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Biomedical subjects

N R Cutler

Publications and source records attributed to N R Cutler.

At least 145 records · Page 8Linked to original sources

Implications of dosing tricyclic antidepressants and benzodiazepines in geriatrics.

It is important to understand both the kinetic and the dynamic implications of dosing TCAs and BZs in the elderly, for whom these drugs are frequently prescribed. The TCAs are used to treat responsive signs and symptoms including such somatic complaints as chest pain, dizziness, and arthralgias, as well as the endogenous signs such as loss of appetite with associated weight loss, psychomotor retardation, loss of libido, and insomnia. The pharmacokinetic studies of TCAs such as desipramine and nortriptyline have shown few, if any, age-related changes. The dose required for responsivity is significantly reduced for both TCAs (desipramine and nortriptyline) in the elderly, which may suggest increased end-organ responsiveness. The major recommendations for treatment of depression with nortriptyline in the elderly are (1) to administer small doses in order to avoid side effects, and (2) to expect a longer response time for the antidepressant effect than in young and middle-aged depressed patients. Although the BZs are extensively prescribed in the elderly, primarily for insomnia and anxiety, the physiologic and biochemical changes of aging alter the kinetics and dynamics of these extensively metabolized and slowly eliminated drugs. Based on the kinetic data and information in Tables 1 and 2, the relatively sensitive elderly population should receive a reduced dosage. Careful evaluation of the patient and the kinetic profile of the agent employed will ensure safe use of these drugs. A clear understanding of anxiety and respect for the alterations in the pharmacokinetics and pharmacodynamics of these agents in the elderly will allow the physician to prescribe the BZs wisely. As with the TCAs, remember to administer doses of BZs that are reduced by 50 to 75 per cent of the usual recommended doses for young and middle-aged individuals and to increase dosage in small increments. Ultimately, sound, scientifically based, clinical judgment that considers the needs of the patient is the best guide for the selection of an appropriate BZ.

Adipose Tissue↗

Effects of chronic desipramine on plasma norepinephrine concentrations and cardiovascular parameters in elderly depressed women: a preliminary report.

The effect of chronic administration of desipramine, a relatively specific inhibitor of the reuptake of norepinephrine (NE), on heart rate, blood pressure, and concentrations of NE in plasma was examined in elderly depressed women. Plasma NE concentrations rose significantly following administration of desipramine, while there was no significant change in either heart rate or blood pressure. Implications of these findings are discussed with relationship to the selection of appropriate types and doses of antidepressants in the elderly.

Aged↗

Down's syndrome in adults: brain metabolism.

The cerebral metabolic rate for glucose, as measured with positron emission tomography and fluorine-18-labeled 2-deoxy-D-glucose, was significantly higher in four healthy young subjects with trisomy 21 syndrome (Down's syndrome) than the mean rate in healthy young controls. The rate of cerebral glucose utilization in the frontal lobe of a 51-year-old subject with Down's syndrome was significantly lower than the rate in the young subjects with this syndrome, but approximated the rate in middle-aged controls. Thus glucose utilization by the brain appears to be excessive in young adults with Down's syndrome but may decline with age in some brain regions.

Adult↗

Apomorphine response and subtyping of schizophrenia.

(1) We conducted a double-blind study of acute effects of low-dose apomorphine (0.01 mg/kg) in 12 chronic schizophrenic patients. (2) Overall, there was no significant difference in therapeutic response to apomorphine versus placebo. (3) Of the individual subscales of the Brief Psychiatric Rating Scale, anxiety and depression syndromes showed significant improvement with apomorphine. (4) On dividing the schizophrenic patients into two groups on the basis of computed tomography (CT) scans, it was found that there was a significant difference in their responsiveness to apomorphine. (5) Patients with abnormal CT scans (primarily, large ventricles) tended to have improvement or no change with apomorphine, whereas those with normal CT scans tended to have worsening of symptoms. (6) Possible implications of our findings are discussed.

Adult↗

Assessing the noradrenergic system in normal aging: a review of methodology.

Studies evaluating plasma norepinephrine in the normal elderly have found significant increases as compared to the young and middle-aged individuals. The increased plasma norepinephrine concentrations found during the normal aging process in man may be relevant to both the understanding of drug therapeutics and underlying mechanisms of the noradrenergic system in the elderly. The authors critically review the experimental design of studies that have evaluated plasma norepinephrine and age. The various conditions and methods for assessment of plasma norepinephrine concentrations, which may contribute to the finding of a hypernoradrenergic system in the aged, are examined. An attempt is made to collate the studies and develop a standardized methodology for studying the peripheral noradrenergic system in the elderly.

Adult↗

Low-dose apomorphine reduces serum homovanillic acid concentrations in schizophrenic patients.

This study was carried out to evaluate the postulated dopaminergic auto-receptor regulatory effect in man of low-dose apomorphine. Behavior and serum homovanillic acid concentrations following low-dose apomorphine were investigated. Five medicated chronic schizophrenic patients had serum homovanillic acid concentrations measured by mass fragmentography before and after 0.005 mg/kg of apomorphine or saline placebo. Results demonstrate significant reductions in serum homovanillic acid concentrations in all five subjects following apomorphine as compared with placebo. These findings present direct evidence of a specific dopamine autoreceptor effect of low-dose apomorphine in schizophrenic patients.

Adult↗

Altered hydroxydesipramine concentrations in elderly depressed patients.

Recent reports demonstrate that hydroxy metabolites of desipramine (DMI) have pharmacologic activity and do not just produce side effects. In patients treated with DMI, we determined the ratio of 2-hydroxydesipramine (2-OH-DMI) to drug at steady state. The ratios in the elderly patients were higher than in younger patients, and whereas plasma levels of 2-OH-DMI increased with age, urinary clearances decreased. The known decrease in glomerular filtration with age may explain the selective increase of 2-OH-DMI concentration in the elderly.

Adult↗

State-related cyclical dyskinesias in manic-depressive illness.

Cyclical dyskinesias in two rapidly cycling manic-depressive patients recurred during depression and disappeared during mania. One case is reviewed in detail including findings of a 2-year follow-up. Spinal fluid biochemical data are presented and discussed. The finding of a reversible neurological alteration associated with changes in clinical state is of interest in relationship to the mechanisms underlying tardive dyskinesia and also provides evidence of a biological dysfunction in manic-depressive illness.

Adult↗

Concentrations of desipramine in elderly women.

Seven elderly depressed women were given desipramine, and plasma concentrations of the drug were measured from blood samples drawn after a single dose and during long-term use. The concentrations were no different from those found in younger patients. Aging does not seem to alter the plasma concentration of desipramine, and the authors conclude that the increased incidence and severity of the drug's side effects are probably not due to high drug concentrations.

Aged↗

The tricyclic antidepressants.

Because only 9.4% of depressions are recognized at initial evaluation by primary physicians, the diagnosis of depression is important. Forty percent of a group of mixed depressions will resolve in a month without treatment, and 70% will resolve with the use of tricyclic antidepressants. Research on plasma levels of tricyclic antidepressants suggest new clinical strategies for adjusting dosages; neurochemical studies may provide an appropriate selection process for choosing a tricyclic antidepressant.

Antidepressive Agents, Tricyclic↗