Current pharmaceutical design
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Granulumatosis with polyangiitis (wegener's)/GPA microscopic polyangiitis (MPA) and Churg Strauss syndrome (CSS) are primary systemic vasculitides which predominantly affect small vessels, showing a high association with a positive C/PR3-ANCA in GPA and P/MPO-ANCA in MPA, so called ANCA-associated vasculitides (AAV). The diagnostic work-up relies on an interdisciplinary approach including imaging techniques and laboratory tests in order to assess disease stage and extent. The golden standard remains the histological proof of a necrotizing, pauci-immune small vessel vasculitis, in GPA additionally non-caseating granuloma is found mainly in the respiratory tract. ⋯ When remission is achieved, usually after 3-6 months of induction treatment, cyclophosphamide is switched to azathioprine as maintenance of remission drug. Alternative therapies are methotrexate provided the kidney function is normal or Leflunomide in the long-term follow-up the relapse rate in ANCA-associated vasculitis is approximately 50% in 5 years, irrespective of the drug used for maintenance treatment. The relapse rate is significantly higher in GPA than in MPA and CSS.
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This review provides an overview of the immunological effects of commonly used analgesic opioid drugs, focusing mainly on two aspects: the mechanisms involved and the potential clinical relevance. The immunomodulatory effects of morphine have been characterized in animal and human studies. Morphine decreases the effectiveness of both natural and acquired immunity, interfering with intracellular pathways involved in immune regulation, both directly and indirectly via the activation of central receptors. ⋯ It is also emerging that not all opioids induce the same immunosuppressive effects and evaluating each opioid profile is important for appropriate analgesic selection. The impact of the opioid-mediated immune effects could be particularly dangerous in selective vulnerable populations, such as the elderly or immunocompromised patients. Indeed, it is evident that the possibility of reaching adequate and equivalent pain control by choosing either immunosuppressive drugs or drugs without an effect on immune responses may be an important consideration in opioid therapy.
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Nausea and vomiting are common gastrointestinal symptoms following opioid administration, for either chronic or acute pain management. As a consequence, patients' dissatisfaction has a negative impact on treatment efficacy. ⋯ Preventive strategies and therapeutic approaches are evaluated in the perioperative setting and in chronic pain. Newer drugs include second generation serotonin receptor antagonists (palonosetron) and neurokinin-1 (NK-1) antagonists (aprepitant).