Advances and issues in the pharmacotherapy of rheumatoid arthritis

Rheumatoid arthritis (RA) is an unremitting and progressive disease despite the use of second–line drugs in the majority of patients. In addition, a shortened life–span directly attributable to RA is now recognized. The additions of methotrexate and sulfasalazine to the therapeutic armamentarium represent important treatment advances during the past decade. To improve the effectiveness of second–line drug therapy, earlier intervention and use of these newer drugs in combination with older second–line drugs is being advocated. Several proposed strategies for intervening earlier, combining second–line drugs, and/or improving patient selection for second–line drug therapy are reviewed. Systematic evaluation of these strategies is needed. Controlled studies to date have not demonstrated combining secondline drugs is superior to using individual secondline agents. Future advances in optimizing patient outcomes with these drugs will require systematic screening for potentially superior treatment strategies followed by supportive proof of effectiveness in the form of large–scale studies.     

Advances in pharmacotherapy: recent developments in the treatment of epilepsy

Epilepsy is a disorder of the central nervous system in which the clinical symptoms are recurrent seizures. An increased understanding of the underlying mechanism of seizures and more definitive diagnostic procedures have improved the care of the patient with epilepsy. An improved classification of various seizure types, including specific epilepsy syndromes has helped optimize use of the standard antiepileptic drugs. Research on the mechanism of seizures has led to new antiepileptic drugs. More definitive diagnostic procedures have led to more accurate identification of patients likely to benefit from epilepsy surgery. This review focuses on these areas.     

Rational-emotive therapy plus pharmacotherapy versus pharmacotherapy alone in the treatment of high cognitive dysfunction depression

A pilot study was conducted with 20 unipolar depressed outpatients with high levels of cognitive dysfunction. They were treated with either Lofepramine or Lofepramine plus rational-emotive therapy (RET) for 24 weeks. Previous studies of combined treatment versus pharmacotherapy have been criticized for selecting untypical clinical cases and for delivery of suboptimal pharmacotherapy. The present study was designed to address these issues as a preliminary to conducting a larger trial. The treatment protocol permitted a maximum of 30 RET sessions and 280 mg/day of Lofepramine. Ellis's rational-emotive therapy was used. There were significantly more responders in the combined-treatment group than in the pharmacotherapy group. At treatment termination, combined treatment similarly produced significantly greater changes in both depression measures and improvement in social adjustment. Furthermore, at termination in the combined-treatment group there were significantly more improvers and remitters on the Hamilton Depression Scale and on the Global Index of Improvement and more improvers on the target problems ratings. The overall attrition rate in this study was low at 5%. The population studied was more severely depressed and dysfunctional than populations previously included in cognitive therapy/pharmacotherapy trials. Despite utilizing a more severely depressed and dysfunctional sample than previous trials, combined treatment was found to produce more improvement than pharmacotherapy alone.     

Critical care pharmacotherapy: issues and approaches

Critically ill patients are a unique group with potentially altered pharmacokinetic and pharmacodynamic characteristics. The provision of optimal care to these patients is best accomplished via an intensivist-led multidisciplinary team. Included on this team should be a pharmacist specifically trained in critical care. The presence of a critical care pharmacist has been documented to not only decrease the cost of drug use in this setting but to improve the quality of care as well. Further investigations should focus on the impact of these interventions on outcomes. These will include pharmacoeconomic outcomes as well as their impact on other parts of the healthcare system in order to avoid cost shifting and improve morbidity and mortality.     

A review of combined psychotherapy and pharmacotherapy in the treatment of depression

The effectiveness of combined psychotherapy and pharmacotherapy for depression is a clinical issue of increasing importance. Using a box score approach, the authors review the 17 available studies in the literature, provide a methodological critique, summarize results, and suggest directions for further research and for clinical practice. Overall, given methodological limitations in the existing literature, it appears that combined treatment is no less effective than psychotherapy or pharmacotherapy alone and may have specific advantages for subpopulations of depressed patients.     

Recent advances in neonatal pharmacotherapy

OBJECTIVE: To provide commentary and reviews and brief discussions in controversial or innovative recent advances in neonatal pharmacotherapy. To discuss cutting edge drug delivery systems that may become useful in neonatal drug delivery in the future. DATA SOURCES: Articles were identified through searches of MEDLINE (1990-October 2005), key articles in the authors' files, and in some cases, through data generated and/or published by the author of a particular topic. DATA SELECTION: Article selection and relevance to the topics under discussion was determined by individual authors. DATA SYNTHESIS: Therapeutic strategies addressed in this review include the use of hematopoietic growth factors including a simulated amniotic fluid preparation containing these growth factors for neonates with selected gastrointestinal problems, erythropoietin for neuroprotection following perinatal asphyxia, drug therapy advances in treatment of patent ductus arteriosus (PDA), evaluation of advances in transdermal drug delivery, and its potential application to neonates and advances in the treatment of persistent pulmonary hypertension (PPHN) of the newborn. CONCLUSIONS: Despite being over 30 years old, the practice of neonatology is as much of an art as a science. Advances in the basic science research have improved our understanding of use of pharmacologic agents in the premature and full-term neonate including drug disposition pathways. Expanding our knowledge on issues such as physiology of hematopoietic factors, the pharmacologic responses of conditions such as PDA and PPHN, and newer technologies for drug administration, as well as other pharmacologic responses in the neonate are vital in the development of safe and efficacious treatments for neonates. Many questions remain unanswered, and every clinician must make an effort to contribute to the knowledge and understanding of pharmacotherapy in this patient population.     

Issues and advances in the pharmacotherapy of asthma.

Evidence is accumulating that inflammation of the airways is directly responsible for the increased bronchial hyperresponsiveness (BHR) and lung function obstruction in asthma. Bronchoprovocation with non-specific, direct bronchoconstrictors (methacholine and/or histamine) can be used as an indirect measurement of inflammation. Thus bronchoprovocation is a useful method for evaluating the long-term benefits of various therapies in asthma. The focus of asthma therapy research is now on the development of anti-inflammatory agents. Inhaled corticosteroids are currently the most potent anti-inflammatory agents in the treatment of asthma and so are generally the most effective in reducing BHR with long-term use. Non-corticosteroid anti-inflammatory agents that are currently available are reviewed. Recent studies have suggested that regular use of inhaled bronchodilators may actually be detrimental in asthma. At this time the data is still inconclusive but certainly warrants the attention of practitioners and requires further research, particularly in relation to the long-acting beta 2-agonists, formoterol and salmeterol.     

Assessment and pharmacotherapy of depression

Depressive disorders are experienced by a significant number of patients with cancer, with reported rates of 0%-58% (Massie, 2004). Numerous studies have demonstrated that depression in patients with cancer is underdiagnosed and inadequately treated as a result of a number of factors (Schwartz, Lander, & Chochinov, 2002). Although more severe or complex situations involving depression or other mental illness necessitate specialist referral, sometimes professionals treating patients with cancer may find the need to initiate treatment. Thus, clinicians need to be aware of basic principles related to the assessment and treatment of depression.     

Advances in paediatric pharmacotherapy.

Marked differences in body composition and organ function development have been demonstrated among neonates, infants, and children versus adults. Specific dosage guidelines for the paediatric population, however, are still not available for the majority of marketed drugs. Much needs to be learned about the pharmacokinetics, pharmacodynamics, comparative efficacy and safety of drugs in infants and children. Recent developments in paediatric therapeutics include the availability of several new antibiotics for the treatment of infections including, streptococcal pharyngitis, otitis media, bacterial meningitis, herpes encephalitis, neonatal herpes, and AIDS. Corticosteroids and intravenous immunoglobulin have become important adjunctive treatments for certain infections. A variety of drugs are available to treat asthma but the mortality due to this disease is still increasing. The identification of a gene defect in patients with cystic fibrosis could lead to more effective treatment in the future. Ondansetron, marketed for use in adults only, shows promise as a more effective and safer antiemetic in children receiving cancer chemotherapy. Numerous drugs are not available in suitable dosage forms for paediatric use and extemporaneous formulations are required. Documentation on the stability of the reformulated drugs is therefore needed. Studies have shown that the methods used for intravenous delivery can influence the serum concentrations of drugs in infants and children. Large numbers of children could be saved worldwide solely with improved vaccination and control of diarrhoea. Despite this, it is encouraging to witness the continued advances being made in paediatric pharmacotherapy.     

Advances in pharmacotherapy: Treatment of hypertensive crisis

A hypertensive crisis can be caused by many factors. Frequently, the mechanism involved is complex and highly variable among patients. Without drug therapy, this condition is associated with very high mortality and morbidity. There are a number of oral and intravenous hypotensive agents available, which can effectively control blood pressure in a hypertensive crisis. The relative advantages and disadvantages of each treatment option is discussed.     

Pain: advances and issues in critical care

The milieu of the critical care unit is stressful for both the patient and health care professionals. As such, it has the potential to increase pain perception in patients, and decrease the nurse's awareness of pain relief needs of the patient. Several physical and pharmacologic methods of pain relief were discussed in this article. Nontechnologic analgesia such as hypnosis and relaxation were introduced as adjuncts or alternatives to more familiar methods of pain relief. Although critically ill patients are not always able to express their discomfort, it is the responsibility of the nurse to recognize the potential for pain, and plan treatment accordingly. This article suggests several strategies for dealing with pain in critically ill patients.     

Advances in the pharmacotherapy of cystic fibrosis.

The quality of life and life-span of cystic fibrosis patients have been improved substantially in the last 20 or 30 years. This has been accomplished largely through improved early diagnosis and advances in traditional pharmacotherapy which mainly consists of antibiotic therapy. In the past few years, the basic cellular defect of cystic fibrosis, as well as the gene determining the disease, have been described. These milestones in the quest for knowledge about the disease open the door for other innovative forms of therapy. While corrective gene therapy may be the ultimate result of advances made based upon this new knowledge, we will probably see earlier breakthroughs in the form of immune reaction inhibition and correction of ion flux disturbances. Each of these present and future forms of therapy is explored in this paper.     

Recent advances in antifungal pharmacotherapy for invasive fungal infections

Invasive fungal infections carry significant morbidity and mortality. Candida species have become one of the most frequent causes of bloodstream infections, and infections caused by molds such as Aspergillus are becoming more frequent in immunocompromised patients. As this population grows, more invasive fungal infections can be anticipated. In the past, treatment options have been limited for many of these infections due to toxicity and efficacy concerns with the available antifungals. Fortunately, the past few years have brought exciting developments in antifungal pharmacotherapy. Lipid-based formulations of amphotericin B were introduced in the 1990s to attenuate adverse effects caused by amphotericin B deoxycholate (Fungizone, Bristol-Myers Squibb). Most recently, the echinocandins have been added to our antifungal regimen with the introduction of caspofungin (Cancidas, Merck and Co.) and voriconazole (Vfend, Pfizer), a new triazole, has come to market. The introduction of the echinocandins has invigorated the discussion about combination antifungal therapy. Evidence-based studies using these new agents are accumulating, and they are assuming important roles in the pharmacotherapy of invasive fungal infections in seriously ill and complex patients.