Biomedical subjects

P J Perry

Publications and source records attributed to P J Perry.

At least 55 records · Page 3Linked to original sources

PubMed1996

The effect of exogenous testosterone on total and free prostate specific antigen levels in healthy young men.

PURPOSE: We evaluated the effect of exogenous testosterone administration on serum total and free prostate specific antigen (PSA) in healthy young men. MATERIALS AND METHODS: Nine volunteers received either 100, 250 or 500 mg. testosterone by intramuscular injection each week for 15 weeks. Blood was drawn every other week for 28 weeks and at week 40. Serum total and free PSA, and total and free testosterone were measured and compared to baseline values. RESULTS: Significant elevations in total and free testosterone occurred but no significant change in serum total and free PSA was detected. CONCLUSIONS: Serum PSA is not responsive to elevated serum testosterone levels in healthy young men. PSA metabolism in the normal prostate is unclear but our findings may have implications for differentiation of pathological conditions of the human prostate.

Adult↗

PubMed1996

Steroids.

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Anabolic Agents↗

PubMed1995

Nefazodone: a new antidepressant.

The chemistry, pharmacology, pharmacokinetics, and clinical efficacy of nefazodone hydrochloride, a new antidepressant, are described. Nefazodone enhances serotonin (5-hydroxytryptamine [5-HT]) synaptic transmission by acting as an antagonist at 5-HT2 receptors and by inhibiting the reuptake of 5-HT. These two mechanisms combined may enhance 5-HT1A-mediated transmission. In addition, nefazodone weakly inhibits the reuptake of norepinephrine. Nefazodone is a structural analogue of trazodone but is pharmacologically distinct. In placebo-controlled trials, nefazodone was as effective as imipramine for the treatment of major depression and produced clinical benefits in patients with depression-related anxiety and sleep disturbances. More than 2000 patients have received nefazodone in clinical trials. The most commonly reported adverse drug reactions (ADRs) are asthenia, somnolence, dry mouth, nausea, constipation, dizziness, lightheadedness, confusion, abnormal vision, and blurred vision. The incidence of sexual-dysfunction ADRs may be less than that reported for other antidepressants. Nefazodone does not inhibit rapid-eye movement sleep. Nefazodone, an inhibitor of the hepatic P-450 isoenzyme CYP3A4, may increase concentrations of drugs metabolized by this isoenzyme, such as terfenadine, astemizole, triazolam, alprazolam, and midazolam. Caution should be exercised in administering nefazodone hydrochloride with triazolobenzodiazepines, and coadministration with terfenadine or astemizole is contra-indicated. The dosage should start at 100 mg twice daily and then be increased, depending on occurrence of ADRs and the patient's clinical response, to 300-600 mg daily. In elderly or debilitated patients, the initial dosage should be half the usual dosage. Nefazodone hydrochloride is as effective as other available antidepressants and may cause fewer ADRs.

Animals↗

PubMed1995

Clinical use of the newer antipsychotic drugs.

The clinical use of clozapine and risperidone is reviewed. Traditional antipsychotic drugs are effective for treating the positive symptoms of schizophrenia but have little or no effect on the negative symptoms of this disease. Newer antipsychotic agents, such as clozapine and risperidone, are effective for treating both positive and negative symptoms in acutely ill and treatment-resistant patients. Clozapine and risperidone also have a lower incidence of extrapyramidal symptoms (EPS) than traditional antipsychotic drugs. Three hypotheses have been proposed to account for the newer agents' ability to relieve negative symptoms: (1) Improvement in negative symptoms may be linked to improvement in positive symptoms. (2) Negative symptoms may improve in the absence of the EPS often caused by traditional agents. (3) The newer antipsychotic agents may directly affect the neural circuits that trigger negative symptoms.

Adult↗

PubMed1995

Bupropion versus methylphenidate in the treatment of attention-deficit hyperactivity disorder.

OBJECTIVE: In the treatment of attention-deficit hyperactivity disorder (ADHD), the efficacy of the tricyclic antidepressants and monoamine oxidase inhibitor antidepressants has been compared with that of both placebo and the stimulants (methylphenidate and/or dextroamphetamine). However, the effectiveness of bupropion has been contrasted only with placebo. The primary aim of this study was to contrast the efficacy of bupropion with that of methylphenidate in the treatment of ADHD. METHOD: A double-blind, crossover design was used in this study. After a 14-day medication washout period, 15 ADHD subjects (7 to 17 years old) were randomized to either methylphenidate or bupropion for 6 weeks, washed out for an additional 2 weeks, and then "crossed over" to the other drug. Methylphenidate was titrated to the maximum effective dose of 0.4 to 1.3 mg/kg per day (mean 0.7 mg/kg per day) and bupropion was titrated to an effective dose ranging from 1.4 to 5.7 mg/kg per day (mean 3.3 mg/kg per day). RESULTS: Both methylphenidate and bupropion produced significantly greater (p < .001) and equivalent improvement on the Iowa-Conners Teacher's Rating Scale according to both the subjects' parents and teachers. The same pattern of improvement was also noted for improvement on the Clinical Global Impression Scale, Kagan's Matching Familiar Figures Test, Continuous Performance Test, Children's Depression Inventory, Children's Manifest Anxiety Scale, and Rey Auditory-Verbal Learning Test. CONCLUSIONS: In this double-blind, crossover trial, bupropion and methylphenidate were both effective and did not differ in their overall efficacy as treatments for ADHD.

Adolescent↗

PubMed1994

Venlafaxine: a heterocyclic antidepressant.

The pharmacology, pharmacokinetics, and clinical efficacy of venlafaxine hydrochloride, a new antidepressant, are described. Venlafaxine inhibits the reuptake of serotonin, norepinephrine, and, to a lesser extent, dopamine. In animal models, it does not significantly inhibit muscarinic, histaminic, or adrenergic receptor activity and does not inhibit monoamine oxidase. Venlafaxine is rapidly absorbed and metabolized in the liver to its active metabolite, O-desmethylvenlafaxine (ODV). Time to peak concentration is one to two hours for the parent compound and four to five hours for ODV. The pharmacokinetics of venlafaxine might be dose-dependent, although pharmacokinetic studies have had conflicting results. The major route of elimination is renal; thus, patients with renal dysfunction may require lower doses. In double-blind, placebo-controlled trials of venlafaxine for maintenance therapy, venlafaxine has shown effective antidepressant activity in severely ill patients with major depression. Antidepressant effectiveness may be apparent within two weeks; this finding needs to be replicated. The dosage is 75-375 mg/day administered in two or three divided doses. The strength of the antidepressant response may be correlated with increasing dosage. Nausea is the most commonly reported adverse drug reaction (ADR). Others include somnolence, dizziness, dry mouth, and sweating. All ADRs have commonly occurred at the beginning of therapy and decreased with time. Overall, venlafaxine is well tolerated. Venlafaxine is as effective as other available antidepressants. It may cause fewer anticholinergic, antihistaminic, and antiadrenergic ADRs and may have a quicker onset of therapeutic action than existing antidepressants.

Antidepressive Agents, Second-Generation↗

PubMed1994

Structure-activity studies on 2-aryl-4H-3,1-benzoxazin-4-ones.

Eight benzoxazin-4-ones related in structure to NSC 341964 (1) have been tested for cytotoxicity in two different cell systems. Two of the benzoxazin-4-ones (3 and 10) showed good cytotoxicity (ID50 = 9.9 and 8.9 microM) in P388 cells. The nitrobenzoxazin-4-one (10) caused a significant alteration in cell cycle distribution when administered to P388 cells and was an inhibitor of porcine pancreatic elastase. Structure-activity relationships are discussed.

Animals↗

PubMed1994

Sertraline-phenelzine drug interaction: a serotonin syndrome reaction.

OBJECTIVE: To report a serious drug interaction possibly occurring with the monoamine oxidase inhibitor phenelzine and the selective serotonin reuptake inhibitor sertraline. CASE SUMMARY: A 61-year-old woman with treatment-refractory major depressive disorder was being treated unsuccessfully with lithium, phenelzine, thioridazine, and doxepin. Sertaline 100 mg/d was added to the patient's therapy. Within three hours of ingesting the first dose, the patient experienced a dramatic increase in her temperature, pulse, and respirations along with labile blood pressure, and symptoms of rigidity, diaphoresis, shivering, and decreased sensorium. The patient was transported to the emergency room and treated with diazepam 10 mg iv, followed by midazolam 10 mg iv for control of rigidity. She was also intubated. The patient then experienced precipitous falls in her blood pressure and respiratory rate. Ice packs combined with a cooling blanket and dantrolene 80 mg iv were administered to control fever and rigidity, respectively. She had an initial working diagnosis of neuroleptic malignant syndrome, which was later changed to serotonin syndrome. Dantrolene was continued for 72 hours at which time the patient was extubated and transferred to a psychiatric unit. CONCLUSIONS: Selective serotonin reuptake inhibitor antidepressants should not be combined with monoamine oxidase inhibitor antidepressants because of the risk of serotonin syndrome.

1-Naphthylamine↗

PubMed1994

Plasma clozapine concentrations as a predictor of clinical response: a follow-up study.

We investigated the relationship between plasma clozapine concentrations and clinical response in treatment-refractory schizophrenic patients. In a previous study, we found that plasma drug concentrations above 350 ng/mL maximized clinical response in a group of 29 patients. This study represents a follow-up of these original 29 patients over approximately 2 1/2 years of clozapine treatment. We found that during the initial 6-week trial of clozapine, 38% (N = 11) of the patients were considered to be responders. With continued treatment, we found that 58% (14 of 24) were classified as responders. Consistent with our previous study, we observed that plasma concentrations were helpful in predicting response. Five of 7 patients who had unsatisfactory response became responders when their plasma clozapine concentrations increased to above 350 ng/mL. We conclude that the assessment of plasma clozapine concentrations as a guide to dose adjustment may be useful in maximizing response.

Adult↗

PubMed1994

Tricyclic antidepressant concentrations in plasma: an estimate of their sensitivity and specificity as a predictor of response.

An analysis of the literature on tricyclic antidepressant level in blood using receiver operating characteristics curves as the primary statistical tool was performed. For nortriptyline, a significant curvilinear relationship between therapeutic response and nortriptyline was observed that ranged from 58 to 148 ng/ml. The sensitivity and specificity for the nortriptyline therapeutic window were 78 and 61%, respectively. The response rate within the therapeutic range was 66% versus 26% outside the therapeutic range. For desipramine, a significant linear relationship between therapeutic response and desipramine concentration in plasma was observed. The threshold concentration in plasma for therapeutic response was 116 ng/ml. The sensitivity and specificity for the desipramine threshold level in blood were 81 and 59%, respectively. The response rate above the threshold level was 51% versus 15% below the therapeutic threshold concentration. For imipramine, a significant curvilinear relationship between therapeutic response and total imipramine (imipramine+desipramine) concentration in plasma was observed between 175 and 350 ng/ml. The sensitivity and specificity for the total imipramine concentrations in plasma were 52 and 74%, respectively. The response rate within the therapeutic range was 67% versus 39% outside the therapeutic range. For amitriptyline, a significant curvilinear relationship between therapeutic response and total amitriptyline (amitriptyline+nortriptyline) concentration in plasma was observed between 93 and 140 ng/ml. The sensitivity and specificity for the total imipramine concentrations in plasma were 37 and 80%, respectively. The response rate within the therapeutic range was 50% versus 30% outside the therapeutic range.

Adolescent↗

PubMed1993

Zolpidem: a nonbenzodiazepine hypnotic for treatment of insomnia.

The pharmacology, pharmacokinetics, and clinical efficacy of zolpidem tartrate, a new hypnotic agent, are described. Zolpidem belongs to the imidazopyridine class. It exhibits high-affinity binding at a benzodiazepine-receptor subtype that is located in the cerebellum and cerebral cortex but not in the spinal cord or peripheral tissues. It decreases sleep latency and increases total sleep time and sleep efficiency without affecting sleep architecture. Zolpidem tartrate is absorbed rapidly. Bioavailability is 67% after oral doses of 5-20 mg. Pharmacokinetics show age-related and sex-related variations. The disposition of zolpidem is reduced in hepatically and renally impaired patients. Clinical studies have shown effectiveness of zolpidem in increasing sleep time and decreasing sleep latency. It has demonstrated efficacy equal to that of benzodiazepines without causing rebound insomnia or withdrawal effects. Comparative trials have found zolpidem as effective as flunitrazepam, flurazepam, and triazolam. The optimum dose of zolpidem tartrate is 10 mg at bedtime; 5 mg for elderly patients. Adverse reactions to zolpidem are dose-related and have primarily CNS and gastro-intestinal manifestations. Zolpidem exhibits similar efficacy to the benzodiazepines in the treatment of insomnia. Zolpidem's advantages over benzodiazepines are that it does not lead to tolerance, withdrawal phenomena, or REM rebound; however, for short-term, as-needed use, these advantages are not relevant.

Clinical Trials as Topic↗

PubMed1993

Haloperidol dosing requirements: the contribution of smoking and nonlinear pharmacokinetics.

Previous data suggest the possibility that haloperidol daily dosing requirements may be confounded by smoking and, at higher doses, capacity-limited metabolism. Forty hospitalized patients suffering from an acute exacerbation of schizophrenia were treated for 2 weeks with fixed oral doses of haloperidol ranging from 10 to 70 mg/day (0.13 to 0.95 mg/kg/day) that produced mean steady-state concentrations between 4.5 and 55.4 ng/ml. No significant differences between the smoking and nonsmoking groups were obvious for the factors of weight, age, sex, daily doses, steady-state clearance, and steady-state haloperidol concentrations in plasma at week 1, week 2, and their mean. The hypothesis that the relationship between haloperidol dose and steady-state haloperidol concentration in plasma was affected by patients' smoking status and metabolic capacity was tested by multiple linear regression analysis and initially rejected. The relationship of dose to haloperidol concentration was fitted as a linear function. To improve the curve fit, the haloperidol concentrations and doses were transformed to their natural logs and then the regression line was refitted. The multiple regression analysis was repeated with the data in their transformed state. It was found that, although smoking status and dose of the drug did not independently affect the average haloperidol concentration, together they interacted in such a way that individual haloperidol concentrations were dependent on the smoking status at specific doses. Thus, two haloperidol dosing equations were generated, one for smokers and one for nonsmokers.

Adult↗

PubMed1992

The efficacy of ergogenic agents in athletic competition. Part I: Androgenic-anabolic steroids.

OBJECTIVE: To summarize the literature describing the epidemiology, pharmacology, efficacy, and adverse effects associated with androgenic-anabolic steroid (AAS) use among athletes. DATA SOURCES: Relevant articles were identified from a MEDLINE search using the search terms "Doping in Sports," "Anabolic Steroids (exploded)," and "Androgens (exploded)." Additional references were found in the bibliographies of these articles. STUDY SELECTION/DATA EXTRACTION: We reviewed studies of AAS use among professional athletes. Interpretation of these studies is difficult because of poor research design. The efficacy studies lacked adequate placebo control. Much of the literature describing adverse effects consists of anecdotal reports. All of this literature was considered for review. DATA SYNTHESIS: Of all ergogenic drugs, AASs are the most widely abused. Abuse of AASs among high school students is estimated at five to ten percent. AASs are hypothesized to produce ergogenic effects during periods of concomitant positive nitrogen balance via antagonism of the catabolic effect of glucocorticoids released during intense exercise. Despite years of study, the extent of the ergogenic effects associated with AASs remains unclear. This may be because most studies have failed to approximate athletes' AAS usage patterns. The primary toxic effects of AASs are divided into four areas: hepatic, reproductive, cardiovascular, and psychiatric. Athletes do not consider these effects severe enough to refrain from using these drugs. CONCLUSIONS: Athletes view AASs as an essential component for success. Without adequate intervention measures, AAS abuse is likely to continue unchecked.

Anabolic Agents↗

PubMed1992

The efficacy of ergogenic agents in athletic competition. Part II: Other performance-enhancing agents.

OBJECTIVE: To summarize the literature describing the epidemiology, pharmacology, efficacy, and adverse effects associated with growth hormone (GH), caffeine, aerobic metabolism facilitator (AMF), and sympathomimetic use among athletes. DATA SOURCES: Relevant articles were identified from a MEDLINE search using the search terms "Doping in Sports," "Blood," "Caffeine," "Cocaine," "Erythropoietin," "Somatotropin," and "Sympathomimetics (exploded)." Additional references were found in bibliographies of these articles. STUDY SELECTION/DATA EXTRACTION: We reviewed studies of ergogenic drug (ED) use among athletes. Interpretation of these studies is difficult because of poor research design and the paucity of information available. This necessitated the inclusion of many anecdotal or conjectural reports in our review. DATA SYNTHESIS: There are no studies documenting an ergogenic effect associated with GH use in humans or animals. It is still unknown whether GH abuse causes adverse effects in healthy adults, although GH-induced acromegaly has been suspected. Amphetamines, cocaine, and caffeine are thought to improve performance via enhanced concentration among athletes. Amphetamines and cocaine may increase aggressiveness. The ergogenic effects of other sympathomimetics including ephedrine and phenylpropanolamine are unclear. AMFs (e.g., blood doping, epoetin) enhance aerobic metabolism and endurance by increasing the oxygen-carrying capacity of the blood. Risks associated with excessive AMF use include increased blood viscosity and clotting. CONCLUSIONS: Athletes view EDs as an essential component for success. Without adequate intervention measures, ED abuse is likely to continue unchecked.

Amphetamines↗

PubMed1992

Nonneuroleptic treatment of disruptive behavior in organic mental syndromes.

OBJECTIVE: To summarize the literature describing nonneuroleptic treatments of unacceptably disruptive behavior in chronically institutionalized psychiatric patients with mental retardation, autism, organic brain syndrome, and dementia. DATA SOURCES: Relevant articles were identified from a MEDLINE search of the above diagnoses linked with "aggression" and "psychomotor agitation." Additional references were found in the bibliographies of these articles. STUDY SELECTION/DATA EXTRACTION: The studies reviewed were limited to prospective evaluations of nonneuroleptic drug therapy of these behavior disturbances. Case reports, case series, and retrospective studies were excluded. Studies of patients with schizophrenia, affective disorders, and personality disorders were also excluded. DATA SYNTHESIS: Studies of lithium, beta-blockers, carbamazepine, benzodiazepines, and buspirone were adequate for review. As a rule, these studies are hampered by poor design. The lithium studies suggest that mentally retarded patients with behavior disturbances may respond to lithium treatment. The beta-blocker studies suggest improvement in patients with mental retardation, autism, organic brain syndrome, and dementia. Neuroleptic discontinuation or a decrease in dose was possible in some patients. The carbamazepine studies were inconclusive. Carbamazepine should be reserved for patients with concomitant seizure disorders. Benzodiazepines were helpful in treating elderly demented patients. Thus far, buspirone has been evaluated in only a few, poorly designed studies and is not yet recommended for treatment of behavior disturbances. CONCLUSIONS: Legislation has restricted the use of neuroleptics in many patients receiving long-term healthcare. Despite the questionable validity of the studies reviewed, lithium, beta-blockers, carbamazepine, and benzodiazepines may be considered as alternatives to neuroleptics in selected cases.

Adrenergic beta-Antagonists↗

PubMed1991

Detoxification from benzodiazepines: schedules and strategies.

Management of benzodiazepine (BZD) tolerance is divided into low- and high-dose withdrawal. Low-dose withdrawal includes patients who have received manufacturer-recommended doses of BZD on a daily basis for longer than 1 month. Gradual tapering of the BZD over 4 weeks on an outpatient basis is suggested. High-dose withdrawal includes patients who have been ingesting doses of BZD greater than the equivalent of diazepam 40 mg/d for longer than 8 months. It is recommended that the patients be tolerance tested with diazepam and, if tolerant, tapered off medication as inpatients at a rate of 10% per day. Triazolobenzodiazepines may be exceptions to these recommendations. Alprazolam should be titrated at a rate of 0.5 mg three times a day regardless of whether the patient is being tapered for low- or high-dose withdrawal.

Anti-Anxiety Agents↗

PubMed1991

The assay of clozapine and N-desmethylclozapine in human plasma by high-performance liquid chromatography.

A high performance liquid chromatographic method for the simultaneous quantitation of clozapine--a member of the dibenzodiazepine class of antipsychotic drugs--and its reduced metabolite in human plasma has been developed. Clozapine and N-desmethylclozapine are concentrated from blood samples by liquid-liquid extraction, followed by reverse-phase liquid chromatography. Accuracy of the determination is ensured by application of an internal standard, protriptyline, which is closely related to clozapine. A detection limit of 15 ng/mL for clozapine and 30 ng/ml for N-desmethylclozapine was achieved.

Chromatography, High Pressure Liquid↗

PubMed1991

Clozapine and norclozapine plasma concentrations and clinical response of treatment-refractory schizophrenic patients.

OBJECTIVE: Clozapine, an atypical antipsychotic, has been estimated to be effective in 30% of treatment-refractory schizophrenic patients. The authors hypothesized that if a dose-response relationship was obvious for this drug, the response rate could be significantly amplified. METHOD: Following an 8-24-day dose titration phase, 29 inpatients with treatment-resistant schizophrenia diagnosed according to DSM-III-R were given a clozapine dose of approximately 400 mg/day for 4 weeks; blood samples were obtained weekly during this period. RESULTS: A receiver operator curve demonstrated that the threshold clozapine plasma concentration for therapeutic response was 350 ng/ml. Sixty-four percent of the patients with clozapine plasma concentrations greater than 350 ng/ml responded, whereas only 22% of the patients with concentrations less than 350 ng/ml responded. CONCLUSIONS: Use of clozapine blood levels as a predictor for treatment response in treatment-refractory schizophrenic patients appears worthwhile, since the measurement's sensitivity for response was 64% and the specificity for nonresponse was 78%.

Adult↗