Stereoselective Pharmacokinetics and Pharmacodynamics of Anti-Asthma Agents

2002 ◽  
Vol 36 (4) ◽  
pp. 693-701 ◽  
Author(s):  
Majid Vakily ◽  
Reza Mehvar ◽  
Dion Brocks
Keyword(s):  
English Language ◽  
Data Extraction ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Chiral Drugs ◽  
Medline Search ◽  
Secondary Sources ◽  
Asthmatic Patients ◽  
Stereoselective Pharmacokinetics

OBJECTIVE: To review the previously published studies on pharmacokinetics and pharmacodynamics of chiral drugs used in the treatment of asthma. DATA SOURCES: Primary and review articles were identified with a MEDLINE search (1980–May 2001) and through secondary sources. STUDY SELECTION AND DATA EXTRACTION: All English-language studies and reviews obtained from the MEDLINE search pertaining to stereoselective pharmacokinetics and pharmacodynamics of chiral anti-asthma drugs were assessed. DATA SYNTHESIS: Several anti-asthma drugs (e.g., β2-adrenergic agonists, leukotriene modifiers) are chiral and marketed as racemates, which consist of equal proportions of 2 enantiomers. Significant stereoselectivity has also been reported in pharmacodynamics and pharmacokinetics of the β2-agonists. The enantiomers of β2-agonists in the R configuration are primarily responsible for the bronchodilating effects of the racemate. The plasma concentrations of the enantiomers of anti-asthma drugs may differ as a reflection of stereoselectivity in clearance, volume of distribution, and route of administration. CONCLUSIONS: Stereoselectivity in the pharmacokinetics of anti-asthma drugs may complicate the relationship between dose and/or plasma concentration of racemic drug versus effect relationship. An appreciation of the stereoselective pharmacokinetics and pharmacodynamics of chiral anti-asthma drugs may optimize the use of these agents in asthmatic patients.

Oral Oxymorphone for Pain Management

2007 ◽  
Vol 41 (7-8) ◽  
pp. 1144-1152 ◽  
Author(s):  
Kevin W Chamberlin ◽  
Mark Cottle ◽  
Rebecca Neville ◽  
Jennifer Tan
Keyword(s):  
Pain Management ◽  
Opioid Receptor ◽  
Severe Pain ◽  
English Language ◽  
Therapeutic Option ◽  
Data Extraction ◽  
Plasma Concentrations ◽  
Opioid Agonist ◽  
Safety And Efficacy ◽  
Medline Search

Objective To describe the pharmacology, safety and efficacy, and rationale for use of oral oxymorphone for the management of acute and chronic moderate-to-severe pain. Data Sources A PubMed/MEDLINE search (1966-March 2007) was conducted using the following terms: oral oxymorphone, oxymorphone, EN 3202, EN 3203, Opana, and Opana ER. Manufacturer-provided data (package inserts) and abstracts presented at the American Pain Society meetings (2003–2006) were also reviewed. Study Selection and Data Extraction Human studies evaluating the safety and efficacy of oral oxymorphone in pain management were considered; animal and non–English-language data were excluded. Data Synthesis Oral oxymorphone is a semisynthetic opioid agonist that is specific for the μ-opioid receptor and approved to treat both acute and chronic pain. Unlike other opioids, such as oxycodone, oxymorphone does not bind to the κ-opioid receptor. Due to extensive liver metabolism, oral oxymorphone is contraindicated in patients with moderate-to-severe hepatic impairment; however, no clinically significant CYP3A4, 2C9, or 2D6 mediated drug-drug interactions have been noted. Elderly patients may experience a 40% increase in plasma concentrations, while renally impaired patients may have a 57–65% increase in bioavailability. Food can increase the rate of absorption by as much as 50%, necessitating dosing either 1 hour before or 2 hours after a meal. Oxymorphone's primary adverse effects are similar to those of other opioids: nausea, vomiting, pruritus, pyrexia, and constipation. Conclusions Oxymorphone is an oral therapeutic option approved for the treatment of acute and chronic moderate-to-severe pain. Oxymorphone has a safety and efficacy profile similar to that of other commonly used pure opioids (morphine, oxycodone, hydromorphone). Like oxycodone and morphine, oxymorphone also has immediate-release and extended-re lease formulations. Since cost alone is not yet favorable for oxymorphone over oxycodone or morphine, further studies of comparative efficacy targeting potential advantages of oxymorphone over other opioids are necessary before considering it for addition to a formulary.

Interactions Between Antipsychotic and Antihypertensive Drugs

1995 ◽  
Vol 29 (6) ◽  
pp. 603-609 ◽  
Author(s):  
John S Markowitz ◽  
Barbara G Wells ◽  
William H Carson
Keyword(s):  
English Language ◽  
Antihypertensive Drugs ◽  
Case Reports ◽  
Data Extraction ◽  
Plasma Concentrations ◽  
Antihypertensive Agents ◽  
Background Information ◽  
Antipsychotic Therapy ◽  
Medline Search ◽  
Pertinent Data

Objective: To provide a comprehensive review of the pharmacokinetic and pharmacodynamic interactions between antipsychotics and antihypertensives and to provide recommendations for the selection of antihypertensives in patients receiving antipsychotic therapy. Data Sources: A MEDLINE search of the English-language literature was used to identify pertinent human and animal studies, reviews, and case reports. Study Selection: All available sources were reviewed. Data Extraction: Background information was obtained from comprehensive reviews. Individual case reports were assimilated, and pertinent data were extracted. Data Synthesis: Because hypertension is common in patients with psychiatric illness and antihypertensive agents are used for a multiplicity of indications, significant numbers of patients receive concurrent therapy with antihypertensives and antipsychotics. Many antipsychotics may block the antihypertensive efficacy of guanethidine and related drugs. The interaction between Clonidine and antipsychotics is defined less clearly. Limited data suggest possible additive hypotensive effects when chlorpromazine and methyldopa are given in combination. Increased plasma concentrations of thioridazine with a resultant increase in adverse effects have been reported when propranolol or pindolol are added to the regimen. A similar increase in chlorpromazine concentrations has been reported when propranolol was added. Although there are no reports documenting an interaction between a calcium-channel antagonist and an antipsychotic, the possible inhibition of oxidative metabolism of antipsychotics, additive calcium-blocking activity, and additive pharmacodynamic effects are theorized. Hypotension and postural syncope were reported in a patient given therapeutic dosages of chlorpromazine and Captopril, and in 2 patients when clozapine was added to enalapril therapy. Conclusions: No antipsychotic-antihypertensive combination is absolutely contraindicated, but no combination should be considered to be completely without risk. Antihypertensives with no centrally acting activity, such as diuretics, may be the least likely to result in adverse reactions. The combination of the beta-antagonists propranolol or pindolol with thioridazine or chlorpromazine should be avoided if possible. Scrupulous patient monitoring for attenuated or enhanced activity of either agent is essential whenever antipsychotics and antihypertensives are given concurrently.

Treatment Options for Rheumatoid Arthritis: Celecoxib, Leflunomide, Etanercept, and Infliximab

2000 ◽  
Vol 34 (6) ◽  
pp. 743-760 ◽  
Author(s):  
Brigitte T Luong ◽  
Barbara S Chong ◽  
Dionne M Lowder
Keyword(s):  
Rheumatoid Arthritis ◽  
English Language ◽  
Data Extraction ◽  
Treatment Options ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Antiinflammatory Drugs ◽  
Safety And Efficacy ◽  
Medline Search ◽  
Pertinent Data

OBJECTIVE: To review new pharmacologic agents approved for use in the management of rheumatoid arthritis (RA). DATA SOURCES: A MEDLINE search (1966–January 2000) was conducted to identify English-language literature available on the pharmacotherapy of RA, focusing on celecoxib, leflunomide, etanercept, and infliximab. These articles, relevant abstracts, and data provided by the manufacturers were used to collect pertinent data. STUDY SELECTION: All controlled and uncontrolled trials were reviewed. DATA EXTRACTION: Agents were reviewed with regard to mechanism of action, efficacy, drug interactions, pharmacokinetics, dosing, precautions/contraindications, adverse effects, and cost. DATA SYNTHESIS: Traditional pharmacologic treatments for RA have been limited by toxicity, loss of efficacy, or both. Increasing discoveries into the mechanisms of inflammation in RA have led to the development of new agents in hopes of addressing these limitations. With the development of celecoxib, a selective cyclooxygenase-2 inhibitor, the potential exists to minimize the gastrotoxicity associated with nonsteroidal antiinflammatory drugs. Leflunomide has been shown to be equal to or less efficacious than methotrexate, and may be beneficial as a second-line disease-modifying antirheumatic drug (DMARD). The biologic response modifiers, etanercept and infliximab, are alternatives that have shown benefit alone or in combination with methotrexate. However, they should be reserved for patients who fail to respond to DMARD therapy. Further studies should be conducted to evaluate the long-term safety and efficacy of these agents as well as their role in combination therapy. CONCLUSIONS: Celecoxib, leflunomide, etanercept, and infliximab are the newest agents approved for RA. Clinical trials have shown that these agents are beneficial in the treatment of RA; however, long-term safety and efficacy data are lacking.

Leukotriene-Receptor Antagonists and 5-Lipoxygenase Inhibitors in Asthma

1993 ◽  
Vol 27 (7-8) ◽  
pp. 898-903 ◽  
Author(s):  
Julie S. Larsen ◽  
Edward P. Acosta
Keyword(s):  
Clinical Trials ◽  
English Language ◽  
Data Extraction ◽  
Background Information ◽  
Receptor Antagonists ◽  
Lipoxygenase Inhibitors ◽  
Medline Search ◽  
Leukotriene Receptor Antagonists ◽  
Patient Tolerance ◽  
Leukotriene Receptor

OBJECTIVE: To familiarize readers with a potentially new class of compounds for treating asthma. Background information on leukotrienes is provided in addition to an indepth review of pertinent clinical trials. DATA SOURCES: Information was obtained from controlled clinical trials, abstracts, and review articles identified through a MEDLINE search of English-language articles. STUDY SELECTION: Emphasis was placed on early clinical trials that showed some benefit with these compounds as well as more recent studies using newer agents that produced more promising results. DATA EXTRACTION: Information regarding leukotriene biochemistry was extracted from basic science research and data from human studies were evaluated by the authors according to patient selection, study design, methodology, and therapeutic response. DATA SYNTHESIS: Leukotrienes have a pathophysiologic role in asthma. Two distinct but pharmacologically similar classes of leukotriene inhibitors are currently being clinically evaluated. These are leukotriene receptor antagonists and 5-lipoxygenase inhibitors. Early clinical trials with these agents yielded unfavorable results primarily because of lack of drug potency and selectivity, poor patient tolerance, and possibly the route of administration. Subsequent studies with more potent and selective agents have further implicated leukotrienes as biochemical mediators in asthma and, consequently, have shown promising clinical outcomes with respect to pulmonary function testing and patient tolerance. CONCLUSIONS: Advancements in the pathogenesis of asthma are beginning to define a role for the leukotrienes. Although more studies are needed to assess the efficacy of leukotriene inhibitors, recent clinical trials using leukotriene-receptor antagonists and 5-lipoxygenase inhibitors indicate a potential for the expansion of therapeutic regimens currently used in the treatment of asthma.

Providing Patients with Written Medication Information

1998 ◽  
Vol 32 (9) ◽  
pp. 962-969 ◽  
Author(s):  
Marcia L Buck
Keyword(s):  
English Language ◽  
Reading Skills ◽  
Healthcare Professionals ◽  
Data Extraction ◽  
Search Term ◽  
Care Providers ◽  
Specific Patient ◽  
Medline Search ◽  
Use Of Resources ◽  
Medication Information

OBJECTIVE: To review the literature and provide recommendations for the development and dissemination of written medication information to patients and their care providers. DATA SOURCES: A MEDLINE search (1966–1997) of the English-language literature was performed to identify articles pertaining to the development or use of written medication information. A search of the Internet was conducted by using Yahoo as the guide and “medication information” as the search term. Additional resources were obtained through texts, bibliographies, and catalogs from medical publishers. DATA EXTRACTION: Reports documenting the creation and use of written medication information systems were reviewed, as well as studies of readability and reading skills assessment. Examples of materials available for purchase by laypeople and healthcare providers were also examined. DATA SYNTHESIS: Current statistics support the widespread availability of written medication information for patients and care providers. The goal set forth by the Food and Drug Administration of having 75% of patients receive written information by the year 2000 appears achievable. However, there are still many issues to address. Content is not standardized, and materials are frequently written at reading levels higher than that of the average patient. The development and use of resources requiring only minimal reading skills and an increase in the availability of materials written in Spanish are needed. CONCLUSIONS: Written medication information provides a useful addition to counseling by healthcare professionals. A wide variety of prepared materials is available, as well as resources for those interested in developing tools for a specific patient, population, or setting. Healthcare professionals should be aware of the limitations of some resources. Content and readability must be appropriate for the intended audience for these tools to serve a useful role in patient education.

The Contact System

2002 ◽  
Vol 126 (11) ◽  
pp. 1382-1386 ◽  
Author(s):  
Craig S. Kitchens
Keyword(s):  
Antiphospholipid Syndrome ◽  
English Language ◽  
Case Reports ◽  
Data Extraction ◽  
Meta Analysis ◽  
Factor Xii ◽  
Activity Levels ◽  
Medline Search ◽  
Apparent Association

Abstract Objectives.—To review the literature for conditions, diseases, and disorders that affect activity of the contact factors, and further to review the literature for evidence that less than normal activity of any of the contact factors may be associated with thrombophilia. Data Sources.—MEDLINE search for English-language articles published from 1988 to 2001 and pertinent references contained therein, as well as search of references in recent relevant articles and reviews. Study Selection.—Relevant clinical and laboratory information was extracted from selected articles. Meta-analysis was not feasible because of heterogeneity of reports. Data Extraction and Synthesis.—Evidence for association of altered levels of the contact factors and thrombophilia was sought. A wide variety of disorders is associated with decreased activity of the contact factors; chief among these disorders are liver disease, hepatic immaturity of newborns, the antiphospholipid syndrome, and, for factor XII, being of Asian descent. These disorders are more common than homozygous deficiency. The few series and case reports of thrombophilic events in patients homozygous for deficiency of contact factors are not persuasive enough to support causality. The apparent association between levels consistent with heterozygosity (40%–60% of normal) of any of the contact factors (but especially factor XII) in persons with antiphospholipid antibodies appears to be due to falsely decreased in vitro activity levels of these factors, which are normal on antigenic testing. The apparent association with thrombosis is better explained by the antiphospholipid syndrome than by the modest reduction of the levels of contact factors. Conclusions.—Presently, it is not recommended to measure activity of contact factors during routine evaluation of patients who have suffered venous or arterial thromboembolism or acute coronary syndromes.

Isoniazid-Associated Psychosis: Case Report and Review of the Literature

1993 ◽  
Vol 27 (2) ◽  
pp. 167-170 ◽  
Author(s):  
Karen A. Pallone ◽  
Morton P. Goldman ◽  
Matthew A. Fuller
Keyword(s):  
Case Report ◽  
English Language ◽  
Case Reports ◽  
Data Extraction ◽  
Data Sources ◽  
Review Of The Literature ◽  
Data Synthesis ◽  
Medline Search ◽  
Study Selection ◽  
Language Literature

Objective To describe a case of isoniazid-associated psychosis and review the incidence of this adverse effect. Data Sources Information about the patient was obtained from the medical chart. A MEDLINE search of the English-language literature published from 1950 to 1992 was conducted and Index Medicus was manually searched for current information. Study Selection All case reports describing isoniazid-associated psychosis were reviewed. Data Extraction Studies were evaluated for the use of isoniazid, symptoms of psychosis, onset of symptoms, and dosage of isoniazid. Data Synthesis The case report is compared with others reported in the literature. The incidence of isoniazid-associated psychosis is rare. Conclusions The mechanism of isoniazid-associated psychosis is uncertain. It appears that isoniazid was associated with the psychosis evident in our patient and in the cases reviewed.

Therapeutic Equivalency of Low-Molecular-Weight Heparins

2002 ◽  
Vol 36 (6) ◽  
pp. 1042-1057 ◽  
Author(s):  
Gary M McCart ◽  
Steven R Kayser
Keyword(s):  
Molecular Weight ◽  
English Language ◽  
Data Extraction ◽  
Diagnostic Methods ◽  
Low Molecular Weight ◽  
Therapeutic Equivalence ◽  
Low Molecular Weight Heparins ◽  
Medline Search ◽  
Significant Difference ◽  
Therapeutic Equivalency

OBJECTIVE: To review the recent literature on the approved uses of enoxaparin, dalteparin, ardeparin, and tinzaparin and the evidence for therapeutic equivalence. DATA SOURCES: A MEDLINE search (1993–January 2001) was conducted to identify English-language literature available on enoxaparin, dalteparin, ardeparin, and tinzaparin. STUDY SELECTION: All controlled trials evaluating low-molecular-weight heparins (LMWHs) versus standard therapy powered to detect a significant difference were reviewed. DATA EXTRACTION: Agents were reviewed with regard to safety and efficacy. DATA SYNTHESIS: As a class, LMWHs have chemical, physical, and clinical similarities. LMWHs have greater bioavailability, longer half-lives, a more predictable pharmacologic response, possible improved safety, and similar or greater efficacy compared with unfractionated heparin (UFH). Because of this, enoxaparin, dalteparin, ardeparin, and tinzaparin are being considered as alternatives to UFH or warfarin, and there is potential for therapeutic interchange. Evaluation of clinical trials is limited because of differing diagnostic methods, drug administration times, dose equivalencies, and outcome measurements. CONCLUSIONS: Only 1 trial has evaluated 2 LMWHs in a direct comparison in the same study. There is insufficient evidence for determining the therapeutic equivalence of LMWHs.

Dexrazoxane: A New Cardioprotective Agent

1998 ◽  
Vol 14 (5) ◽  
pp. 182-190 ◽  
Author(s):  
Beverly D Abbott ◽  
Cindy M Ippoliti
Keyword(s):  
Supportive Care ◽  
English Language ◽  
Bolus Dose ◽  
Cardiac Tissue ◽  
Data Extraction ◽  
Data Synthesis ◽  
Medline Search ◽  
Search Terms ◽  
Study Selection ◽  
Clinically Significant

Objective: To review the literature discussing the use of dexrazoxane (e.g., Zinecard, ICRF-187) to prevent doxorubicin-induced cardiotoxicity. Data Sources: Pertinent English-language reports of studies in humans were retrieved from a MEDLINE search (January 1980-January 1997); search terms included chelating agents, razoxane, dexrazoxane, Zinecard, ICRF-187, ADR-529, and ICRF-159. Study Selection: Representative articles discussing the chemistry, pharmacology, pharmacokinetics, dosing, and administration of dexrazoxane and those discussing clinical trials were selected. Data Extraction: Data were extracted and analyzed if the information was relevant and consistent. Studies were selected for review in the text on the basis of study design and clinical end points. Data Synthesis: Dexrazoxane is a chemoprotective agent developed to prevent cardiac tissue toxicity. Dexrazoxane exerts a cardioprotective effect with some clinically significant toxicities; it may also interfere with the antitumor activity of doxorubicin. Until there are sufficient data to support its use in first-line supportive care therapy, dexrazoxane should be reserved for use in patients responding to doxorubicin-based chemotherapy but who have risk factors for cardiac toxicity or have received a cumulative doxorubicin bolus dose of 300 mg/m2. Conclusions: The management of doxorubicin-induced cardiotoxicity has led to the development of supportive care drugs that specifically counteract the dose-limiting toxicities. Dexrazoxane may not completely eliminate the concern about doxorubicin-induced cardiotoxicity, but it may open new avenues for continuing doxorubicin-based chemotherapy.

Use of Trans-Retinoic Acid in the Treatment of Acute Promyelocytic Leukemia

1993 ◽  
Vol 27 (2) ◽  
pp. 211-214 ◽  
Author(s):  
Alice M. Dulaney ◽  
Rebecca J. Murgatroyd
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
English Language ◽  
Retinoic Acid Receptor ◽  
Data Extraction ◽  
Promyelocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Extensive Discussion ◽  
Medline Search ◽  
Trans Retinoic Acid

Objective To discuss acute promyelocytic leukemia (APL) and review the literature concerning differentiation treatment of APL with trans-retinoic acid (t-RA). Data Sources English-language articles concerning APL or its treatment with t-RA were identified with a MEDLINE search. Study Selection All studies available at the time of article preparation, which addressed t-RA treatment in APL, were selected. Data Extraction Data extraction and assessment were performed subjectively by the authors. An extensive discussion of specific study details is included in the article. Data Synthesis APL is a unique subset of acute myelogenous leukemia and is typified by an accumulation of malignant promyelocytes in the bone marrow. Within the granulocyte cell cycle of a patient with APL, differentiation has been halted at the level of the promyelocyte, preventing formation of mature granulocytes. Upon treatment with traditional cytotoxic chemotherapy, complete remission rates of approximately 70 percent, with a five-year survival ranging from 25 to 40 percent have been achieved. In most patients with APL, a characteristic chromosomal t(15q+;17q-) translocation has been found, which may be responsible for the production of an aberrant retinoic acid receptor-alpha. Therefore, t-RA induction therapy has been investigated and has produced promising results. Administration of t-RA in dosages of 45–100 mg/m2/d has induced complete remissions. The apparent mechanism of t-RA is the induction of promyelocyte differentiation and maturation. The most common adverse effects noted have been dry skin, cheilitis, and headaches. Conclusions Upon consideration of the initial trials, t-RA appears to be a promising and unique treatment for APL.

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