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Biomedical subjects

B G Wells

Publications and source records attributed to B G Wells.

34 records · Page 2Linked to original sources

Characterizing anticholinergic abuse in community mental health.

To identify factors associated with anticholinergic abuse in patients taking antipsychotics and anticholinergics and to document the extent of extrapyramidal side effects in anticholinergic abusers, 21 anticholinergic abusers were matched with 21 controls without a history of anticholinergic abuse for diagnosis and antipsychotic dose. Data were collected prospectively, and extrapyramidal side effects and abnormal involuntary movements were evaluated using the Modified Simpson Angus Scale and the Abnormal Involuntary Movement Scale. The abuse group reported significantly more subjective effects from anticholinergic agents than did those in the control group (mean +/- SD = 10.5 +/- 5.4 vs. 6.5 +/- 3.7, p less than 0.05). The abuse group was significantly more likely to report feeling a buzz (p less than 0.05) and difficulty learning (p less than 0.05) when taking anticholinergic medications. Abusers reported abusing significantly more drugs in the past (2.7 +/- 2.1 vs. 0.8 +/- 0.9, p less than 0.01) and had taken antipsychotics (12.7 +/- 6.3 vs. 8.7 +/- 5.4 years, p less than 0.05) and anticholinergics (10.9 +/- 3.1 vs. 6.1 +/- 4.6 years, p less than 0.01) significantly longer than controls had. Patients in the control group spent significantly more years working full-time than did abusers (6.2 +/- 7.3 vs. 0.7 +/- 1.4, p less than 0.01). There was a nonsignificant trend for abusers with a longer duration of antipsychotic use to have higher Abnormal Involuntary Movement Scale scores (r = 0.40, p less than 0.10). Although these drugs are potentially abusable, the term "anticholinergic abuse" should be reevaluated in light of accumulating evidence that many patients taking these drugs report improved functioning, with improvement in negative symptoms and minimal or no adverse anticholinergic effects.

Adult↗

Pharmacologic management of acute mania in pregnancy.

Mania is a psychiatric illness that often requires immediate intervention, and the pregnant manic patient presents a therapeutic dilemma. Use of psychotropic medications during pregnancy may cause three complications: teratogenesis, neonatal toxicity, and behavioral toxicity. The literature contains few well-controlled studies for psychotropic medications in bipolar or other psychiatric populations and those often lack a control group or do not consider confounding factors such as other drug use. Pharmacologic alternatives include antipsychotics, lithium, carbamazepine, and benzodiazepines. Although studies and case reports describe fetal malformations in infants exposed in utero to psychotropic medications, the data are conflicting as to the nature of anomalies and risk of their occurrence. Malformations can occur in almost every organ system; however, the cardiovascular type are of major concern after lithium exposure during the first trimester and oral clefts after benzodiazepine exposure. Antipsychotic exposure can produce extrapyramidal symptoms in the neonate and lithium has been associated with neonatal cyanosis, lethargy, flaccidity, and non-toxic goiter. A neonatal abstinence syndrome has occurred after maternal benzodiazepine consumption. Behavioral toxicity is more difficult to assess, as long-term follow-up is needed. To date, evidence for behavioral toxicity in children exposed to lithium or antipsychotics in utero is lacking. Few specific guidelines for using psychotropic medications in an acutely manic pregnant patient exist. Current symptoms, past response, and the stage of gestation all must be considered. Complete elimination of symptoms may not be the goal. A team approach is essential in treatment of such a complex and challenging patient.

Acute Disease↗

Clinical outcome and adverse effect profile associated with concurrent administration of alprazolam and imipramine.

Clinical outcome and adverse effects associated with concurrent alprazolam and imipramine administration were studied in 29 patients with major depressive disorder who completed a 6-week trial in which they served as their own controls. Alprazolam was added on Day 8 in gradually escalating, then gradually tapering dosages while imipramine dosages remained unchanged. Significant decreases were observed in scores on the Hamilton Rating Scales for Depression and Anxiety at all later evaluation days with Day 8 as baseline. The mean total Symptom and Side Effects score decreased significantly from Day 8 to Day 22 when alprazolam doses were 1 mg q.i.d. For most side effects, total number of reports remained constant or decreased from Day 1 to later evaluation days. Standing diastolic blood pressures were significantly lower on Day 22 than on Day 1. No significant relationship was found between any rating scale score and plasma concentration data.

Adult↗

An evaluation of population pharmacokinetics in therapeutic trials. Part II. Detection of a drug-drug interaction.

The use of observational data, collected during the routine clinical care of patients, has been advocated as a means to obtain clinically relevant information regarding the pharmacokinetic parameters of drugs. However, the validity of this approach and its proper role in new drug development is unclear. This study was performed to evaluate the ability of three approaches to estimate population pharmacokinetic parameters: the traditional approach, mixed-effect modeling, and a simple pharmacokinetic screen. The evaluation was performed with data collected during a multicenter, open-label study evaluating the efficacy, safety, and pharmacokinetics of imipramine and alprazolam in combination. The traditional pharmacokinetic study demonstrated a 20% decrease in the clearance of imipramine in the presence of 4 mg/day alprazolam. Mixed-effect modeling extends these findings by suggesting that the interaction is dependent on the simultaneous concentration of alprazolam, a finding that was not possible under the study design typically used for traditional pharmacokinetic studies. Although the simple screen suggests the presence of the drug-drug interaction, limited information regarding pharmacokinetic parameters is available and those parameters that can be estimated are biased.

Adult↗

The effect of ranitidine and cimetidine on imipramine disposition.

The pharmacokinetic characteristics of imipramine were studied after a single, oral, 100 mg dose was taken by 12 healthy male subjects following 3 days of pretreatment with placebo, cimetidine (300 mg every 6 h), and ranitidine (150 mg every 12 h) in a randomized, double blind, crossover trial. After each imipramine dose plasma samples were collected for 72 h and assayed for imipramine, desipramine, 2-hydroxyimipramine and 2-hydroxydesipramine by HPLC. Cimetidine preadministration statistically prolonged imipramine t 1/2 compared to ranitidine (22.7 vs. 13.0 h) or placebo (10.8 h). Mean imipramine area under the curve (AUC) following cimetidine pretreatment was more than double that following placebo (2.633 vs. 0.966 micrograms X h X ml-1) or ranitidine (1.14 micrograms X h X ml-1) pretreatment. Imipramine apparent oral clearance was reduced in all 12 subjects after cimetidine. Compared to ranitidine or placebo, cimetidine pretreatment was associated with an increased imipramine/desipramine AUC ratio, suggesting cimetidine-induced impairment of demethylation of imipramine. Ranitidine was not observed to alter imipramine pharmacokinetics.

Administration, Oral↗

Level of pharmacy practice and job satisfaction of adult clinical and psychopharmacy pharmacists.

Two hundred fifty questionnaires were mailed to randomly selected members of the Psychopharmacy Special Interest Group (PS) and Adult Clinical Special Interest Group (ACS) of the American Society of Hospital Pharmacists. Questionnaires were designed to demographically characterize each group and compare levels of job satisfaction, job characteristics, sources of conflict, and levels of practice in pharmacy-based, clinical, educational, and administrative activities. Both groups were found to be slightly satisfied to satisfied with their jobs. PS members were significantly more satisfied than ACS members with the amount of visible impact their work had on their patients. Administrators and physicians were the greatest source of conflict for both groups. Individual job satisfaction items that correlated most strongly with overall job satisfaction were opportunity to do something meaningful, degree of job challenge, and opportunity to utilize skills. Careful attention to these aspects of practice by skilled administrators may enhance job satisfaction in the practice areas studied.

Employment↗

Evaluating the impact of education by a clinical pharmacist on antibiotic prescribing and administration in an acute care state psychiatric hospital.

An antibiotic utilization review program was implemented by a clinical pharmacist in an acute care state psychiatric facility. Antibiotic utilization was concurrently audited in 61 antibiotic orders, written for 48 patients, in order to determine antibiotic prescribing and administration practices and problems. Interventions, consisting of educational presentations, problem-solving meetings, and distribution of written educational materials, were provided by a clinical pharmacist to improve antibiotic prescribing and administration practices. A second audit of 68 antibiotic orders written for 47 patients was concurrently audited after completion of the interventions. When prescribing problems were detected, the clinical pharmacist made recommendations to the prescribing physician. Statistically significant changes in the use of culture and sensitivity tests, appropriate dosage regimens, correct antibiotic administration, and selection of cost-effective therapy were found after all educational interventions were provided. A positive trend not resulting in statistical significance was noted for documentation of infectious disease and selection of appropriate antibiotic agents. This study demonstrates a drug utilization review role for clinical pharmacist's involvement in the acute care psychiatric facility, and illustrates one method by which clinical pharmacists can provide educational programs to improve nonpsychotropic drug prescribing and administration in this setting.

Adolescent↗

Factors associated with the elderly falling in intermediate care facilities.

In intermediate care facilities, the records of 41 patients who had fallen and 36 controls were reviewed retrospectively, and the two groups compared for demographics, diagnoses, blood pressures over the prior two months, and prescribed medication. Seven of the sample had a recent weight loss recorded; all seven were in the group that fell. The mean number of medications prescribed for the group of fallers was significantly greater than the mean prescribed for the control group. The mean number of medication changes during the two weeks prior to the fall was significantly greater than the mean number of medication changes during the two weeks prior to data collection for the control group. Our data suggest that caution should be exercised in multiple drug prescribing for patients in intermediate care facilities and that recent weight loss and medication changes may be risk factors for falling.

Accident Prevention↗

Chemistry, pharmacology, pharmacokinetics, adverse effects, and efficacy of the antidepressant maprotiline hydrochloride.

Maprotiline, a tetracyclic antidepressant with sedative properties, exhibits strong inhibitory effects on norepinephrine uptake across nerve cell membranes but interferes relatively little with serotoninergic mechanisms. The biological half-life of unchanged maprotiline in blood averages 43 hours. Though several studies suggest a more rapid onset of antidepressant effects with maprotiline than with amitriptyline or imipramine, this issue remains unresolved. The adverse effect profile of maprotiline is similar to that of the tricyclic antidepressants, except that rashes are about twice as frequent with maprotiline as with amitriptyline or imipramine. The most frequent adverse reactions are anticholinergic effects and sedation. Data suggest less frequent and severe anticholinergic side effects with maprotiline than with amitriptyline. Maprotiline may be less likely to induce orthostatic hypotension and tachycardia than standard tricyclic antidepressants, but clinically important differences in cardiovascular effects remain to be conclusively demonstrated. Many patients benefit from the convenience of once daily dosing. Maprotiline is comparable in antidepressant efficacy to the tricyclic antidepressants.

Anthracenes↗