Expert opinion on pharmacotherapy
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Expert Opin Pharmacother · Jan 2016
ReviewReversing neuromuscular blockade: inhibitors of the acetylcholinesterase versus the encapsulating agents sugammadex and calabadion.
Acetylcholinesterase inhibitors (neostigmine, edrophonium) and encapsulating agents (sugammadex and calabadion) can be used to reverse residual neuromuscular blockade (NMB). ⋯ The therapeutic range of acetylcholinesterase-inhibitors is narrow and effectiveness studies demonstrate clinicians don't use these unspecific reversal agents effectively to increase postoperative respiratory safety. The encapsulating drugs sugammadex and calabadion reverse all levels of NMB, and complete recovery of muscle strength can be achieved almost immediately after administration. For this reason encapsulating agents can be used as a solution for "cannot intubate cannot ventilate"- situations. Poor binding selectivity of encapsulating agents carries the risk of displacement of the NMBA by a competitively binding drug, which may lead to recurarization. In order to avoid side-effects, related to unspecific binding of endogenous proteins and drugs administered perioperatively it is prudent to titrate the dose of reversal agents to the minimal effective dose, depending on the depth of neuromuscular transmission block identified by neuromuscular transmission monitoring. Calabadions provide a diversified (increased binding selectivity) and expanded (reversal of benzylisoquinolines) spectrum of possible indications.
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Advanced breast cancer is incurable for most patients with limited therapeutic options. As such, there is a critical need for new and novel agents that lack cross-resistance and mitigate overlapping toxicities. ⋯ Etirinotecan pegol demonstrates anti-tumor activity and improved tolerability in patients with refractory metastatic breast cancer. As a novel topoisomerase I inhibitor in breast cancer, etirinotecan pegol holds great therapeutic potential, allowing the challenge of resistance in the advanced disease setting to be addressed.
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Expert Opin Pharmacother · Jan 2016
ReviewEfficacy of trebananib (AMG 386) in treating epithelial ovarian cancer.
Epithelial ovarian cancer (EOC) is the leading cause of death among gynecologic cancers. The majority of women are diagnosed with advanced stage disease. It is considered a chemosensitive cancer with a high initial response rate to first-line platinum and taxane-based chemotherapy. However, most patients with advanced EOC will relapse with subsequent resistance to conventional chemotherapy and ultimately succumb to their disease. Therefore, new therapeutic agents and strategies are desperately needed to improve the outcomes in patients with advanced EOC. ⋯ Targeting angiopoietin-Tie-2 pathway represents a promising alternative approach to tumor anti-angiogenesis with a distinct toxicity profile from the VEGF-dependent pathway inhibitors. However, there are still many questions to be answered regarding the optimal treatment schedules, maintenance regimens, duration of maintenance therapy, and the best combination strategy. Currently there is no reliable surrogate molecular, cellular, or genetic marker that would definitively predict response to anti-angiogenic therapy. Identification of certain relevant and predictive biomarkers in the future may optimize treatment's efficacy by distinguishing the subset group of patients with EOC that would derive the most benefit from existing antiangiogenic treatment regimens.
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Expert Opin Pharmacother · Jan 2016
Topical amitriptyline and ketamine for post-herpetic neuralgia and other forms of neuropathic pain.
Neuropathic pain (NP) has several therapeutic options but efficacy is limited and adverse effects occur, such that additional treatment options are needed. A topical formulation containing amitriptyline 4% and ketamine 2% (AmiKet) may provide such an option. ⋯ Topical AmiKet has the potential to be a first-line treatment option for PHN, and to be useful in other NP conditions. Furthermore, AmiKet has the potential to be an adjunct to systemic therapies, with the targeting of a peripheral compartment in addition to central sites of action representing a rational drug combination.