Drugs
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Enoxaparin (PK 10169) belongs to the group of low molecular weight heparins which have a greater bioavailability and longer half-life than unfractionated heparin, permitting less frequent subcutaneous administration. In well controlled trials in surgical venous thrombosis (DVT), enoxaparin has demonstrated prophylactic efficacy against venographically confirmed DVT at least equal to that observed with unfractionated heparin. Efficacy has also been demonstrated in patients at moderate risk and in limited investigations using 125I-fibrinogen scanning in nonsurgical patients at risk of DVT; in addition, enoxaparin appears to provide effective treatment of established DVT. In clinical studies, enoxaparin has also prevented coagulation of extracorporeal circulation, maintaining the patency of the circuit in patients undergoing haemodialysis. Thus, enoxaparin represents an effective alternative in the prophylaxis and treatment of thrombosis, with the convenience of less frequent administration than unfractionated heparin and the possible advantage of a lesser propensity for bleeding complications. ⋯ In prevention of postoperative DVT in patients undergoing orthopaedic surgery, subcutaneous enoxaparin doses of 40mg once daily (from 12 hours preoperatively) are employed in Europe, while a dosage of 30mg twice daily (from 12 to 24 hours postoperatively) has been used in North America; in general surgery and in 'moderate risk' patients dosages of 20mg once daily have also been employed. Enoxaparin 2 mg/kg/day is effective in the treatment of established DVT, while 1 mg/kg appears to be effective in preventing coagulation of the extracorporeal circuit in patients undergoing haemodialysis. For daily dosages higher than 60mg, the elimination of enoxaparin may be prolonged in patients with severe renal dysfunction; however, an appropriate nomogram for dosage reduction has not yet been devised.
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Review
Newer neuromuscular blocking drugs. An overview of their clinical pharmacology and therapeutic use.
Four new nondepolarising muscle relaxants, pipecuronium bromide, doxacurium chloride, mivacurium chloride and Org 9426 (rocuronium) offer alternatives to the established agents atracurium besilate and vecuronium bromide. Pipecuronium and Org 9426 are steroidal compounds, the latter being a monoquaternary agent, whereas doxacurium and mivacurium are bisquaternary benzylisoquinolinium compounds. Pipecuronium and doxacurium have a relatively slow onset and a long duration of action. ⋯ The rapid onset of effect could be useful for early intubation as an alternative to suxamethonium chloride. However, much more clinical experience is needed with this agent, particularly with regard to duration of action of larger doses and occurrence of side effects. The drug is mainly eliminated via the liver.
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Sumatriptan is a serotonin1 (5-HT1) receptor agonist, which is effective in the acute treatment of migraine headache. Its antimigraine activity is believed to derive from selective vasoconstriction of cranial blood vessels which are dilated and distended during migraine headache and/or from inhibition of neurogenically mediated inflammation in the dura mater. In placebo-controlled comparative studies, sumatriptan reduced migraine headache from 'moderate or severe' to 'mild or none' within 2 hours in 50 to 73% of patients following oral administration of 100 or 200 mg, and within 1 hour in 70 to 80% of patients following subcutaneous doses of 6 to 8 mg or intranasal doses 20 mg into each nostril. ⋯ It provides rapid relief from debilitating symptoms in a high percentage of patients, particularly after subcutaneous administration. At this stage in its development a number of questions remain to be answered - most notably whether repeat doses will help prevent recurrent attacks and which patients are most likely to respond to therapy. Nevertheless, sumatriptan presently offers a combination of efficacy and tolerability that is unique in this particular clinical setting.
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The main aim of sedation in the critically ill patient is to provide relief from anxiety and pain. The current, ideal level of sedation should leave a patient who is lightly asleep but easily roused. No single regimen is suitable for all patients. ⋯ Attention to the environment is also important. Midazolam and morphine given by intermittent bolus or by infusion are the mainstay of most regimens. Propofol is ideal for short periods of care on the ICU, and during weaning when longer acting agents are being eliminated.
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Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) is a polypeptide hormone produced through recombinant DNA technologies in glycosylated (yeast or mammalian expression systems) or nonglycosylated (Escherichia coli expression system) form. It is a multilineage haematopoietin which stimulates proliferation and differentiation of bone marrow myeloid progenitors and increases peripheral white blood cell counts when administered systemically. Treatment is generally well tolerated, although mild to moderate flu-like symptoms are common and rGM-CSF-induced fever and fluid retention may be problematic in occasional patients. rGM-CSF accelerates recovery of peripheral neutrophil counts after bone marrow transplantation, and results of a placebo-controlled randomised trial correlate this with reduced infectious episodes and shortened length of hospitalisation in patients with lymphoid malignancies. ⋯ Recombinant colony-stimulating factors are a new therapeutic modality; hence many aspects of their use remain to be clarified. Nonetheless, as one of a small group of novel agents rGM-CSF has major potential in the management of myelosuppression secondary to cytoreductive therapy with or without bone marrow transplantation, and in amelioration of disturbed myelopoiesis. It represents an important application of biotechnology to a difficult area of therapeutics.