Expert review of clinical pharmacology
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The immune system plays a vital role in regulating tumor growth, and the oncology community has witnessed an exciting resurgence in clinical research to develop effective immunotherapeutic strategies. The utility of these strategies in advanced melanoma has been at the forefront of these developments. ⋯ Pembrolizumab is a humanized IgG4 anti-PD-1 antibody that exerts its anti-tumor effect through blocking the interaction of the immune inhibitory molecule PD-1 with its ligands. Its effect has been most convincingly demonstrated in the setting of advanced melanoma, with growing evidence of clinical responses across a broad spectrum of other solid and hematological malignancies.
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Expert Rev Clin Pharmacol · Jan 2015
ReviewAfamelanotide (CUV1647) in dermal phototoxicity of erythropoietic protoporphyria.
The application of afamelanotide, an α-melanocyte stimulating hormone agonistic analogue to protoporphyria, a disease with absolute sunlight-intolerance is discussed. The clinics, genetics and existing therapies of protoporphyria are described. The physiological receptor-mediated intracellular signaling of α-melanocyte stimulating hormone and effects of receptor variants are outlined. ⋯ The trial results were significant, although the effects were not very large in absolute terms, and the risk-safety profile is favorable today. Based on the high compliance rate and the excellent consistency in clinical effectiveness during six years of compassionate use program in Switzerland, we expect afamelanotide and analogues to become a prospective therapeutic tool. Moreover, we hope that dosage forms suitable for children will be developed in future, as children and adolescents suffer most in protoporphyria.
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Expert Rev Clin Pharmacol · Nov 2014
ReviewEffect of sedative-hypnotics, anesthetics and analgesics on sleep architecture in obstructive sleep apnea.
The perioperative care of obstructive sleep apnea (OSA) patients is currently receiving much attention due to an increased risk for complications. It is established that postoperative changes in sleep architecture occur and this may have pathophysiological implications for OSA patients. Upper airway muscle activity decreases during rapid eye movement sleep (REMS). ⋯ This article critically reviewed the literature relevant to preoperative screening for OSA, prevalence of OSA in surgical populations and changes in postoperative sleep architecture relevant to OSA patients. In particular, we addressed three questions in regard to the effects of sedative-hypnotics, anesthetics and analgesics on sleep architecture, the underlying mechanisms and the relevance to OSA. Indeed, these classes of drugs alter sleep architecture, which likely significantly contributes to abnormal postoperative sleep architecture, exacerbation of OSA and postoperative complications.
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Expert Rev Clin Pharmacol · Sep 2014
Editorial ReviewTreating chronic pain: the need for non-opioid options.
Chronic pain is a prevalent problem that exacts a significant toll on society. The medical system has responded to this issue by implementing pain management services centered on opioid pharmacotherapy. However, for many chronic pain patients, the analgesic efficacy of long-term opioids is limited. ⋯ As such, non-opioid treatment options are needed. This article first provides a selective review of cognitive, affective, and psychophysiological mechanisms implicated in chronic pain to be targeted by novel non-opioid treatments. Next, it briefly details one such treatment approach, Mindfulness-Oriented Recovery Enhancement, and describes evidence suggesting that this intervention can disrupt the risk chain linking chronic pain to prescription opioid misuse.
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Ulcerative colitis is a chronic inflammatory disease of the large intestine that often develops in the young. A few new treatment options have become available in the past decade, but management of a large proportion of patients still remains challenging because of side effects, unresponsiveness and cost. ⋯ In this article we discuss molecules that block leukocyte trafficking to inflamed bowel that have been tested in ulcerative colitis. Because of favourable efficacy and safety data, we will review the development, pharmacology and clinical data of vedolizumab, a gut-selective α4β7 antibody, in depth.