Emerging drugs in sepsis.

Expert Opin Emerg Drugs. 2010 Mar;15(1):41-52

Authors: Leone M, Textoris J, Michel F, Wiramus S, Martin C

IMPORTANCE OF THE FIELD: Sepsis remains a major cause of death in intensive care units. Despite an intense research, a new drug that is effective in reducing mortality in sepsis is still awaited. AREAS COVERED IN THIS REVIEW: The literature was analyzed with Pubmed() during the 2008 – 2009 period. If required, seminal articles published before 2008 were cited. Clinical trials focusing on ‘sepsis’ were first assessed. Next, relevant experimental data in this field were reported. WHAT THE READER WILL GAIN: The goal of the review is to determine the role for new licensed antibiotics, to give an insight into the conflict on adjuvant therapies and to disclose new experimental concepts. TAKE HOME MESSAGE: New licensed antibiotics will offer the opportunity to refine the treatment choices. Direct hemoperfusion using polymyxin B-immobilized fiber column may be an option in sepsis due to Gram-negative bacilli. Among non-antibiotic drugs, new ongoing studies will clarify the role of drotrecogin alfa (activated) and low dose hydrocortisone. The modulation of monocytic human leukocyte antigen-DR seems the most prominent treatment. The use of cardiovascular drugs requires well-conducted clinical trials. The regulation of high mobility group box 1, adenosine blockade or correction of the impaired energy production is still at the experimental level.

PMID: 20055688 [PubMed - indexed for MEDLINE]

[Read more →]

Emerging drugs for pulmonary hypertension.

Expert Opin Emerg Drugs. 2010 Mar;15(1):71-85

Authors: Girgis RE

IMPORTANCE OF THE FIELD: Pulmonary arterial hypertension (PAH) is a clinical syndrome characterized by structural narrowing of the small pulmonary arteries that often culminates in fatal right heart failure. AREAS COVERED IN THIS REVIEW: PubMed was searched for PAH and treatment. Data from scientific meetings and pharmaceutical websites are also included. There are currently eight FDA approved drugs for PAH that fall into one of three classes: prostacyclins, endothelin-receptor antagonists and PDE-5 inhibitors. All have important limitations and morbidity and mortality remain high. Several new agents with similar mechanisms of action are in clinical development. Multiple novel therapeutic targets are being explored. New applications for PAH therapies, such as pulmonary hypertension due to left heart and lung disease, are also being investigated. WHAT THE READER WILL GAIN: An understanding of currently available drugs and those in clinical development for pulmonary hypertension. TAKE HOME MESSAGE: Drugs targeting the pulmonary vasculature have been an extremely active area of basic and clinical research for the past 20 years and will continue to be so for the foreseeable future. Considerable progress has been made, and yet there continues to be a great unmet medical need for developing more efficacious therapies.

PMID: 20095920 [PubMed - indexed for MEDLINE]

[Read more →]

Erythropoietic stimulating agents.

Expert Opin Emerg Drugs. 2010 Mar;15(1):119-38

Authors: Testa U

IMPORTANCE OF THE FIELD: The synthesis of recombinant forms of erythropoietin, epoetin alpha, beta and darbepoetin alpha, has represented a major achievement in anemia therapy. AREAS COVERED IN THIS REVIEW: This review analyzes the therapeutic options of existing erythropoietic stimulating agents (ESAs) in patients with cancer, renal and heart failure anemia and shows the main features of new ESAs under development. Peer-reviewed scientific literature and abstracts published during the last 10 years were reviewed. WHAT THE READER WILL GAIN: Randomized clinical trials carried out in patients with anemia associated with chronic renal disease or malignancies have consistently demonstrated that ESAs increase hemoglobin levels, reduce blood transfusion requirements and improve quality of life. However, in spite of the positive effects, treatment with ESAs, particularly in oncologic patients, is associated with an increased mortality and cardiovascular complications. These observations imply the absolute need for using ESAs in the context of currently available guidelines. TAKE HOME MESSAGE: A razionalization in the clinical use of ESAs according to current guidelines is required to improve the benefits derived from therapy with these drugs. New ESAs are under development and their introduction in therapy could provide a significant improvement in anemia management.

PMID: 20158404 [PubMed - indexed for MEDLINE]

[Read more →]

Emerging drugs in chronic obstructive pulmonary disease.

Expert Opin Emerg Drugs. 2009 Mar;14(1):181-94

Authors: Seifart C, Vogelmeier C

Chronic obstructive pulmonary disease is one of the most relevant diseases with increasing incidence, morbidity and mortality. Although there have been therapeutic advances in the past decades, there is a lot of room for improvement. There are several new therapeutic strategies and a variety of novel drugs under development that are based on established concepts. These new drugs have the following targets: i) smoking; ii) airways obstruction; iii) inflammation; iv) protease-antiprotease imbalance; and v) regeneration of lung tissue. In the next few years, there will be bronchodilators with longer duration of action that may improve adherence. In addition, there will be fixed combinations of different bronchodilators and bronchodilators with corticosteroids, which may have a positive impact on parameters such as exacerbations, dyspnea and exercise capacity. Novel anti-inflammatory concepts that go beyond corticosteroids are in early phases of development and it remains to be seen how effective they are and what side effects they may carry.

PMID: 19265487 [PubMed - indexed for MEDLINE]

[Read more →]

Emerging diuretics for the treatment of heart failure.

Expert Opin Emerg Drugs. 2009 Mar;14(1):195-204

Authors: Sedghi Y, Gaddam KK, Ventura HO

Heart failure continues to be a major global concern. Despite greater understanding of the ‘maladaptive’ mechanisms that contribute to its development and progression, morbidity and mortality from heart failure remain high. Existing treatment modalities have been hampered by the development of electrolyte abnormalities, diuretic resistance and the cardiorenal syndrome. This review focuses on the pharmacological properties and clinical data of therapeutic agents under investigation that target vasopressin and adenosine receptors for the treatment of patients with heart failure.

PMID: 19196235 [PubMed - indexed for MEDLINE]

[Read more →]

Emerging drugs for chemotherapy-induced mucositis.

Expert Opin Emerg Drugs. 2008 Sep;13(3):511-22

Authors: Keefe DM, Sonis ST, Bowen JM

BACKGROUND: Chemotherapy-induced mucositis is an increasingly recognized problem in cancer management, preventing full doses of treatment being given, compromising cure rates and reducing quality of life. Symptoms include mouth pain and ulceration, esophagitis, abdominal pain, bloating, and diarrhea. It is associated with increased infections and occasional mortality, and its palliation is very expensive. The pathobiology of mucositis is complex, and agents that target mechanisms to prevent mucositis or accelerate healing are in high demand. OBJECTIVES: To review existing and potential treatments for chemotherapy-induced mucositis in the context of current knowledge of pathobiology. METHODS: We searched for mucositis of any region of the gastrointestinal tract using Medline, the Pharmaprojects database and listed patents. RESULTS/CONCLUSIONS: There are many agents in varying stages of development for chemotherapy-induced mucositis. The field is complicated by the question of whether treatments should be developed as drugs or as medical foods, and whether the burden of proof of efficacy and safety should be different.

PMID: 18764726 [PubMed - indexed for MEDLINE]

[Read more →]