Investigation of neurokinin-2 and -3 receptors in the human and pig bladder.

OBJECTIVE: To investigate the role of neurokinin (NK)-2 and -3 receptors in mediating the contraction of detrusor muscle strips from human and pig, to determine whether the pig is a good model for the study of tachykinin receptors in the human bladder, as the biological actions of tachykinins, e.g. substance P and NKA are mediated via three distinct receptor subtypes, NK-1, -2 and -3. MATERIALS AND METHODS: Strips of detrusor muscle were obtained from the bladder dome and neck of female pigs and from patients undergoing cystectomy. Cumulative concentration-response curves to NKA were obtained in the absence and presence of either the NK-2 receptor-selective antagonist SR48968 or the NK-3 receptor-selective antagonist SB223412. RESULTS: NKA produced concentration-dependent contractions in the human and pig detrusor muscle; the curves were shifted to the right by SR48968, with high affinity (pKB 8.9, 8.3 and 8.0 in the human, pig dome and pig neck, respectively), whereas SB223412 had a minimal effect (pKB 5.8, 5.8 and 6.3, respectively). CONCLUSION: These data confirm that the NK-2 receptor subtype mediates NKA-induced contraction of the human and pig detrusor muscle. The NK-3 receptor appears to have no role in detrusor contraction of either species. The results also provide evidence that the NK-2 receptor in human and pig are the same, and the latter may be an appropriate species to study tachykinin-induced contractions in human bladder.

Treatment of depression in late life.

Depression is a common problem in older patients and a significant contributor to morbidity and mortality in this population. The identification and treatment of depression is more complex in older patients because of difficulty in diagnosis, coexisting illnesses, and concurrent drug therapy. In addition, a variety of medical conditions and drugs can cause depression. Treatment often has to be modified in consideration of other illnesses, medications, and the reduced ability of the elderly to metabolize drugs. Duration of treatment may be longer than with young patients because older adults may respond more slowly to antidepressants.

Update on the use of antidepressants in the elderly.

This chapter presents a review of the current status of depression treatment for the elderly. The authors describe currently available antidepressants and discuss special considerations when they are used to treat elderly patients.

Drug-induced seizures in the elderly. Causative agents and optimal management.

We conducted a review of drugs that were most commonly associated with inducing seizures in the elderly population. The method for determining the risk of these agents includes evaluating the utilisation and the percentage of adverse events in previous studies and case reports. Classes of medications, such as anti-psychotics and antidepressants, are extensively reviewed to provide the clinician with treatment options in high risk patients. The risk of seizures secondary to the withdrawal of alcohol (ethanol) and benzodiazepines, and methods employed to minimise the risk are discussed. In addition, the management of patients with drug-induced seizures is delineated. Drug-induced seizures are a potentially serious adverse effect. It is important that clinicians are aware of which classes of medications and individual medications are associated with reducing seizure threshold.

ECT and tardive dyskinesia.

Three cases of elderly depressed patients with symptoms of tardive dyskinesia (TD) subsequently treated with electroconvulsive therapy (ECT) are presented. These cases are discussed in relation to several cases reported in the literature of ECT and TD. The possibility of improvement in symptoms of TD in certain patients is discussed.