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.

Drug-Induced Photosensitivity: A Clinical Review

1996 ◽  
Vol 12 (2) ◽  
pp. 52-57
Author(s):  
Stacey Beasley ◽  
Oscar E Araujo ◽  
Franklin P Flowers
Keyword(s):  
English Language ◽  
Data Extraction ◽  
Treatment Options ◽  
Coal Tar ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Hypoglycemic Agents ◽  
Thiazide Diuretics ◽  
Antiinflammatory Drugs ◽  
Drug Induced ◽  
Study Selection

Objective: To provide an overview of drug-induced phototoxic and photoallergy reactions, the mechanism involved, and the most common classes of drugs causing these reactions. Data Source: Pertinent English-language literature (1987–1993). Study Selection: Representative articles documenting mechanisms and types of drug-induced photosensitivity reactions, as well as treatment options. Data Extraction: Data were extracted only from articles that documented relevant and substantive information backed by clinical studies. Data Synthesis: Drug-induced photosensitivity can be acute or chronic. The chromophore that absorbs the radiation and activates the process of photosensitivity results in color within the longer ultraviolet wavelength. The primary classes of drugs causing phototoxic reactions include nonsteroidal antiinflammatory drugs, thiazide diuretics, tetracycline, and quinolone antibiotics, tricyclic antidepressants, and amiodarone. Those causing photoallergic reactions include antihistamines, thiazide diuretics, sulfonamides, griseofulvin, sulfonylurea hypoglycemic agents, benzocaine, and coal tar preparations. Conclusions: The importance of understanding the mechanism of photosensitivity is stressed as well as the difficulty in determining whether a phototoxic or photoallergic reaction has occurred. Established classes of each type of photosensitivity are identified and the importance of recognizing treatment options is emphasized. Patients prone to photosensitizing reactions should be advised concerning how to manage these problems.

Propofol for the long-term sedation of a critically ill patient

1998 ◽  
Vol 7 (1) ◽  
pp. 73-76 ◽  
Author(s):  
LJ Miller ◽  
R Wiles-Pfeifler
Keyword(s):  
Adverse Effects ◽  
English Language ◽  
Case Reports ◽  
Critically Ill Patient ◽  
Limited Data ◽  
Safety And Efficacy ◽  
Medline Search ◽  
Cardiovascular Depression ◽  
Language Literature

OBJECTIVE: To report a case in which propofol was used successfully in an intubated patient on a prolonged basis and to review the literature that discusses long-term infusions (> 7 days) of propofol. METHODS: Information was retrieved from a MEDLINE search of the English-language literature. Reports of clinical trials and case reports that compared the safety and efficacy of long-term propofol and midazolam were included in this review. Information about the study design and the efficacy and adverse effects of the drugs was collected, and the data were synthesized. RESULTS: Clinical reports indicate that a long-term infusion of propofol is comparable in safety and efficacy to a long-term infusion of midazolam. The distinct adverse-effect profile of long-term use of propofol, including hypertriglyceridemia, was evaluated and reported as significant. CONCLUSION: The limited data available suggest that long-term infusion of propofol is a practical alternative to use of standard agents for sedation of intubated patients. Adverse effects such as cardiovascular depression, respiratory depression, and hypertriglyceridemia may limit the routine use of propofol.

Topical Aminophylline: Is it Safe and Effective in Causing Regional Fat Loss?

1997 ◽  
Vol 13 (2) ◽  
pp. 80-83
Author(s):  
Lisa M Tong ◽  
Kristin R Gericke
Keyword(s):  
Adverse Effects ◽  
English Language ◽  
Data Extraction ◽  
Treatment Options ◽  
Local Concentration ◽  
Drug Induced ◽  
Fat Loss ◽  
Study Selection ◽  
Data Source

Objective: To provide a better understanding of the efficacy and possible adverse effects of topical aminophylline in causing regional fat loss. Data Source: Pertinent English-language literature (1958–1995). Study Selection: Representative articles documenting mechanisms of action and types of drug-induced reactions, as well as treatment options. Data Extraction: Data were extracted only from articles that documented relevant and substantive information backed by clinical studies. Data Synthesis: Topical aminophylline 2% thigh cream has been introduced as a method of treating cellulite, or dimpled thighs and buttocks. The proposed method of action is by increasing local concentration, thereby stimulating lipolysis. Data from two small clinical trials showed that the cream reduced thigh girth and had no known adverse effects. However, adverse dermatologic effects caused by aminophylline have been reported in the past. Conclusions: Topical aminophylline cream appears to be a reasonable option for regional reduction of thigh girth for some people and has not shown any adverse effects. Nevertheless, larger, long-term studies need to be done.

Pathophysiology and First-Line Treatment of Osteoarthritis

2002 ◽  
Vol 36 (4) ◽  
pp. 679-686 ◽  
Author(s):  
Jesse H Hogue ◽  
Tracey L Mersfelder
Keyword(s):  
Data Extraction ◽  
Treatment Options ◽  
Primary Treatment ◽  
Data Sources ◽  
Treatment Modalities ◽  
Comparable Efficacy ◽  
Antiinflammatory Drugs ◽  
Medline Search ◽  
Cox 2 ◽  
Cox 2 Inhibitors

OBJECTIVE: To review the pathophysiology of osteoarthritis (OA) and the various treatment modalities, focusing specifically on acetaminophen (APAP), nonsteroidal antiinflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) inhibitors as the primary treatment options. DATA SOURCES: Primary literature and tertiary references were identified by a MEDLINE search (1966–March 2001) and through other secondary sources. STUDY SELECTION AND DATA EXTRACTION: After evaluating the articles and references identified from the data sources, all the information that was judged relevant by the reviewers was included in the review article. DATA SYNTHESIS: OA is the most common joint disorder worldwide. Current research suggests that factors such as inflammation and changes in subchondral bone may play a larger role in the pathophysiology than previously thought. With this research and the development of COX-2 inhibitors, selecting the medication of choice for OA has become difficult. CONCLUSIONS: More research needs to be done before the pathophysiology of OA can be clearly determined. In the meantime, treatment should be based on clinical data and patient response. Studies have shown that APAP and NSAIDs have comparable efficacy, as do traditional NSAIDs and COX-2 inhibitors. APAP is associated with fewer toxicities than are the traditional NSAIDs. Due to their mechanism of action, the new COX-2 inhibitors should result in fewer adverse effects compared with traditional NSAIDs, but evidence from clinical trials has not been conclusive. Therefore, APAP should still be considered the drug of choice for OA.

Glucosamine

1998 ◽  
Vol 32 (5) ◽  
pp. 574-579 ◽  
Author(s):  
Teresa Susanne Barclay ◽  
Candy Tsourounis ◽  
Gary M McCart
Keyword(s):  
Adverse Effects ◽  
Data Extraction ◽  
Critical Evaluation ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Control Group ◽  
Antiinflammatory Drugs ◽  
Skin Reactions ◽  
Medline Search ◽  
Degenerative Process ◽  
Gastrointestinal Problems

OBJECTIVE: To review the pharmacology and pharmacokinetics of glucosamine and critically evaluate currently available literature regarding its safety and efficacy. DATA SOURCE: A MEDLINE search was conducted between January 1965 and May 1997. Key words used in the search were osteoarthritis, osteoarthrosis, gonarthrosis, and glucosamine. In addition, references cited in articles obtained from the MEDLINE search were reviewed for additional literature. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for inclusion in the review. Articles were excluded from critical evaluation for lack of randomization, lack of a control group, 30 or fewer study participants, inconsistent treatment regimen, incomplete dosing information, or incomplete reporting of results. DATA SYNTHESIS: Osteoarthritis affects approximately 12% of the US population; the incidence increases with increasing age. Currently used pharmacologic treatments, including acetaminophen and nonsteroidal antiinflammatory drugs, do not slow or reverse the degenerative process in osteoarthritis. Glucosamine has recently received a great deal of attention from the public as a potential treatment of osteoarthritis, prompting healthcare professionals to investigate its clinical usefulness and potential for adverse effects. The drug has been proposed to stop and possibly reverse the degenerative process in osteoarthritis. Following absorption of an oral dose, glucosamine is incorporated into plasma proteins during first-pass metabolism, resulting in 26% bioavailability. Unbound glucosamine is concentrated in the articular cartilage. Each of the three critically evaluated studies reported a decrease in the symptoms of osteoarthritis (e.g., decreased Lequesne index, decreased pain severity, increased range of motion) for the glucosamine group, which was greater than that obtained in the control group. Flaws in study design, however, prevent the use of these results in modifying current clinical practice. Reported short-term adverse effects include mild gastrointestinal problems, drowsiness, skin reactions, and headache. CONCLUSIONS: Improvement in the symptoms of osteoarthritis associated with the use of glucosamine has been observed in clinical trials; however, those trials have flaws in design and data analysis. Further research needs to be conducted before glucosamine can be recommended as a treatment for osteoarthritis.

Nabumetone: A “Nonacidic” Nonsteroidal Antiinflammatory Drug

1993 ◽  
Vol 27 (4) ◽  
pp. 456-463 ◽  
Author(s):  
Stephen L. Dahl
Keyword(s):  
Soft Tissue ◽  
Adverse Effects ◽  
English Language ◽  
Human Subjects ◽  
Data Extraction ◽  
Soft Tissue Injuries ◽  
Antiinflammatory Drugs ◽  
Double Blind ◽  
Medline Search ◽  
Tissue Injuries

OBJECTIVE: To review the pharmacology, pharmacokinetic disposition, dosage recommendations, adverse effects, drug interactions, and efficacy of nabumetone in patients with selected rheumatic disorders and soft-tissue injuries. DATA SOURCES: Data from scientific literature were extracted, evaluated, and summarized for presentation. A MEDLINE search was conducted using the following indexing terms: antiinflammatory agents, nonsteroidal, nabumetone, rheumatoid arthritis (RA), and osteoarthritis (OA). Studies evaluating nabumetone reported in articles, abstracts, or proceedings involving human subjects were considered for inclusion. STUDY SELECTION: Special consideration was given to clinical studies using double-blind, randomized, parallel, controlled designs. Studies comparing the effectiveness and safety of nabumetone with placebo and other nonsteroidal antiinflammatory drugs (NSAIDs) were included. DATA EXTRACTION: Data from human studies published in the English language were evaluated. Trials were assessed according to study design, sample size, and description of outcomes. DATA SYNTHESIS: Nabumetone is a nonacidic prodrug that is metabolized to an active nonsteroidal antiinflammatory moiety, 6-methoxy-2-naphthylacetic acid (6-MNA). 6-MNA is a structural analog of naproxen. Like naproxen and other NSAIDs, 6-MNA possesses analgesic, antipyretic, and antiinflammatory activity. 6-MNA has a prolonged elimination half-life, ranging from 17 to 74 hours, which allows for once-daily dosing. The efficacy of nabumetone for treating symptoms of RA and OA has been established in controlled clinical trials. Nabumetone also has been studied in ankylosing spondylitis and soft-tissue injuries. Adverse effects associated with nabumetone are similar to those associated with other NSAIDs. Gastrointestinal reactions occur most frequently in the form of abdominal pain or indigestion, nausea, or vomiting. Central nervous system adverse effects occur less frequently, and are followed in order of occurrence by rashes. CONCLUSIONS: Nabumetone is a prodrug metabolized to an active metabolite structurally related to naproxen. Studies have demonstrated the efficacy of nabumetone, but no advantages over the many other NSAIDs now available.

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.

Update on the Pharmacotherapy of Obesity

2007 ◽  
Vol 41 (9) ◽  
pp. 1505-1517 ◽  
Author(s):  
Jennifer Cerulli ◽  
Ben M Lomaestro ◽  
Margaret Malone
Keyword(s):  
Food Intake ◽  
Adverse Events ◽  
English Literature ◽  
Treatment Options ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Medline Search ◽  
Regulate Food Intake

Objective: To review recent developments in the pharmacotherapy of obesity, including the agents currently approved for use in the management of obesity and those under development. Data Sources: A MEDLINE search from January 1990 to July 1997 was conducted to identify English literature available on the pharmacotherapy of obesity. The search was supplemented by a review of the bibliographies of identified literature. Study Selection: All controlled and uncontrolled trials were reviewed. When available, double-blind, placebo-controlled trials were used preferentially. Data Extraction: Agents were reviewed with regard to mechanism of action, clinical trial data regarding efficacy, adverse effects, pharmacokinetics, drug interactions, and contraindications where information was available. Study design, selected population, results, and adverse effect information were included. Data Synthesis: The anorexiants currently available or under development for the management of obesity regulate food intake and satiety via the adrenergic and/or serotonergic pathways. Clinical trials have shown a 10–15% weight loss can typically be anticipated; however, little long-term safety and efficacy data are available. Adverse events tend to be mild and self-limiting, but serious adverse events can occur. Treatment options under development include thermogenic agents, digestive inhibitors, and analogs and antagonists of hormones that regulate food intake and satiety. Conclusions: Several mechanisms to control weight are currently under investigation for the management of obesity. Since obesity is a chronic condition, further studies should be conducted to evaluate the long-term safety and efficacy of these agents and the role of combination therapy using different modalities.

Impact of Nonsteroidal Antiinflammatory Drugs on the Cardioprotective Effects of Aspirin

2005 ◽  
Vol 39 (6) ◽  
pp. 1073-1079 ◽  
Author(s):  
Shelby L Corman ◽  
Bethany A Fedutes ◽  
Nicole T Ansani
Keyword(s):  
Myocardial Infarction ◽  
Clinical Outcomes ◽  
Observational Studies ◽  
Human Subjects ◽  
Data Extraction ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Antiinflammatory Drugs ◽  
Pharmacodynamic Interaction ◽  
Medline Search ◽  
Cardioprotective Effects

OBJECTIVE: To examine the evidence of a pharmacodynamic interaction between aspirin and nonsteroidal antiinflammatory drugs (NSAIDs); specifically, to determine whether a deleterious relationship exists with respect to the cardioprotective effects of aspirin. DATA SOURCES: Primary articles were identified by a MEDLINE search (1966—May 2004). Search terms included aspirin, nonsteroidal antiinflammatory drug, drug interaction, mortality, myocardial infarction, and stroke. STUDY SELECTION AND DATA EXTRACTION: All prospective and retrospective studies conducted in human subjects and investigating the potential interaction between aspirin and NSAIDs were included. DATA SYNTHESIS: Several controlled pharmacodynamic studies indicate that the sustained inhibition of cyclooxygenase activity by aspirin is blunted in the presence of some NSAIDs. While these data are fairly consistent, they are limited in that they rely on surrogate markers and not clinical outcomes. Observational studies have shown conflicting results regarding the effect of combination NSAID and aspirin therapy on mortality risk and incidence of myocardial infarction. CONCLUSIONS: Pharmacodynamic data indicating an interaction between aspirin and NSAIDs have not translated to a consistent clinical effect in observational studies. In the absence of a randomized, controlled, clinical outcomes study, there is insufficient evidence to dictate a change in therapy.

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