piperidines and Inappropriate-ADH-Syndrome

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Aquaporin 2; Arginine Vasopressin; Benzazepines; Diabetes Insipidus; Diabetes Insipidus, Nephrogenic; Drug Design; Humans; Hyponatremia; Inappropriate ADH Syndrome; Mutation; Piperidines; Quinolones; Receptors, Vasopressin

Vasopressin, or antidiuretic hormone, is a peptide hormone that is released from the posterior pituitary gland in response to changes in blood pressure and plasma osmolality. The main pathophysiological states associated with high plasma vasopressin concentrations are cirrhosis, cardiac failure and syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Pharmacological treatments for disorders of excess vasopressin secretion have been limited. However, oral bio-available selective and non-selective V(1) and V(2) receptor antagonists have recently become available for clinical use. Water retention in cirrhosis is a common problem, leading to ascites, peripheral oedema and hyponatraemia. Raised plasma vasopressin concentrations and decreased delivery of glomerular filtrate are believed to be the most important factors in the development of water retention. V(2) receptor antagonists are aquaretic agents that promote water excretion and improve hyponatraemia. Their potential role in cirrhosis has been examined in a number of recent studies that have shown increased free water clearance and serum sodium concentrations with few adverse effects. V(2) receptor antagonists represent a novel and promising new class of agent that may have major clinical utility in the treatment of patients with liver cirrhosis.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Azepines; Benzamides; Benzazepines; Controlled Clinical Trials as Topic; Diuretics; Heart Failure; Homeostasis; Humans; Inappropriate ADH Syndrome; Liver Cirrhosis; Models, Animal; Morpholines; Piperidines; Pyrroles; Quinolones; Rats; Spiro Compounds; Vasopressins

Topics: Animals; Benzazepines; Cells, Cultured; Hyponatremia; Inappropriate ADH Syndrome; Kidney Tubules, Collecting; Muscle, Smooth, Vascular; Piperidines; Quinolones; Rats; Rats, Brattleboro; Rats, Sprague-Dawley; Vasopressins

The effects of lorcainide, a new antiarrhythmic drug, on serum electrolytes and osmolality are described in a series of 33 patients with organic heart disease and complex ventricular arrhythmias treated with lorcainide. In eight patients, a mean decrease in serum Na+ of 8.25 +/- 3.2 mEq/L was observed after a single 200 mg intravenous dose of lorcainide. Sixteen of 33 patients developed significant hyponatremia and hypoosmolality during oral treatment with lorcainide. In all except two patients, serum Na+ returned to normal values within 3 to 12 months of continued lorcainide therapy. Low serum Na+ and hypoosmolality in the absence of volume depletion, clinically manifest edema, and unaltered renal, adrenal, cardiac, or thyroid function suggest that this antiarrhythmic drug produced the syndrome of inappropriate antidiuretic hormone secretion (SIADH). SIADH appeared to be transient and asymptomatic in our patients. One patient developed severe hyponatremia with serum Na+ of 108 mEq/L when hydrochlorothiazide was given to control hypertension. It is concluded that SIADH is an important side effect of lorcainide therapy. We recommend that serum Na+ be carefully monitored in patients started on lorcainide therapy, and extreme caution should be exercised in prescribing diuretics to patients with persistent hyponatremia.

Topics: Adult; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzeneacetamides; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Middle Aged; Piperidines; Potassium; Sodium; Vasopressins