Expert opinion on pharmacotherapy
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Expert Opin Pharmacother · Aug 2014
ReviewDronabinol and chronic pain: importance of mechanistic considerations.
Although medicinal cannabis has been used for many centuries, the therapeutic potential of delta-9-tetrahydrocannabinol (Δ9-THC; international non-proprietary name = dronabinol) in current pain management remains unclear. Several pharmaceutical products with defined natural or synthesized Δ9-THC content have been developed, resulting in increasing numbers of clinical trials investigating the analgesic efficacy of dronabinol in various pain conditions. Different underlying pain mechanisms, including sensitization of nociceptive sensory pathways and alterations in cognitive and autonomic processing, might explain the varying analgesic effects of dronabinol in chronic pain states. ⋯ We suggest a mechanism-based approach beyond measurement of subjective pain relief to evaluate the therapeutic potential of dronabinol in chronic pain management. Development of objective mechanistic diagnostic biomarkers reflecting altered sensory and cognitive processing in the brain is essential to evaluate dronabinol induced analgesia, and to permit identification of responders and/or non-responders to dronabinol treatment.
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Expert Opin Pharmacother · Aug 2014
EditorialEnd-stage renal disease with atrial fibrillation: uncharted territory in the modern world of anticoagulants.
End-stage renal disease (ESRD) and atrial fibrillation are increasingly common concurrent findings among many patients. Coexisting ESRD and atrial fibrillation can further exacerbate each disease process; thus, evidence-based medicine protocols are needed for the treatment of patients with both ESRD and new-onset atrial fibrillation to clarify the appropriate anticoagulant management of such patients. ⋯ Unlike many disease processes that have ample evidence available in order to better manage the patient, in the patient with end-stage kidney disease and new onset of atrial fibrillation, the situation becomes much more complicated. We believe randomized controlled trials for both the classical and the newer oral anticoagulants could provide evidence-based medicine protocols for the treatment of patients with ESRD and new-onset atrial fibrillation.
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Expert Opin Pharmacother · Jul 2014
ReviewMultidrug-resistant and extensively drug-resistant Gram-negative pathogens: current and emerging therapeutic approaches.
In the era of multidrug-resistant, extensively drug-resistant (XDR) and even pandrug-resistant Gram-negative microorganisms, the medical community is facing the threat of untreatable infections particularly those caused by carbapenemase-producing bacteria, that is, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii. Therefore, all the presently available antibiotics, as well as for the near future compounds, are presented and discussed. ⋯ Colistin is active in vitro and effective in vivo against XDR carbapenemase-producing microorganisms in the critically ill host, whereas tigecycline, with the exception of P. aeruginosa, has a similar spectrum of activity. The efficacy of combination therapy in bacteremias and ventilator-associated pneumonia caused by K. pneumoniae carbapenemase producers seems to be obligatory, whereas in cases of P. aeruginosa and A. baumannii its efficacy is questionable. Fosfomycin, which is active against P. aeruginosa and K. pneumoniae, although promising, shares poor experience in XDR infections. The in vivo validity of the newer potent compounds still necessitates the evaluation of Phase III clinical trials particularly in XDR infections.
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Restless legs syndrome (RLS) is a common condition characterized by paresthesia and an urge to move. Predominantly, symptoms occur at rest in the evening or at night, and they are alleviated by moving the affected extremity. RLS prevalence in the general population has been estimated to be approximately 5%. ⋯ Pharmacological treatment should be limited to those patients who suffer from clinically relevant RLS, that is, when symptoms impair the patient's quality of life, daytime functioning, social functioning or sleep. Treatment on demand is a clinical need in some RLS patients, and medications include carbidopa/levodopa, pramipexole, ropinirole, oxycodone, methadone, codeine and tramadol. Chronic RLS should be treated with either a nonergot dopamine agonist or an α-2-δ calcium channel ligand. A dopamine agonist is a more appropriate choice in the presence of depression and overweight. As α-2-δ ligands can alleviate chronic pain and may be helpful in treating anxiety and insomnia, the presence of any of these comorbidities may favor their use. For RLS present through much of the day and night, the use of long-acting agents, such as the rotigotine patch or gabapentin enacarbil should be considered. In refractory RLS, oral prolonged release oxycodone-naloxone should be considered.
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Expert Opin Pharmacother · Jun 2014
New protein kinase inhibitors in breast cancer: afatinib and neratinib.
Human epidermal growth factor receptor (HER) 2 is overexpressed in 20 - 25% of breast cancers, and has historically been a poor prognostic marker. The introduction of trastuzumab, the first fully humanized monoclonal antibody targeting HER2, has drastically changed the outcomes of metastatic breast cancers. However, despite initial response, most patients develop resistance. Recent data suggest that strategies targeting more than one member of HER family may circumvent trastuzumab resistance and confer synergistic effects. ⋯ HER2-targeted therapies have been widely used and greatly improved the outcome of HER2-positive breast cancer. Despite the accelerated advancement in recent years, several crucial questions remain unanswered, such as how to treat a prior resistance or affect a sanctuary site, that is, CNS metastasis. The novel next-generation TKIs, afatinib and neratinib, were rationally designed to overcome the resistance by targeting multiple HER family members and irreversibly binding the targets. In spite of the encouraging results of the afatinib and neratinib monotherapies, they have not been proven more efficacious in the combination therapies yet, even though multicenter international trials are still ongoing. The key tasks in the future are to study resistance pathways, design novel strategies to more efficiently test combinations for synergistic effects and identify biomarkers and novel imaging tools to guide individualized therapies.