Expert opinion on pharmacotherapy
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Expert Opin Pharmacother · Apr 2013
ReviewSeptic shock: new pharmacotherapy options or better trial design?
Over the last two decades, many of the mechanisms underlying the pathophysiology of sepsis have been uncovered, but this has not led to the development of effective therapies for sepsis. Despite improvements in the general care of critically ill patients in recent years, mortality rates for patients with severe sepsis and septic shock remain high at 30 to 50% and there is an urgent need to develop new, effective therapeutic strategies. ⋯ Many reasons have been put forward over the years to explain the many negative results from trials of immunomodulatory therapies. Future studies need to be designed to specifically target patients who can benefit from the intervention being studied rather than at the sepsis population in general. The timing of administration of potential therapies also needs to be taken more into consideration.
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The discovery of somatic mutations in melanoma has advanced our knowledge of the biology of the disease. The mutations, such as those in NRAS, BRAF, GNAQ and GNA11, promote the growth of melanoma cells in most part through the mitogen-activated protein kinase (MAPK) pathway. Understanding the molecular pathways of some of these mutations has resulted in the successful development of selective BRAF inhibitors. Yet, a cure for advanced melanoma is far from reality. Targeting MAPK/ERK kinase (MEK), an essential intermediary kinase protein within the MAPK pathway, may be a promising way to treat patients with BRAF or other genomic mutation. ⋯ Studies have demonstrated the activity of trametinib in BRAF-mutant melanoma, suggesting that it could be a very reasonable alternative to BRAF inhibitors for these patients. Current clinical investigations have shown great promise with the combination of trametinib and dabrafenib in patients with BRAF-mutant melanoma; a number of clinical trials of trametinib in combination with other targeted drugs are underway.
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Expert Opin Pharmacother · Apr 2013
ReviewAn update on palonosetron hydrochloride for the treatment of radio/chemotherapy-induced nausea and vomiting.
Nausea and vomiting are well recognized in different clinical situations, suggesting that no single mechanism is likely to be responsible for their production. Chemotherapy-induced nausea and vomiting (CINV) can have a negative impact on quality of life and this may lead to a refusal of curative therapy or to a decline in palliative benefits offered by cytotoxic treatment. Palonosetron is a new agent in the class of 5-HT3 receptor antagonists (5-HT3RAs), and differs from the other agents by its higher receptor-binding affinity and longer half-life. These pharmacological properties have resulted in improved antiemetic activity in clinical trials, particularly in the treatment of delayed CINV following moderate emetogenic chemotherapy (MEC). ⋯ Palonosetron was the only serotonin receptor antagonist approved for prevention of delayed CINV caused by MEC and its use was incorporated in guideline recommendations. To date, several treatment settings such as multiple day chemotherapy require further studies to improve emesis related to therapy.
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Expert Opin Pharmacother · Apr 2013
Aclidinium bromide/formoterol fumarate fixed-dose combination for the treatment of chronic obstructive pulmonary disease.
Combining a long-acting β(2)-agonist (LABA) and a long-acting antimuscarinic agent (LAMA) is potentially a good pharmacological approach to improve clinical results in stable moderate chronic obstructive pulmonary disease (COPD) patients when symptoms are not adequately controlled with tiotropium monotherapy. Consequently, there is a strong interest in developing a LABA/LAMA fixed-dose combination therapy in an attempt to simplify the treatment. ⋯ Studies assessing the impact of aclidinium bromide/formoterol fumarate fixed-dose combination on COPD exacerbations, exercise capacity and hospitalisations are clearly needed to better detect its potential effects of disease modification in COPD. Moreover, it seems pragmatic to proceed with its introduction in the market at a highly competitive price.