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Biomedical subjects

L Ereshefsky

Publications and source records attributed to L Ereshefsky.

At least 55 records · Page 3Linked to original sources
PubMed1986

Effects of smoking on haloperidol and reduced haloperidol plasma concentrations and haloperidol clearance.

Plasma concentrations of haloperidol and its reduced metabolite (reduced haloperidol) were investigated in cigarette smokers (N = 23) and nonsmokers (N = 27). Steady-state plasma concentrations were obtained 12 h post bedtime dose. Haloperidol and reduced haloperidol concentrations were determined by RIA. Reduced haloperidol was separated by selective succinylation and liquid chromatography. Patients were clinically assessed with the Clinical Global Impression Scale (CGIS). Smokers had significantly lower haloperidol and reduced haloperidol plasma concentrations than nonsmokers (P less than 0.01, P less than 0.05). Clearance of haloperidol was significantly greater in smokers compared to nonsmokers (P = 0.0052). CGIS assessments did not show significant differences between smokers and nonsmokers. Plasma concentrations should be carefully monitored when patients either start or stop smoking.

Adult↗
PubMed1986

Bioavailability of psychotropic drugs: historical perspective and pharmacokinetic overview.

The evolution of the federal government's role in the regulation and evaluation of generic psychotropic medications is described. To place many of the methodologic bioequivalence issues for antipsychotic agents into perspective, the pharmacokinetics of these drugs are reviewed. Appropriate methodologies for studying the pharmacokinetics and pharmacodynamics of psychotropic drugs are in early developmental stages. Many of the issues relating to bioequivalence of generic products will not be resolved until a better understanding of these factors is developed.

Biological Availability↗
PubMed1985

Effects of carbamazepine on plasma haloperidol levels.

Plasma haloperidol levels were monitored in three schizophrenic patients when carbamazepine was either added or discontinued. The percent decrease in plasma haloperidol levels due to concomitant carbamazepine therapy was between 59% and 61%. The effects of carbamazepine on plasma haloperidol levels were noted to occur in 2 to 3 weeks. Although no adverse effects occurred in the patients during therapy, careful monitoring of clinical symptoms and plasma haloperidol levels is recommended.

Carbamazepine↗
PubMed1984

Future of depot neuroleptic therapy: pharmacokinetic and pharmacodynamic approaches.

The future of depot neuroleptic therapy is discussed in terms of pharmacokinetic and pharmacodynamic research opportunities. Analytic methods for neuroleptic assays, including chromatographic, radioreceptor, nuclear magnetic resonance, and radioimmunoassay techniques, are briefly reviewed. Elucidation of depot neuroleptic multicompartment kinetics utilizing nonlinear mixed-effects modeling and the usefulness of these data in interpreting plasma levels are discussed. The clinical significance of plasma monitoring of depot fluphenazine, including the development of dosage conversion guidelines, is presented. The relationships between haloperidol and its metabolite reduced haloperidol (RH) are discussed in terms of dosage form and response. Clinical advantages resulting from the availability of more depot neuroleptics are discussed.

Adult↗
PubMed1984

Haloperidol and reduced haloperidol plasma levels in selected schizophrenic patients.

The first measurements of haloperidol (HL) and its reduced metabolite hydroxyhaloperidol (RH) in plasma versus clinical response in five chronic schizophrenic patients are reported. HL and RH were measured by a radioimmunoassay with a low coefficient of variation. Patients were selected based on poor response or the need for high dosage and were rated with the Clinical Global Impression Scale. Daily HL dosage range was 0.5 to 1.5 mg/kg. HL plasma concentrations ranged from 14 to 98 ng/ml. RH plasma concentrations ranged from 10 to 319 ng/ml. Four patients did not respond to HL therapy; two of these improved dramatically when switched to fluphenazine. The four nonresponding patients had higher RH than HL concentrations. RH seems to be present in plasma in significant concentrations, and further investigation of the relationships of RH and HL plasma levels versus response is needed.

Adult↗
PubMed1981

Very high dose loxapine in refractory schizophrenic patients.

The authors report on three chronic, treatment-refractory schizophrenic patients who dramatically improved when placed on very high doses of loxapine (300-500 mg/day). Numbness transiently appeared in two patients at very high doses of loxapine; it may be a frequently occurring but unreported side effect. The relative lack of serious side effects to very high dose loxapine suggests that this may be a useful intervention in carefully selected refractory patients. The authors recommend that controlled studies be done to elucidate the benefit to risk ratio.

Adult↗
PubMed1979

Treatment of tardive dyskinesia and mania with RBC lithium determinations.

The authors report the usefulness of RBC lithium determinations in managing the treatment of tardive dyskinesia. They present a case report in which manic manifestations and tardive dyskinesia symptoms paralleled the rise and fall of RBC lithium and plasma lithium levels were constant during the period of symptom improvement. They conclude that RBC lithium levels appeared to reflect toxicity, control of mania, and symptom suppression of tardive dyskinesia better than plasma lithium levels alone.

Antipsychotic Agents↗
PubMedDate not supplied

Determinants of compliance in epileptic outpatients.

The authors have investigated reasons for medication compliance in a population of epileptic patients. The hypothesis that the health care belief model would be predictive of medication-taking behavior was validated. A pilot study was constructed which investigated the comparative responses of compliant and noncompliant epileptic outpatients to questions regarding demographic, clinical history, and attitudinal characteristics. Noncompliant patients were characterized as having a longer duration of epilepsy, more complicated dosage regimens, and more changes in medication. In addition, noncompliant patients both demonstrated more confusion over medication directions and less insight into the need for anticonvulsants and feared addiction to their medication. They had a lower level of satisfaction with their health care and were more frequently subject to the social complications of epilepsy. The authors suggest that a more holistic approach be taken when attempting to reverse noncompliant behavior.

Adult↗
PubMedDate not supplied

Alternative drug therapies for mania: a literature review.

This article reviews the agents used to treat manic patients. It has been suggested that up to 20 percent of all manic patients are refractory to lithium. We reviewed studies suggesting that drugs affecting the serotoninergic, adrenergic, dopaminergic, and opioid neurotransmission systems, as well as anticonvulsants and others, are possible alternative treatments. Despite the large number of agents used, few large controlled studies carefully examine these interventions. Clinical assessments using specific manic rating scales are lacking in most studies. Among the successful alternative treatments reported, carbamazepine has received the most intensive research. Other suggested therapeutic agents, such as levothyroxine and clorgyline, require additional research to verify their effectiveness. From these pharmacological approaches and an understanding of the pathophysiology of mania, future therapeutic interventions can be formulated.

Anticonvulsants↗
PubMedDate not supplied

Clinical pharmacists' impact on prescribing in an acute adult psychiatric facility.

An analysis is presented of data collected to evaluate the impact of a clinical pharmacy service on an acute psychiatric admitting unit. Retrospective longitudinal drug utilization reviews (RLDUR) were performed one year apart (pre- and post-implementation of services) on the same treatment team. Process measures significantly affected include (percent reduction): total drugs/patient (33.9), number of antipsychotic drugs/patient (38.0), number of anticholinergics started on admission/patient (53.2), and number of doses/patient/d (42.4). Other drug-use parameters significantly affected include: a 42-percent increase in the mean dosage expressed as chlorpromazine equivalents, and a 47-percent reduction in the number of patients on low potency antipsychotic medications. Beneficial outcome was reflected by a faster rate of discharge or transfer to a less restrictive ward environment in the pharmacy study population. The study population also demonstrated a 55.8-percent decrease in their readmission rate to the facility over a one-year follow-up period. Clinical pharmacy services positively affect both process and outcome health care measures.

Acute Disease↗
PubMedDate not supplied

Clinical pharmacokinetics of the depot antipsychotics.

The clinical pharmacokinetics of the 4 depot antipsychotics for which plasma level studies are available (i.e. fluphenazine enanthate and decanoate, haloperidol decanoate, clopenthixol decanoate and flupenthixol decanoate) are reviewed. The proper study of these agents has been handicapped until recently by the necessity of accurately measuring subnanomolar concentrations in plasma. Their kinetic properties, the relationship of plasma concentrations to clinical effects, and conversion from oral to injectable therapy are discussed. The depot antipsychotics are synthesised by esterification of the active drug to a long chain fatty acid and the resultant compound is then dissolved in a vegetable oil. The absorption rate constant is slower than the elimination rate constant and therefore, the depot antipsychotics exhibit 'flip-flop' kinetics where the time to steady-state is a function of the absorption rate, and the concentration at steady-state is a function of the elimination rate. Fluphenazine is available as both an enanthate and decanoate ester (both dissolved in sesame oil), although the decanoate is more commonly used clinically. The enanthate produces peak plasma concentrations on days 2 to 3 and declines with an apparent elimination half-life (i.e. the half-time of the apparent first-order decline of plasma concentrations) of 3.5 to 4 days after a single injection. The decanoate produces an early high peak which occurs during the first day and then declines with an apparent half-life ranging from 6.8 to 9.6 days following a single injection. After multiple injections of fluphenazine decanoate, however, the mean apparent half-life increases to 14.3 days, and the time to reach steady-state is 4 to 6 weeks. Withdrawal studies with fluphenazine decanoate suggest that relapsing patients have a more rapid plasma concentration decline than non-relapsing patients, and that the plasma concentrations do not decline smoothly but may exhibit 'lumps' due to residual release from previous injection sites or multicompartment redistribution. Cigarette smoking has been found to be associated with a 2.33-fold increase in the clearance of fluphenazine decanoate. In 3 different studies, fluphenazine has been proposed to have a therapeutic range from less than 0.15 to 0.5 ng/ml with an upper therapeutic range of 4.0 ng/ml. Plasma concentrations following the decanoate injection are generally lower than, but clinically equivalent to, those attained with the oral form of the drug. Haloperidol decanoate plasma concentrations peak on the seventh day following injection although, in some patients, this peak may occur on the first day.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMedDate not supplied

Sleep disorders: assisting patients to a good night's sleep.

Sleep is an active process consisting of macro- and microarchitectural rhythms, chronobiology, and neurochemical changes. Disruptions in sleep chronobiology, which may occur in shift workers and the elderly or due to jet lag, often respond to exogenous melatonin. Insomnia requires careful evaluation to determine contributions of comorbid medical conditions and drug effects. Treatment options include sleep hygiene principles and sedative hypnotic therapy. Zaleplon and zolpidem, short-acting benzodiazepines selective for omega-1 GABA receptors, are effective first-line agents for initiating sleep.

Humans↗