lithium-chloride and Hyponatremia

Carbamazepine (Carba) is an anticonvulsant and psychotropic drug used widely for the treatment of intellectual disability and severe pains, but the incidence of hyponatremia is a common related occurrence. This hyponatremia is frequently attributed to a SIADH induced by this drug. It is also known that Carba is used to decrease the urinary volume in Diabetes Insipidus (DI) because it has an antidiuretic effect. Lithium (Li) is one of the most important drugs used to treat bipolar mood disorders. However Li has the undesirable capacity to induce DI. Nowadays, the association of these drugs is used in the treatment of patients with psychiatric and neurological problems.. In vivo and in vitro (microperfusion) experiments were developed to investigate the effect of Carba in the rat Inner Medullary Collecting Duct (IMCD).. The results revealed that Carba was able to stimulate the V2 vasopressin receptor-Protein G complex increasing the (Pf) and water absorption. In vivo studies showed that in rats with lithium-induced DI, Carba decreased the urinary volume and increased the urinary osmolality. AQP2 expression was increased both in normal IMCD incubated with Carba and in IMCD from lithium-induced DI after Carba addition to the diet, when compared with the control.. These results showed that the hyponatremia observed in patients using this anticonvulsant drug, at least in part, is due to the Carba capacity to increase IMCD's Pf and that the Lithium-Carbamazepine association is beneficial to the patient.

Topics: Absorption; Animals; Anticonvulsants; Aquaporin 2; Carbamazepine; Diabetes Insipidus; Disease Models, Animal; Hyponatremia; Kidney Tubules, Collecting; Lithium Chloride; Male; Rats; Rats, Wistar; Receptors, Vasopressin; Water

Although, pharmacological intervention with a selective arginine vasopressin (AVP) V(2) receptor antagonist has been demonstrated to be effective for syndrome of inappropriate secretion of antidiuretic hormone (SIADH), its long-term administration has some therapeutic limitations. Lithium, a drug for bipolar disorders, has been known to cause nephrogenic diabetes insipidus by reducing kidney-specific apical water channel, aquaporin 2 (AQP2) expression in the collecting ducts. However, its pharmacological efficacy for SIADH still remains to be elucidated.. Hyponatraemia was induced in male Sprague-Dawley rats by water loading and subcutaneous infusion of 1-deamino-8-D-arginine vasopressin. For the treatment, lithium chloride (LiCl) was administered singly or in combination with OPC-31260 and/or furosemide for 7 days. Protein expression of AQP2 was examined by western blotting at the end of the observation period.. The LiCl administration elevated serum sodium levels in a dose-dependent manner. The therapeutic effect started 3 days after the initial administration and gradually increased. Western blot analysis at the end of the treatment demonstrated dose-dependent reduction of AQP2 protein expression. Additional administration of LiCl (100 mg/kg/day, the dose demonstrated to maintain serum lithium concentration within therapeutic range) to low dose OPC-31260 maintained well the initial elevation of serum sodium level during the treatment. Western blot analysis after combination therapy demonstrated the absence of re-increase in AQP2 expression noted at the end of OPC-31260 treatment. However, further additive effect could not be obtained even when both LiCl and furosemide were added together to low dose OPC-31260.. Although the single effect of therapeutic dose of lithium was weak, it effectively and safely compensated for the therapeutic limitations of a low dose of AVP V(2) receptor antagonist for SIADH by reducing AQP2 expression.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Aquaporin 2; Benzazepines; Diabetes Insipidus, Nephrogenic; Disease Models, Animal; Drug Synergism; Furosemide; Hyponatremia; Inappropriate ADH Syndrome; Kidney Tubules, Collecting; Lithium Chloride; Male; Rats; Rats, Sprague-Dawley; Receptors, Vasopressin

1. This study compared the effects of the antimanic drugs, lithium and valproic acid, on GABA and glutamine CSF concentration and on head-shakes during hyponatremia. 2. Hyponatremic and normonatremic rats were treated with 2 mEq/kg lithium and 360 mg/kg valproic acid. Behavioral observation was conducted for 120 min after which blood and CSF collection were performed under anesthesia. 3. Peritoneal dialysis with glucose induced moderate hyponatremia and doubled glutamine CSF concentrations. Both lithium and valproic acid significantly increased GABA CSF levels in normonatremic and hyponatremic animals. Valproic acid induced head-shakes and increased CSF glutamine concentration. 4. The results suggest that both antimanic drugs have similar effects on GABA, but lithium is preferred if the increase in glutamine concentration poses a problem, either in the presence or absence of hyponatremia.

Topics: Animals; Antimanic Agents; Female; gamma-Aminobutyric Acid; Glutamine; Hyponatremia; Lithium Chloride; Rats; Rats, Wistar; Valproic Acid

Topics: Adult; Antimanic Agents; Bipolar Disorder; Diet, Reducing; Female; Humans; Hyponatremia; Lithium Chloride

Previous studies have shown that many treatments that stimulate the peripheral secretion of oxytocin (OT) and vasopressin (AVP) from the pituitary simultaneously increase the levels of these peptides in the cerebrospinal fluid (CSF). Since osmotically and nonosmotically stimulated pituitary secretion of OT and AVP is markedly blunted in hyponatremic rats, the present studies evaluated whether central OT and AVP secretion into the CSF is similarly inhibited during sustained hyponatremia. Adult male rats with indwelling cisterna magna cannulae were rendered hyponatremic (plasma [Na+] < 110 mmol/l) by s.c. infusion of desmopressin (dDAVP; 10 ng/h) in combination with ingestion of a liquid diet for 3 days, then subjected to osmotic (i.v. or i.p. injection of 2 M NaCl; HS) or nonosmotic (6 mmol/kg of 0.15 M LiCl i.p.) stimulation. In normonatremic rats both i.v. and i.p. HS caused marked increases in plasma OT and AVP levels 30 min after treatment. Significant elevations of OT, but not AVP, were also present in CSF. Despite similar increases in plasma Na+ concentrations, plasma OT responses in the hyponatremic rats were absent after HS i.v. and were significantly blunted after HS i.p., but neither group had increased plasma AVP. In parallel with the plasma results, CSF OT responses were absent in hyponatremic rats given HS i.v. and significantly blunted in hyponatremic rats given HS i.p., but neither group had increased CSF AVP. Nonosmotic stimulation with isotonic LiCl increased OT levels both in plasma and CSF in normonatremic rats 20 min after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arginine Vasopressin; Brain; Chronic Disease; Hyponatremia; Injections, Intraperitoneal; Injections, Intravenous; Isotonic Solutions; Lithium Chloride; Male; Oxytocin; Rats; Rats, Sprague-Dawley; Reference Values; Saline Solution, Hypertonic