; Anti-Bacterial Agents; Aquaporin 2; Cells, Cultured; Cyclic AMP; Deamino Arginine Vasopressin; Demeclocycline; Disease Models, Animal; Hyponatremia; In Vitro Techniques; Inappropriate ADH Syndrome; Kidney Medulla; Male; Mice; Minocycline; Rats; Rats, Wistar; Vasopressins

Topics: Amitriptyline; Carbamazepine; Comorbidity; Demeclocycline; Diabetic Neuropathies; Diuretics; Furosemide; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Middle Aged; Saline Solution, Hypertonic; Spain; Urea; Vasopressins

Topics: Antidepressive Agents; Demeclocycline; Diuretics; Drinking Behavior; Humans; Hypernatremia; Hyponatremia; Practice Guidelines as Topic; Water Intoxication

We herein describe a rare case of hyponatremia that was aggravated by a burn injury. The patient was also found to have hypothyroidism, followed by SIADH, and finally CSWS, which showed complicated clinical features. A 68-year-old man was admitted for evaluation and treatment of a thermal burn. On admission, the patient was dehydrated, which was evidenced by physical signs. The patient had hyponatremia (serum Na 123 mmol/L) with high excretion of urinary sodium. Plasma AVP levels related to plasma osmolality were high. Plasma levels of renin and aldosterone were low, while the plasma ANP level was normal. However, there was no deficiency of mineralocorticoid or glucocorticoid. After admission, the hyponatremia worsened, and edema with hypoproteinemia developed. The patient was found to have hypothyroidism due to chronic thyroiditis. However, hyponatremia was not completely recovered with replacement of thyroid hormone. The hyponatremia was normalized by administration of DMC. The skin injury was treated with a skin graft. After DMC was discontinued, hyponatremia developed once again. However, this time, there was no inappropriate antidiuresis and the hyponatremia was normalized with the administration of fludrocortisone. These findings revealed that the hyponatremia in this patient may have been primarily due to CSWS. It was most likely exacerbated by hypothyroidism, burn injury, and SIADH caused by the infection. The patient showed physical signs of dehydration and edema. Furthermore, biochemical laboratory data were unable to distinguish between hypovolemia and non-hypovolemia. These complicated features were explained by multiple disorders

Topics: Aged; Anti-Bacterial Agents; Anti-Inflammatory Agents; Burns; Dehydration; Demeclocycline; Fludrocortisone; Humans; Hyponatremia; Hypothyroidism; Inappropriate ADH Syndrome; Male; Sodium

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anti-Bacterial Agents; Demeclocycline; Fatal Outcome; Humans; Hyponatremia; Male

To clarify the characteristics of vasopressin (AVP) secretion in patients with the syndrome of inappropriate antidiuresis (SIAD) related to central nervous system disorders, we examined the response of AVP secretion to osmotic stimulus by hypertonic saline infusion and analyzed the possible causative factors in six patients with SIAD associated with head trauma or cerebral infarction. Hyponatremia developed after head trauma in four patients and cerebral infarction in two patients. In all patients the clinical state and laboratory findings fulfilled the criteria for SIAD, which was supported by either nonsuppressible plasma AVP levels or effectiveness of treatments with water restriction, demeclocycline, nonpeptide V2 AVP antagonist or diphenylhydantoin. Although patterns of plasma AVP response to the osmotic stimulus varied, plasma AVP concentrations neither increased nor decreased to undetectable levels with a rise in plasma osmolality. In one patient, plasma AVP levels responded to increasing plasma osmolality when plasma osmolality normalized; in which the threshold and the sensitivity of osmostat were normal. In two other patients, AVP secretion responded to plasma osmolality after the treatment. The changes in AVP secretion were not due to nonosmotic stimuli for AVP release. In conclusion, this study shows that patients with SIAD and central nervous system disorders may have persistent AVP secretion with a loss of hypotonic suppression such as found in patients with adrenal insufficiency or depletional hyponatremia in central nervous system disorders, indicating that careful evaluation is necessary to determine the relationship between persistent AVP secretion and the pathogenesis of hyponatremic disorders.

Topics: Aged; Arginine Vasopressin; Cerebral Infarction; Craniocerebral Trauma; Demeclocycline; Female; Follow-Up Studies; Hormone Antagonists; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Middle Aged; Phenytoin; Saline Solution, Hypertonic; Water Deprivation; Water-Electrolyte Balance

Hyponatremia has been reported to occur in approximately 5% of carbamazepine-treated patients who otherwise do well on that agent. Demeclocycline has been used in the treatment of hyponatremia of various etiologies including one case of carbamazepine-induced hyponatremia.. We extended these observations by studying the effects of demeclocycline on carbamazepine-induced hyponatremia in six psychiatric inpatients.. Once serum sodium concentrations had normalized after carbamazepine discontinuation, demeclocycline prevented further decreases in sodium levels upon rechallenge with carbamazepine in five of six patients. Gender, smoking, and neurologic compromise may have played a role in the development of carbamazepine-induced hyponatremia as well as response to this strategy, although our sample size is too small to make firm conclusions.. Demeclocycline was successfully used in the prophylaxis of carbamazepine-induced hyponatremia and may be useful in cases that respond best to carbamazepine treatment.

Topics: Adult; Aged; Carbamazepine; Demeclocycline; Drug Therapy, Combination; Female; Hospitalization; Humans; Hyponatremia; Male; Mental Disorders; Middle Aged; Sodium

The authors describe a case of subarachnoid hemorrhage with hyponatremia accompanied by elevation of plasma atrial natriuretic peptide (ANP). The early phase of hyponatremia was classified as the syndrome of inappropriate secretion of antidiuretic hormone (ADH) due to subarachnoid hemorrhage. However, in the later phase, hyponatremia and natriuresis were accompanied by suppression of ADH while plasma ANP remained elevated. The patient was effectively treated with demeclocycline and hypertonic saline. The significance of ANP in the pathophysiology of increased natriuresis is discussed.

Topics: Aged; Atrial Natriuretic Factor; Demeclocycline; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Intracranial Aneurysm; Natriuresis; Saline Solution, Hypertonic; Subarachnoid Hemorrhage; Vasopressins

Topics: Demeclocycline; Humans; Hyponatremia; Mental Disorders; Water Intoxication

In most diabetic patients, the presence of hyponatremia is usually ascribed to severe hyperglycemia, hypertriglyceridemia, oral hypoglycemic agents, or other drugs. We describe two insulin-treated type II diabetic patients who were seen with severe rapid weight loss, hyponatremia, and diabetic amyotrophy despite good metabolic control. Laboratory evaluation of the hyponatremia suggested the syndrome of inappropriate antidiuretic hormone secretion. Their clinical presentations led to the suspicion of an underlying malignant neoplasm in each case. One patient required demeclocycline for treatment of his symptomatic hyponatremia, while the other improved with fluid restriction and intermittent furosemide therapy. The hyponatremia resolved spontaneously with improvement in body weight and the amyotrophy resolved after four to six months. After 24 to 36 months of close follow-up, no evidence of malignancy has been documented in either of the patients. We conclude that this clinical entity of amyotrophy is benign and should be included in the differential diagnosis of chronic hyponatremia in diabetic patients.

Topics: Atrophy; Body Weight; Demeclocycline; Diabetes Mellitus, Type 2; Electrolytes; Furosemide; Humans; Hyponatremia; Male; Middle Aged; Muscular Diseases; Sodium Chloride

Serum sodium concentration increased significantly in eight hyponatremic schizophrenic subjects treated with demeclocycline. The incidence of severe hyponatremic episodes was significantly reduced. The authors argue that mild impairments in urinary dilution contribute to water intoxication in most chronic psychotics who develop this syndrome. Demeclocycline may help these patients.

Topics: Adult; Chronic Disease; Compulsive Behavior; Demeclocycline; Drinking Behavior; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Middle Aged; Schizophrenia

8 cirrhotics with hyponatremia were given demeclocycline (DMC) 900 mg/day to investigate its effect on renal function, plasma renin activity, aldosterone and urinary excretion of prostaglandin E2 and kallikrein. In 7 patients DMC induced an increase of free water clearance (from -0.36 +/- 0.06 to 0.13 +/- 0.06 ml/min) and serum sodium concentration (from 125.4 +/- 0.09 to 131.1 +/- 1.0 mEq/l, mmol/l). In 5 of these patients DMC also induced a marked reduction of glomerular filtration rate (from 72.2 +/- 6.2 to 31,2 +/- 4.7 ml/min) and renal plasma flow (from 468 +/- 98 to 195 +/- 55 ml/min) which could not be explained on the basis of hypovolemia. In each case this renal impairment was not associated with changes in urinary concentration of beta 2-microglobulin, urinary casts excretion, fresh urine sediment or urine protein content and disappeared after discontinuation of the drug. DMC induced a marked increase in the urinary excretion of prostaglandin E2 (from 0.82 +/- 0.27 to 6.16 +/- 1.91 ng/min) in 6 out of the 7 patients who responded to DMC and a marked reduction in urinary kallikrein (from 16.1 +/- 4.4 to 4.2 +/- 1.6 pkat/min) in the 5 patients who developed renal insufficiency. The serum DMC concentration was greater than 5 micrograms/ml in all patients who responded to DMC, greater than 8 micrograms/ml in all cases who developed renal insufficiency and of 3 micrograms/ml in the case not responding to DMC. (ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Kidney Injury; Demeclocycline; Dinoprostone; Glomerular Filtration Rate; Humans; Hyponatremia; Kallikreins; Kidney; Liver Cirrhosis; Prostaglandins E; Renin-Angiotensin System

The syndrome of hyponatremia in psychiatric patients is described, and cases associated with psychotropic drug treatment are reviewed. The causative role of the drug should be documented by rechallenge or a water loading test. In some instances it is possible to continue psychotropic treatment by restricting fluids or administering demeclocycline.

Topics: Adult; Child; Demeclocycline; Humans; Hyponatremia; Inappropriate ADH Syndrome; Infant; Mental Disorders; Psychotropic Drugs

Two new observations of ISADH following head injury are described. A review of the medical literature is presented. Reports of ISADH after head injury are rare in comparison to the frequent occurrence of hydroelectrolytic disorders in the same situation. Attention is drawn to misleading clinical pictures, suggestive of neurosurgical conditions. Intracranial hematoma is frequently associated with ISADH and should be looked for in patients who fail to respond to therapy.

Topics: Aged; Craniocerebral Trauma; Demeclocycline; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male

Demeclocycline, a competitive inhibitor of antidiuretic hormone at renal tubules, was studied in a patient with the syndrome of psychosis, psychogenic polydipsia, and episodic water intoxication. Under double-blind, placebo-controlled conditions, demeclocycline substantially reduced the severity and frequency of hyponatremic episodes.

Topics: Adult; Demeclocycline; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Schizophrenia; Schizophrenic Psychology; Water Intoxication

Topics: Demeclocycline; Humans; Hyponatremia; Water

Topics: Bronchopneumonia; Cardiomyopathies; Child; Child, Preschool; Demeclocycline; Diuretics; Female; Humans; Hypokalemia; Hyponatremia; Inappropriate ADH Syndrome; Respiratory Insufficiency

Seventeen patients with cancer or aplastic anemia received demeclocycline as treatment for hyponatremia. Prior to demeclocycline therapy no patients showed clinical signs of fluid overload or saline depletion. In all patients inappropriately concentrated urine (mean urine osmolality = 548 mOSM/kg H2O) or increased urine content of sodium (mean urine sodium = 91 mEq/L) were documented prior to demeclocycline therapy. No patient had developed hyponatremia in association with antineoplastic drug therapy. The average serum sodium (NaS) at the time of initiation of therapy was 121 mEq/L. NaS increased in all patients despite the simultaneous administration of generous volumes of fluid. NaS exceeded 130 mEq/L and average of 3.5 days following institution of demeclocycline. Patients lost an average of 2.3 kg during demeclocycline. The toxicity noted following demeclocycline was azotemia and increased serum creatinine. Eight patients developed serum urea nitrogen (SUN) in excess of 25 mg/dl; average maximum creatinine in these eight patients was 1.9 mg/dl. Average peak creatinine in eight patients who did not develop azotemia was 0.87 mg/dl. Azotemia seemed to be correlated with simultaneous administration of other nephrotoxic agents and with administration of higher doses (1200 mg/day) of demeclocycline.

Topics: Creatinine; Demeclocycline; Humans; Hyponatremia; Neoplasms; Osmolar Concentration; Uremia; Water Intoxication

In five hyponatremic, cirrhotic patients, demeclocycline hydrochloride was used to inhibit the hydroosmotic effect of vasopressin. In four, renal impairment developed during the 7 to 20 days of demeclocycline hydrochloride (900 to 1,200 mg/day) administration. In these four patients, creatinine clearance fell (72 to 20 mL/min, P less than .01) as BUN (12 to 47 mg/dl, P less than .02) and serum creatinine (0.9 to 4.2 mg/dl, P less than .01) levels rose. The azotemic effect of the drug could not be accounted for consistently by volume depletion secondary to its natriuretic effect. However, a close correlation between plasma demeclocycline levels and its azotemic effect was observed. We conclude that a nephrotoxic effect of demeclocycline severly limits its usefulness in treating hyponatremia in the cirrhotic patient.

Topics: Adult; Creatinine; Demeclocycline; Glomerular Filtration Rate; Humans; Hyponatremia; Kidney; Kidney Diseases; Liver Cirrhosis, Alcoholic; Male; Natriuresis; Vasopressins

Topics: Demeclocycline; Glomerular Filtration Rate; Humans; Hyponatremia; Kidney; Kidney Diseases; Natriuresis

Topics: Demeclocycline; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Lung Neoplasms; Middle Aged

Topics: Demeclocycline; Female; Humans; Hyponatremia; Hypothyroidism; Inappropriate ADH Syndrome; Middle Aged; Vasopressins; Water-Electrolyte Imbalance

Known physiologic mechanisms explain the elevated blood ADH levels observed in most patients with the syndrome of inappropriate ADH. Therefore the word "inappropriate" is a misnomer. It implies that the mechanisms that regulate ADH release are not functioning normally--which is not true. The term misleads the physician who, ideally, should determine why a patient has an excessive blood ADH level and initiate appropriate treatment. Patients with ectopic production of ADH and hyponatremia should be so labeled: "Hyponatremia due to ectopic ADH production." The term SIADH, if used at all, should be reserved for the rare patient with CNS injury or disease that causes increased ADH release and in which the hypothalamic center does not respond normally to afferent peripheral stimuli.

Topics: Blood; Demeclocycline; Furosemide; Humans; Hyponatremia; Inappropriate ADH Syndrome; Lithium; Osmolar Concentration; Pressoreceptors; Saline Solution, Hypertonic; Vasopressins

Topics: Demeclocycline; Heart Failure; Hyponatremia; Inappropriate ADH Syndrome; Lung Neoplasms; Respiratory Tract Infections; Water Deprivation

Topics: Aged; Demeclocycline; Humans; Hyponatremia; Liver Cirrhosis, Alcoholic; Male; Porphyrias

Topics: Ascites; Demeclocycline; Edema; Humans; Hyponatremia; Osmolar Concentration; Vasopressins; Water Intoxication

Topics: Demeclocycline; Glucose; Heart Failure; Humans; Hyponatremia; Insulin; Potassium

We evaluated demeclocycline and lithium therapy in 10 patients with the syndrome of inappropriate secretion of antidiuretic hormone. Despite severe water restriction, all patients had hyponatremia (mean +/- S.E.M. serum sodium of 122 +/- 1.1 meq per liter) and elevated urine osmolality (744 +/- 59 mOsm per kilogram) before treatment. Demeclocycline (600 to 1200 mg daily) restored serum sodium concentration to 139 +/- 1.1 meq per liter within five to 14 days, permitting unrestricted water intake in all patients. In three patients given lithium carbonate (900 mg daily) the serum sodium concentration, urine osmolality and urine volume were unchanged; since two patients had adverse central-nervous-system symptoms during lithium therapy, further study of this agent was abandoned. A patient with an unusual 22-year history of the syndrome was unresponsive to lithium, whereas long-term treatment with demeclocyline was markedly effective. Demeclocycline is superior to lithium in the treatment of the syndrome and may obviate the need for severe water restriction.

Topics: Adult; Aged; Child; Chronic Disease; Demeclocycline; Drug Evaluation; Female; Humans; Hyponatremia; Lithium; Male; Middle Aged; Osmolar Concentration; Sodium; Syndrome; Vasopressins

Topics: Demeclocycline; Humans; Hyponatremia; Lithium; Osmolar Concentration; Syndrome; Vasopressins

A hypothyroid, 72-year-old woman with idiopathic hypopituitarism manifested severe hyponatremia, plasma hypoosmolality, and inappropriately elevated urine osmolality suggestive of a syndrome of inappropriate antidiuretic hormone secretions. The hyponatremia did not respond to demeclocycline hydrochloride, and antidiuretic hormone (ADH) levels measured by a specific radioimmunoassay were appropriately suppressed. Subsequent replacement therapy with levothyroxine sodium resulted in correction of the hyponatremia. Thus, both direct assay as well as hormone blockade failed to show an action of ADH in mediating the water retention.

Topics: Aged; Demeclocycline; Female; Humans; Hyponatremia; Hypopituitarism; Hypothyroidism; Sodium; Thyroxine; Vasopressins

The efficacy of demeclocycline hydrochloride in suppressing the tubular action of tumoral antidiuretic products was tested in seven patients with the syndrome of inappropriate antidiuretic hormone secretion. In all patients, demeclocycline hydrochloride (1,200 mg/day) induced production of hypotonic urine and corrected hyponatremia despite large fluid intakes. Comparison of the response to a standard water load before and during treatment showed a notable improvement in the response to water ingestion. Even though demeclocycline moderately impairs renal function, it appears to be the treatment of choice in the chronic form of the syndrome.

Topics: Administration, Oral; Aged; Carcinoma, Small Cell; Chronic Disease; Demeclocycline; Depression, Chemical; Dose-Response Relationship, Drug; Humans; Hyponatremia; Kidney Concentrating Ability; Lung Neoplasms; Male; Middle Aged; Syndrome; Vasopressins

Topics: Carcinoma, Small Cell; Demeclocycline; Humans; Hyponatremia; Lung Neoplasms; Male; Middle Aged; Paraneoplastic Endocrine Syndromes; Phosphorus; Uric Acid; Vasopressins

Topics: Demeclocycline; Humans; Hyponatremia; Male; Middle Aged

Topics: Demeclocycline; Humans; Hyponatremia; Male; Middle Aged; Osmolar Concentration; Syndrome; Vasopressins

Topics: Ascites; Demeclocycline; Humans; Hyponatremia; Kidney; Liver Cirrhosis

Topics: Demeclocycline; Hormones, Ectopic; Humans; Hyponatremia; Male; Middle Aged; Paraneoplastic Endocrine Syndromes; Tracheal Neoplasms; Vasopressins

Topics: Ascites; Demeclocycline; Humans; Hyponatremia; Liver Cirrhosis; Natriuresis; Water-Electrolyte Imbalance

Topics: Carcinoma, Small Cell; Demeclocycline; Diuresis; Humans; Hyponatremia; Lung Neoplasms; Male; Middle Aged; Syndrome; Vasopressins

We have studied the effects of demeclocycline on the water metabolism of a patient with the syndrome of inappropriate antidiuretic hormone (ADH) secretion who presented with a serum sodium concentration of 110 meq/litre. Free water clearance was studied before, during, and after treatment with demeclocycline. This study shows that demeclocycline (900 mg/day) can at least partially inhibit the action of ADH in the setting of tumor-induced ADH secretion, with the production of a reversible, partial nephrogenic diabetes insipidus, and with few or no side effects. Demeclocycline may be useful in the treatment of chronic inappropriate ADH secretion.

Topics: Carcinoma, Small Cell; Demeclocycline; Diabetes Insipidus; Humans; Hyponatremia; Kidney Diseases; Lung Neoplasms; Male; Middle Aged; Osmolar Concentration; Syndrome; Urine; Vasopressins