Drugs
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This article reviews the pharmacology, therapeutic efficacy and tolerability profile of intramuscularly injected onabotulinumtoxinA (onaBoNTA; BOTOX®) for headache prophylaxis in adults with chronic migraine, with a focus on UK labelling for the drug. The pharmacological actions of onaBoNTA include a direct antinociceptive (analgesic) effect; while not fully understood, the mechanism of action underlying its headache prophylaxis effect in chronic migraine is presumed to involve inhibition of peripheral and central sensitization in trigeminovascular neurones. Pooled findings from two large phase III studies of virtually identical design (PREEMPT [Phase III REsearch Evaluating Migraine Prophylaxis Therapy] 1 and 2) showed that treatment with up to five cycles of onaBoNTA (155-195 units/cycle) at 12-week intervals was effective in reducing headache symptoms, decreasing headache-related disability, and improving health-related quality of life (HR-QOL) in patients with chronic migraine, approximately two-thirds of whom were overusing acute headache medications at baseline. ⋯ Debate surrounding the PREEMPT studies has centred on the small treatment effect of onaBoNTA relative to placebo, the possibility that blinding was inadequate and the relevance of the evaluated population. Nonetheless, the totality of the data showed that onaBoNTA therapy produced clinically meaningful improvements in headache symptoms, functioning and HR-QOL; on the basis of these trials, it has become the first (and so far only) headache prophylactic therapy to be specifically approved for chronic migraine in the UK and US. Overall, onaBoNTA offers a beneficial, acceptably tolerated and potentially convenient option for the management of this highly disabling condition, for example in patients who are refractory to oral medications used for prophylaxis.
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Intra-abdominal infection (IAI) is a complex disease entity in which different aspects must be balanced in order to select the proper antimicrobial regimen and determine duration of therapy. A current classification indicates different faces of peritonitis. Primary peritonitis implies an intact gastrointestinal tract without overt barrier disruption. ⋯ The basis of antimicrobial therapy for IAI is that both Gram-negative and anaerobic bacteria should always be covered. In recent years, some newer agents such as doripenem, moxifloxacin and tigecycline have been added to the antimicrobial armamentarium for IAI. For patients in whom the source can be adequately controlled, antimicrobial therapy should be restricted to a short course (e.g. 3-7 days in peritonitis).