Hyponatraemia associated with psychotropic medications. A review of the literature and spontaneous reports

Psychotropic medication-induced hyponatraemia is an uncommon but important clinical problem with potential serious consequences if not recognised and treated early. Several risk factors have been associated with the development of hyponatraemia. This article reviews reported cases of hyponatraemia associated with the use of psychotropic medications and evaluates possible risk factors and causes. The data were sourced by a search of Medline for reports of hyponatraemia associated with the use of psychotropic medication between January 1966 and December 2000 and a search of US Food and Drug Administration (FDA) spontaneous reporting system database between January 1966 and December 1999. All the reports were included in this review. In the case reports the following data were assessed: age, gender, daily dosage, days to onset, days to recovery, medical condition, concurrent medications. Several risk factors were identified: advanced age, female gender, use of other medications, medical comorbidity. The risk of hyponatraemia was found to be higher during the first 2 weeks of treatment. Administration of the dosage of the drug was not found to be related to the development of hyponatraemia. Hyponatraemia can cause confusion, agitation and lethargy. Any change in the course of illness should alert the physician to the possibility of hyponatraemia.     

Antitumour property and toxicity of Barringtonia racemosa Roxb seed extract in mice

Ethnomedical survey has shown that the seeds of Barringtonia racemosa Roxb are traditionally used in certain remote villages of Kerala (India) to treat cancer like diseases. So the seed extracts were tested for their antitumour activity and toxicity. Intraperitoneal (i.p.) daily administration of 50% methanol extract of this seed to mice challenged with 1 million Dalton's Lymphoma Ascitic (DLA) cells resulted in remarkable dose dependent anti-DLA activity in mice. The optimum dose was found to be 6 mg/kg. This dose protected all the animals challenged with the tumour cells. The efficacy of the drug was found to be better than that of a standard drug, vincristine in this tumour model. However, the oral administration showed only marginal activity compared to i.p. administration. The extract was found to be devoid of conspicuous acute and short-term toxicity to mice, when administered daily, (i.p.) for 14 days up to a dose of 12 mg/kg (which was double the concentration of optimum therapeutic dose). The treated mice showed conspicuous toxic symptoms only at 24 mg/kg. The LD(50) to male mice for a single i.p. dose was found to be 36 mg/kg. The seed extract is an attractive material for further studies leading to drug development.     

Managing bipolar disorder in the elderly: defining the role of the newer agents

Clinical research in geriatric psychopharmacology has been a relatively neglected focus compared with the wealth of information on younger populations, and there is a dearth of published, controlled trials. Similarly, these are limited data in the area of geriatric bipolar disorder. Although there is an absence of rigorous, evidence-based information, preliminary data on older adults with bipolar disorder suggest some promising treatment options and important differences in older versus younger patients with bipolar illness. Lithium, while widely utilised in younger populations, is often poorly tolerated in the elderly. Clinical evidence regarding use of antiepileptic compounds in late-life bipolar disorder is generally compiled from bipolar disorder studies in mixed populations, studies in older adults with seizure disorders, and studies on dementia and psychotic conditions other than bipolar disorder. Valproate semisodium and carbamazepine are widely prescribed compounds in older adults with bipolar disorder. However, the popularity of these compounds has occurred in context of an absence of evidence-based data. The atypical antipsychotics have expanded the treatment armamentarium for bipolar disorder in mixed populations and may offer particular promise in management of bipolar illness in older populations as well. Olanzapine, risperidone, quetiapine, ziprasidone and aripiprazole are atypical antipsychotics that have been approved by the US FDA for the treatment of bipolar disorder; however, there are no published, controlled trials with atypical antipsychotics specific to mania in geriatric patients. Preliminary reports on the use of clozapine, risperidone, olanzapine and quetiapine suggest a role for the use of these agents in late-life bipolar disorder. Information with ziprasidone and aripiprazole specific to geriatric bipolar disorder is still lacking.     

Reduction of phosphoinositides and diacylglycerol levels in repeatedly dibutyltin-dilaurate-treated rat brain.

Oral administration of a single dose of dibutyltin dilaurate (DBTL, 80 mg/kg body wt.), 2 or 24 h after treatment, caused no significant change in the levels of diacylglycerol and phosphoinositides in rat cerebrum (forebrain), whereas daily administration of DBTL (40 or 80 mg/kg body wt.) for 3 days (24 h after the final treatment) decreased the levels of diacylglycerol and phosphoinositides (phosphatidylinositol, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate) in a concentration-dependent manner without influencing the levels of phosphatidylcholine in rat cerebrum. These studies indicate impairment of the phosphoinositide messenger system in rat cerebrum following repeated exposure to DBTL.     

Anticoagulation‐related nephropathy

Anticoagulation‐related nephropathy (ARN) is a significant but underdiagnosed complication of anticoagulation that is associated with increased renal morbidity and all‐cause mortality. Originally described in patients receiving supratherapeutic doses of warfarin who had a distinct pattern of glomerular hemorrhage on kidney biopsy, ARN is currently defined as acute kidney injury (AKI) without obvious etiology in the setting of an International Normalized Ratio (INR) of > 3.0. The underlying molecular mechanism is thought to be warfarin‐induced thrombin depletion; however, newer studies have hinted at an alternative mechanism involving reductions in activated protein C and endothelial protein C receptor signaling. Prompt recognition of ARN is critical, as it is associated with accelerated progression of chronic kidney disease, and significant increases in short‐term and long‐term all‐cause mortality. Prior investigations into ARN have almost universally focused on anticoagulation with warfarin; however, recent case reports and animal studies suggest that it can also occur in patients taking novel oral anticoagulants. Differences in the incidence and severity of ARN between patients taking warfarin and those taking novel oral anticoagulants are unknown; a post hoc analysis of routinely reported adverse renal outcomes in clinical trials comparing warfarin and novel oral anticoagulants found no significant difference in the rates of AKI, a prerequisite for ARN. Given the significant impact of ARN on renal function and all‐cause mortality, a thorough understanding of the pathophysiology, molecular mechanisms, clinical spectrum and therapeutic interventions for ARN is crucial to balance the risks and benefits of anticoagulation and optimize treatment.