Drugs
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Approximately 72 million people in the US experience hypertension. Worldwide, hypertension may affect as many as 1 billion people and be responsible for approximately 7.1 million deaths per year. It is estimated that approximately 1% of patients with hypertension will, at some point, develop a hypertensive crisis. ⋯ Newer agents, such as clevidipine and fenoldopam, may hold considerable advantages to other available agents in the management of hypertensive crises. Sodium nitroprusside is an extremely toxic drug and its use in the treatment of hypertensive emergencies should be avoided. Similarly, nifedipine, nitroglycerin and hydralazine should not to be considered first-line therapies in the management of hypertensive crises because these agents are associated with significant toxicities and/or adverse effects.
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Pulmonary arterial hypertension (PAH) is a devastating disease, which is associated with a 1-year survival of about 50% without specific treatment. Pulmonary vascular remodelling, thrombosis and vasoconstriction are thought to be directly involved in increasing pulmonary vascular resistance (PVR), which, left untreated, ultimately leads to right ventricular failure and death. A total of 10-12% of patients with systemic sclerosis (SSc) develop PAH, which is a leading cause of mortality in these patients. ⋯ There is growing evidence that combination therapies targeting different pathophysiological steps may be necessary to effectively treat SSc-PAH. The COMPASS-1 study has reported an acute haemodynamic benefit in PAH when a single-dose of sildenafil is used in combination with bosentan and COMPASS-2 will investigate whether this acute response translates into long-term benefit. Well designed morbidity and mortality trials in SSc-PAH should help increase our understanding and treatment of this orphan disease.
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Uncomplicated urinary tract infections (uUTIs) are common in adult women across the entire age spectrum, with mean annual incidences of approximately 15% and 10% in those aged 15-39 and 40-79 years, respectively. By definition, UTIs in males or pregnant females and those associated with risk factors known to increase the risk of infection or treatment failure (e.g. acquisition in a hospital setting, presence of an indwelling urinary catheter, urinary tract instrumentation/interventions, diabetes mellitus or immunosuppression) are not considered herein. The majority of uUTIs are caused by Escherichia coli (70-95%), with Proteus mirabilis, Klebsiella spp. and Staphylococcus saprophyticus accounting for 1-2%, 1-2% and 5-10% of infections, respectively. ⋯ If a beta-lactam is chosen, it should be given for 7 days. Management of uUTIs can frequently be triaged to non-physician healthcare personnel without adverse clinical consequences, resulting in substantial cost savings. It can be anticipated that the optimal approach to the management of uUTIs will change substantially in the future as a consequence of antimicrobial resistance.
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The fentanyl transdermal matrix patch is approved in Japan for the management of moderate to severe cancer-related pain in adults. Bioequivalence, in terms of exposure and the maximum and minimum serum concentrations, has been established between the fentanyl transdermal matrix patch 16.8 mg (100microg/h) and the fentanyl transdermal reservoir patch 10 mg (100microg/h) after single and multiple applications. The fentanyl transdermal matrix patch 2.1-8.4 mg (12.5-50microg/h) effectively managed chronic cancer-related pain in adults in a noncomparative, multicentre, phase II study; 89.4% of recipients rated their global assessment of pain as 'very satisfied', 'satisfied' or 'neither satisfied nor dissatisfied'. ⋯ Given the nature of the therapy, the tolerability profile of the fentanyl transdermal matrix patch was generally acceptable. Topical adverse events included erythema, application-site irritation and pruritus. In general, patients and physicians preferred the fentanyl transdermal matrix patch over the fentanyl transdermal reservoir patch in the pilot study.
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Review
Bivalirudin: in patients with acute coronary syndromes : planned for urgent or early intervention.
Bivalirudin is a 20-amino acid synthetic polypeptide that directly inhibits both fibrin-bound and soluble thrombin. In a randomized, open-label, phase III study (ACUITY) in 13,819 patients with acute coronary syndromes (unstable angina or non-ST-segment elevation myocardial infarction) in whom urgent or early intervention was planned, both bivalirudin plus a glycoprotein (GP) IIb/IIIa inhibitor and bivalirudin alone were noninferior to heparin plus a GP IIb/IIIa inhibitor for the primary endpoint of composite ischaemia (myocardial infarction, unplanned revascularization or death from any cause) at 30 days. The primary endpoint of major bleeding not related to coronary artery bypass graft surgery had occurred in significantly fewer recipients of bivalirudin alone than of heparin plus a GP IIb/IIIa inhibitor after 30 days. ⋯ Bivalirudin alone was also associated with a significantly lower incidence of the primary net clinical outcome endpoint (composite ischaemia or major bleeding) after 30 days. Bivalirudin plus a GP IIb/IIIa inhibitor was noninferior to the heparin regimen with regard to this endpoint. The findings of ACUITY at 1 year indicate that both bivalirudin plus a GP IIb/IIIa inhibitor and bivalirudin alone were as effective as heparin plus a GP IIb/IIIa inhibitor with regard to the long-term incidence of composite ischaemia and all-cause mortality.