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J S Markowitz

Publications and source records attributed to J S Markowitz.

At least 19 recordsLinked to original sources
PubMed2001

A high-performance liquid chromatography assay with ultraviolet detection for olanzapine in human plasma and urine.

Olanzapine is a commonly used atypical antipsychotic medication for which therapeutic drug monitoring has been proposed as clinically useful. A sensitive method was developed for the determination of olanzapine concentrations in plasma and urine by high-performance liquid chromatography with low-wavelength ultraviolet absorption detection (214 nm). A single-step liquid-liquid extraction procedure using heptane-iso-amyl alcohol (97.5:2.5 v/v) was employed to recover olanzapine and the internal standard (a 2-ethylated olanzapine derivative) from the biological matrices which were adjusted to pH 10 with 1 M carbonate buffer. Detector response was linear from 1-5000 ng (r2>0.98). The limit of detection of the assay (signal:noise=3:1) and the lower limit of quantitation were 0.75 ng and 1 ng/ml of olanzapine, respectively. Interday variation for olanzapine 50 ng/ml in plasma and urine was 5.2% and 7.1% (n=5), respectively, and 9.5 and 12.3% at 1 ng/ml (n=5). Intraday variation for olanzapine 50 ng/ml in plasma and urine was 8.1% and 9.6% (n=15), respectively, and 14.2 and 17.1% at 1 ng/ml (n=15). The recoveries of olanzapine (50 ng/ml) and the internal standard were 83 +/- 6 and 92 +/- 6% in plasma, respectively, and 79 +/- 7 and 89 +/- 7% in urine, respectively. Accuracy was 96% and 93% at 50 and 1 ng/ml, respectively. The applicability of the assay was demonstrated by determining plasma concentrations of olanzapine in a healthy male volunteer for 48 h following a single oral dose of 5 mg olanzapine. This method is suitable for studying olanzapine disposition in single or multiple-dose pharmacokinetic studies.

Antipsychotic Agents↗
PubMed2001

Human monocytic ehrlichiosis: an emerging pathogen in transplantation.

BACKGROUND: The spectrum of disease caused by Ehrlichia spp. ranges from asymptomatic to fatal. Awareness and early diagnosis of the infection is paramount because appropriate therapy leads to rapid defervescence and cure. If left untreated, particularly in immunosuppressed patients, ehrlichioses may result in multi-system organ failure and death. METHODS: We report the second case of human monocytic ehrlichiosis (HME) in a liver transplant recipient, and review the literature. RESULTS: The patient presented with fever and headache, had negative cultures, and despite broad-spectrum antimicrobial coverage appeared progressively septic. After eliciting a history of tick exposure we treated the patient empirically with doxycycline. The diagnosis of HME was confirmed by 1) polymerase chain reaction (PCR) for Ehrlichia chaffeensis, 2) acute and convalescent serum titers, and 3) in vitro cultivation of E chaffeensis from peripheral blood. CONCLUSION: Although human ehrlichioses are relatively uncommon, they are emerging as clinically significant arthropod-borne infections. Although epidemiological exposure is responsible for infection, immunosuppression makes patients more likely to succumb to disease. A high index of suspicion and early treatment results in a favorable outcome.

Animals↗
PubMed2001

New onset diabetes and atypical antipsychotics.

As a class, the atypical antipsychotics are the first line treatment choice for the psychopharmacologic management of psychotic disorders. Emerging evidence currently suggests that at least two of the atypical antipsychotics, clozapine and olanzapine, and possibly quetiapine may be associated with the risk of new onset diabetes or serum glucose dyscontrol. Computerized Medline and Current Contents searches from years 1966 through June 2000 were undertaken to retrieve all pertinent studies and case reports of typical and atypical antipsychotics and glucose-insulin problems. Historically, both schizophrenia and the older antipsychotics medications have been reported to be associated with a similar risk for causing disruptions in serum glucose control. Additionally, diabetes has well recognized associations with a number of medical disorders such as cardiovascular disease; it is therefore worthy of attention. Hypothesized mechanisms for antipsychotic induced diabetes ranges from the antagonism of several neurotransmitter receptors to insulin resistance. A total of thirty-five cases of induced or exacerbated diabetes are presently available in the published literature; the vast majority of cases implicate clozapine (n=20) and olanzapine (n=15). In multiple cases, diabetic ketoacidosis has been the presenting symptom; daily atypical antipsychotic doses have been within acceptable ranges and were not considered to be excessive.

Adult↗
PubMed2001

Liver transplantation in patients with severe portopulmonary hypertension treated with preoperative chronic intravenous epoprostenol.

Portopulmonary hypertension (PPHTN) is no longer an absolute contraindication to orthotopic liver transplantation (OLT). The pre-OLT management of patients with PPHTN requires early diagnosis and chronic therapy with intravenous epoprostenol to decrease pulmonary vascular resistance (PVR). Close follow-up is necessary to reassess pulmonary artery pressures (PAPs) and evaluate right ventricular (RV) function. This assists in the optimal timing of OLT. Successful management also necessitates reassessment of pulmonary artery hemodynamics just before OLT, with clearly defined parameters used to determine whether to proceed. Even with the intraoperative and postoperative availability of potent pulmonary vasodilators, clinical management may be suboptimal in reducing PAP. Adequate reduction in PVR and improvement in RV function in response to chronic epoprostenol therapy may facilitate successful OLT. We present a case report and review the limited experience with this treatment.

Adult↗
PubMed2001

A double-blind placebo-controlled case study of the use of donepezil to improve cognition in a schizoaffective disorder patient: functional MRI correlates.

Cognitive impairment in multiple domains is common in patients with schizophrenia and may be a powerful determinant of poor functional ability and quality of life. We report a double-blind, placebo-controlled, cross-over study of donepezil augmentation in a schizoaffective disorder patient stabilized on olanzapine pharmacotherapy. The patient showed significant improvements in several cognitive measures and increased activation of prefrontal cortex and basal ganglia on functional MRI during the donepezil augmentation. In addition, the donepezil augmentation resulted in a reduction of depressive symptoms and in significant improvements in functional abilities and quality of life. Further studies of donepezil augmentation of neuroleptics in schizophrenia are warranted.

Adult↗
PubMed2001

Drug glucuronidation in clinical psychopharmacology.

Glucuronidation is a phase II metabolic process and one of the most common pathways in the formation of hydrophilic drug metabolites. At least 33 families of uridine diphosphate-glucuronosyltransferases have been identified in vitro, and specific nomenclature similar to that used to classify the cytochrome (CYP) P450 system has been established. The UGT1 and UGT2 subfamilies represent the most important of these enzymes in human drug metabolism. Factors affecting glucuronidation include the following: cigarette smoking, obesity, age, and gender. In addition, several drugs have been found in vitro to be substrates, inhibitors, or inducers of UGT enzymes. Induction or inhibition of both UGT and CYP isoforms may occur simultaneously. Some important drug interactions involving glucuronidation have been documented and others can be postulated. This review summarizes the relevant literature pertaining to drug glucuronidation and its implications for clinical psychopharmacology.

Adolescent↗
PubMed2001

Intranasal sumatriptan in post-ECT headache: results of an open-label trial.

BACKGROUND: Significant headaches occur in up to 45% of patients receiving electroconvulsive therapy (ECT) as a result of treatment. Headaches may at times be severe and affect patient compliance with this treatment modality. The 5-HT(1B/1D) receptor agonist sumatriptan has been reported to be effective for post-ECT headache in several case reports. The aim of the present open-label study was to assess the efficacy and tolerability of intranasal sumatriptan for post-ECT headache. METHOD: Patients undergoing ECT who experienced moderate-to-severe post-ECT headache were enrolled in the study. Patients were asked to rate their headache severity and describe headache characteristics using a standard headache diary. Headaches rated as severe or moderate were treated with 20 mg of intranasal sumatriptan. Additional headache ratings were recorded at 0.25, 0.5, 1.0, 1.5, and 2 hours after sumatriptan administration and compared with baseline values. RESULTS: Eight female patients (ages 34-45 years old) participated in the trial and experienced a total of 13 post-ECT headaches, which were treated with intranasal sumatriptan. Of the headaches treated, six (46.2%) were described as severe and seven (53.8%) were characterized as moderate in severity. Twelve (92.3%) of the treated headaches responded by the 2 hour posttreatment time point and 11 (84.6%) had responded within 1 hour. Comparisons made at the 1- and 2-hour time point revealed a statistically significant improvement from baseline (p = 0.002). Of the 12 headaches that responded, 6 (50%) were reported as no pain and 5 (38.5%) were reported as only mild pain at 1 hour following treatment. At the 2-hour assessment, an additional headache, which had previously not responded, was rated at mild resulting in six (50%) headaches with complete resolution of pain and six (50%) with a decrease in pain symptoms from moderate or severe to mild. Overall, sumatriptan treatment was well tolerated, and no significant adverse effects or changes in vital signs were recorded. In no case was a second dose of sumatriptan given. The most common complaint was the taste of the medication (n = 4), which was not treatment limiting. No patient withdrew from the study due to an adverse event. CONCLUSION: Intranasal sumatriptan spray may be an effective, well-tolerated, and prompt treatment for patients experiencing moderate-to-severe post-ECT headache. Preventing post-ECT headache may contribute to patient compliance with the ECT treatment modality. Additionally, the known pharmacologic effects of sumatriptan and the generally positive results found in the present study suggest that ECT-induced headache is vascular in origin. Further placebo-controlled, double-blind studies are needed to confirm our open-label results.

Administration, Intranasal↗
PubMed2001

Pharmacokinetic and pharmacodynamic drug interactions in the treatment of attention-deficit hyperactivity disorder.

The psychostimulants methylphenidate, amphetamine and pemoline are among the most common medications used today in child and adolescent psychiatry for the treatment of patients with attention-deficit hyperactivity disorder. Frequently, these medications are used in combination with other medications on a short or long term basis. The present review examines psychostimulant pharmacology, summarises reported drug-drug interactions and explores underlying pharmacokinetic and pharmacodynamic considerations for interactions. A computerised search was undertaken using Medline (1966 to 2000) and Current Contents to provide the literature base for reports of drug-drug interactions involving psychostimulants. These leads were further cross-referenced for completeness of the survey. Methylphenidate appears to be more often implicated in pharmacokinetic interactions suggestive of possible metabolic inhibition, although the mechanisms still remain unclear. Amphetamine was more often involved in apparent pharmacodynamic interactions and could potentially be influenced by medications affecting cytochrome P450 (CYP) 2D6. No published reports of drug interactions involving pemoline were found. The alpha2-adrenergic agonists clonidine and guanfacine have been implicated in several interactions. Perhaps best documented is their antagonism by tricyclic antidepressants and phenothiazines. In additional, concurrent beta-blocker use, or abrupt discontinuation, can lead to hypertensive response. Although there are few published well-controlled interaction studies with psychostimulants and alpha2-adrenergic agonists, it appears that these agents may be safely coadministered. The interactions of monoamine oxidase inhibitors with psychostimulants represent one of the few strict contraindications.

Adrenergic alpha-Agonists↗
PubMed2000

Effect of St. John's wort (Hypericum perforatum) on cytochrome P-450 2D6 and 3A4 activity in healthy volunteers.

The effects of the herb St. John's wort (Hypericum perforatum), a purported antidepressant, on the activity of cytochrome P-450 (CYP) 2D6 and 3A4 was assessed in seven normal volunteers. Probe substrates dextromethorphan (2D6 activity) and alprazolam (3A4 activity) were administered orally with and without the co-administration of St. John's wort. Urinary concentrations of dextromethorphan and dextrorphan were quantified and dextromethorphan metabolic ratios (DMRs) determined. Plasma samples were collected (0-60 hrs) for alprazolam pharmacokinetic analysis sufficient to estimate tmax, Cmax, t 1/2, and AUC. Validated HPLC methods were used to quantify all compounds of interest. No statistically significant differences were found in any estimated pharmacokinetic parameter for alprazolam or DMRs. These results suggest that St. John's wort, when taken at recommended doses for depression, is unlikely to inhibit CYP 2D6 or CYP 3A4 activity.

Adult↗
PubMed2000

Oral nutritional supplementation for the alcoholic patient: a brief overview.

Approximately 1.5 million Americans seek treatment for alcoholism annually. Malnutrition is frequently observed in the alcoholic population due to several factors, including poor dietary intake, alcohol-associated gastrointestinal problems, decreased nutrient absorption and enhanced excretion of trace elements. The administration of multivitamins with minerals and folic acid is commonplace. The present paper reviews basic nutrient deficits commonly encountered in alcoholic individuals and describes the rationale and basic guidelines for oral replacement therapy.

Administration, Oral↗
PubMed2000

Successful liver transplantation in a patient with Budd-Chiari syndrome caused by homozygous factor V Leiden.

Budd-Chiari syndrome (BCS) is a rare form of portal hypertension characterized by hepatic venous outflow obstruction. Although hematologic disorders are the most common cause of this syndrome, to date, 30% of the cases have been classified as idiopathic. Resistance to activated protein C caused by factor V Leiden is the most common cause of thrombophilia; its role in the pathogenesis of BCS is now becoming apparent. We report successful liver transplantation in a patient with BCS caused by homozygous factor V Leiden. The patient was administered standard heparin anticoagulation until activated protein C resistance was normalized by the liver allograft. Liver transplantation corrected the thrombophilic state. The patient has excellent graft function, is not on anticoagulation therapy, and has had no recurrent venous thrombosis at 5 months posttransplantation. Activated protein C resistance caused by the factor V Leiden mutation may be responsible for idiopathic cases of BCS. To avoid unnecessary long-term anticoagulation after liver transplantation, factor V Leiden should be considered as a pathogenic factor in BCS. In addition, because of the high prevalence of factor V Leiden in the world population, cadaveric organ donors with a history of venous thrombosis should be screened for activated protein C resistance lest thrombophilia be transmitted to the recipient.

Adult↗
PubMed2000

Single-dose pharmacokinetics of methylphenidate in CYP2D6 extensive and poor metabolizers.

Six adults phenotyped as either extensive (N = 4) or poor (N = 2) metabolizers for cytochrome P450 (CYP) 2D6 were given a 10-mg oral dose of methylphenidate (MPH) on two separate occasions with and without quinidine, a potent CYP2D6 inhibitor. Quinidine had no significant effect on the pharmacokinetics of either MPH or ritalinic acid, its major metabolite, in either group of CYP2D6 metabolizers. These data suggest a lack of involvement of CYP2D6 in the metabolism of MPH. Drugs that are inhibitors of CYP2D6 when taken concurrently with MPH should not affect its plasma concentration.

Adolescent↗
PubMed2000

An assessment of selective serotonin reuptake inhibitor discontinuation symptoms with citalopram.

The selective serotonin reuptake inhibitors (SSRIs) have recently been associated with a variety of somatic and psychiatric symptoms upon abrupt drug discontinuation. These symptoms have been variously termed SSRI withdrawal, or SSRI discontinuation syndrome. Although all of the available SSRIs have been reported to cause discontinuation symptoms, some appear to have a greater propensity to cause these adverse events than others. Data from a previously completed placebo-controlled, double-blind study designed to assess citalopram in depression relapse prevention were analysed to assess patients for the emergence of discontinuation effects following randomization to placebo after 8 weeks of active drug treatment. Side-effects that occurred during the first 2 weeks following randomization to active drug (n = 150) or placebo (n = 72) were measured using the UKU unwanted side-effect list. The proportion of patients that experienced one or more events over the 2-week period following randomization was similar in the two groups, and there was no association between citalopram dose prior to randomization and the reporting of symptoms. Most of the events that did occur were mild in intensity and none resulted in discontinuation from the study. Events occurring at a higher frequency in the placebo group were most associated with the central nervous system (CNS). These events may reflect a re-emergence of depressive symptoms, since only 14.8% of patients randomized to placebo who did not relapse experienced CNS events, a low symptom incidence that was non-significant (P = 0.562) compared to patients continuing treatment (10.9%). Therefore, this assessment suggests that any symptoms associated with rapid discontinuation of citalopram are mild and transient, and emphasizes the significant role re-emerging depression and / or anxiety may play in the assessment and identification of SSRI discontinuation symptoms.

Citalopram↗
PubMed2000

Avoiding psychotropic drug interactions in the cardiovascular patient.

Recent advances in our understanding of the hepatic cytochrome P450 inhibitory effects of the newer antidepressants have increased concern about drug interactions in the practice of psychiatry. The authors summarize the potential interactions of psychoactive drugs with cardiovascular medications. Practicing psychiatrists encounter many patients with cardiovascular disease, and an awareness of these interactions will improve knowledgeable prescribing for medically ill patients with comorbid mental disorders.

Cardiovascular Agents↗
PubMed2000

Ethylphenidate formation in human subjects after the administration of a single dose of methylphenidate and ethanol.

Ethylphenidate was recently reported as a novel drug metabolite in two overdose fatalities where there was evidence of methylphenidate and ethanol coingestion. This study explores the pharmacokinetics of ethylphenidate relative to methylphenidate and the major metabolite ritalinic acid, in six healthy subjects who received methylphenidate and ethanol under controlled conditions. Subjects (three males, three females) received a single oral dose of methylphenidate (20 mg; two 10-mg tablets) followed by consumption of ethanol (0.6 g/kg) 30 min later. Methylphenidate, ritalinic acid, and ethylphenidate were quantified using liquid chromatography-tandem mass spectrometry. Ethylphenidate was detectable in the plasma and urine of all subjects after ethanol ingestion. The mean (+/-S.D.) area under the concentration versus time curve for ethylphenidate was 1.2 +/- 0.7 ng/ml/h, representing 2.3 +/- 1.3% that of methylphenidate (48 +/- 12 ng/ml/h). A significant correlation was observed between the area under the concentration versus time curve of methylphenidate and that of ethylphenidate. In view of the known dopaminergic activity of racemic ethylphenidate, it remains possible that under certain circumstances of higher level dosing, e.g., in the abuse of methylphenidate and ethanol, the metabolite ethylphenidate may contribute to drug effects.

Adult↗