Drugs
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The past decade has witnessed significant progress in the management of invasive aspergillosis. Potent, relatively non-toxic antifungal drugs, data on early chest CT scanning and the availability of a non-invasive diagnostic test (serum galactomannan) are the key advances; among these, the contribution of the recently available drugs is the most significant. Safer and earlier intervention resulting in reduced mortality and improved outcome is being demonstrated. ⋯ Reports of emergence of less-susceptible Aspergillus spp. during azole therapy are of concern and close monitoring is needed. Remarkably, the era of polyenes appears to be nearing the end in the therapy of invasive aspergillosis. The promise of newer classes of drugs, immune-modulating therapies and vaccines are exciting future additions to the arsenal against invasive aspergillosis.
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Sildenafil citrate (Revatio), an inhibitor of phosphodiesterase type 5 (PDE5), is approved for use in the US, Europe and other countries for the treatment of pulmonary arterial hypertension (PAH). Oral sildenafil 20 mg three times daily added to conventional background therapy was significantly more effective than placebo at increasing exercise capacity in patients with idiopathic PAH or PAH associated with connective tissue diseases or repaired congenital systemic-to-pulmonary shunts. ⋯ Sildenafil provides benefits in terms of exercise capacity when added to epoprostenol; however, these findings come from a trial that did not use the approved dosage of sildenafil. In conclusion, sildenafil is an effective oral treatment option for patients with PAH.
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Alvimopan, a trans-3,4-dimethyl-4-(3-hydroxy-phenyl) piperidine, is a selective, peripherally acting micro-opioid receptor antagonist that is available for short-term use in hospitalized patients who have undergone bowel resection. The efficacy of alvimopan in the management of postoperative ileus has been evaluated in five phase III trials; four conducted in North America and one conducted in Europe/Australasia. Patients who had undergone partial large or small bowel resection surgery with primary anastomosis were randomized to receive alvimopan 12 mg or placebo as a single oral pre-operative dose followed by twice-daily administration for up to 7 days postoperatively. ⋯ In the phase III trials conducted in North America, the time to writing the hospital discharge order was 13-21 hours sooner with alvimopan than with placebo. Alvimopan did not reduce opioid-induced analgesia and/or increase the amount of opioids administered postoperatively. Short-term alvimopan was generally well tolerated in adults undergoing bowel resection.
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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.