Drugs
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Ganciclovir is a nucleoside analogue which is used to treat and prevent cytomegalovirus (CMV) infection. Most recent clinical studies of ganciclovir in transplant recipients have focused on preventive approaches. When ganciclovir was last reviewed in Drugs in 1994, substantial data on post-transplantation CMV prophylaxis with this drug were available only for patients undergoing allogeneic bone marrow transplantation (BMT). Two strategies had emerged: prophylaxis for all patients or early treatment started after detection of asymptomatic CMV infection. Subsequently, a large double-blind study has shown that ganciclovir prophylaxis is more effective than early treatment in preventing early CMV disease after allogeneic BMT and is not associated with an increased incidence of neutropenia. However, mortality for the 2 strategies was similar. The efficacy of prophylactic intravenous ganciclovir in liver transplant recipients [including high risk donor seropositive/recipient seronegative (D+/R-) or antilymphocyte-treated patients] is now well established. Prophylaxis with oral ganciclovir was effective both overall and in D+/R-patients in a large placebo controlled study, and prolonged intravenous ganciclovir was significantly more effective than high dose aciclovir (acyclovir) in seropositive liver recipients. Early treatment with ganciclovir has proved useful in this setting. More limited data indicate that CMV prophylaxis with intravenous ganciclovir may be useful after heart or lung transplantation but its value in D+/-patients remains unclear. Combined chemoimmunotherapy may be valuable in these high risk patients but controlled data are lacking. Targeted prophylaxis with intravenous ganciclovir is effective in renal transplant recipients receiving antilymphocyte therapy; the role of oral ganciclovir in this setting is less clear. The value of ganciclovir in D+/- renal transplant recipients and its efficacy compared with high dose aciclovir have not been determined. ⋯ Ganciclovir is the only antiviral chemotherapy which reduces the risk of CMV infection or disease after most types of major transplantation. Unresolved issues include the best (and most cost-effective) use of ganciclovir and aciclovir after allogeneic BMT, the efficacy of oral ganciclovir compared with other anti-CMV regiments, the potential clinical effect of viral resistance during prolonged ganciclovir exposure and the value of ganciclovir in certain high risk transplant populations. In the meantime, ganciclovir has an important role in the prevention of CMV infection and disease after bone marrow and liver transplantation and is likely to gain wider clinical use in heart, lung and kidney transplant recipients.
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Sumatriptan is a selective agonist at serotonin 5-HT1-like receptors, including 5-HT1B/1D subtypes. It is an effective treatment for acute migraine attacks and the injectable form has also shown efficacy in the treatment of cluster headaches. In placebo-controlled clinical trials, sumatriptan, administered subcutaneously, orally, intranasally or rectally was significantly more effective than placebo in relieving migraine headache and in producing resolution or reduction of other symptoms associated with migraine, including nausea, photophobia and phonophobia. Improvements in clinical disability were also significantly greater after sumatriptan than after placebo. Headache recurred in 21 to 57% of patients who received oral or subcutaneous sumatriptan, but most patients responded to a second dose of the drug. Results of comparative trials showed that subcutaneous sumatriptan 6 mg was significantly more effective than either patients' usual antimigraine treatments or intranasal dihydroergotamine mesylate 1 mg in relieving migraine headache. Subcutaneous sumatriptan 6 mg and subcutaneous dihydroergotamine mesylate 1 mg provided similarly effective migraine relief, but the headache recurrence rate was significantly higher after sumatriptan than after this formulation of dihydroergotamine mesylate. Response rates achieved after oral sumatriptan were similar to those reported after treatment with oral naratriptan, rizatriptan or lysine acetylsalicylate plus metoclopramide. Treatment of acute migraine attacks with oral or subcutaneous sumatriptan leads to less loss of workplace productivity than other antimigraine therapies. Several pharmacoeconomic analyses showed that gains in workplace productivity in sumatriptan recipients ranged from 12.1 to 89.8 hours per patient per year. Significant improvements from baseline in overall health-related quality-of-life scores were also experienced by sumatriptan recipients. Sumatriptan is generally well tolerated. Nausea, vomiting, malaise and fatigue are the most common adverse events with oral sumatriptan. Injection site reactions occur in 10 to 40% of patients receiving the drug subcutaneously. A bitter taste at the back of the mouth occurs frequently after intranasal administration. Serious adverse events occur in about 0.14% of patients with migraine treated with sumatriptan. As the drug is associated with the rare development of cardiovascular effects, it is contraindicated in patients with a history of cardiovascular disease. ⋯ Despite its relatively high acquisition cost, reductions in lost workplace productivity experienced by patients treated with sumatriptan may result in savings in the overall cost of migraine to society. Thus, sumatriptan is a useful first- or second-line treatment option for patients with moderate or severe migraine.
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Colloid solutions have been developed and used over the past 70 years as expanders of the intravascular space, based on an understanding of Starling's law. Increasing osmotic pressure with colloidal products has remained an attractive theoretical premise for volume resuscitation. Indeed, colloids have been shown to increase osmotic pressure in clinical practice; however, the effects are short-lived. ⋯ Although severe coagulopathies have been reported in sporadic cases, hetastarch has not been shown to increase postoperative bleeding compared with albumin therapy, even in large doses (3 L/day). Despite some theoretical advantages compared with crystalloid therapy, colloid administration has not been shown to decrease the risk of acute lung injury or to improve survival. Specific indications for colloid products include hypoproteinaemic or malnourished states, patients who require plasma volume expansion who are unable to tolerate larger amounts of fluid, orthopaedic and reconstructive procedures requiring prevention of thrombus formation and leukapheresis.
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Review Comparative Study
Liposomal amphotericin B. Therapeutic use in the management of fungal infections and visceral leishmaniasis.
Incorporation of amphotericin B into small unilamellar liposomes (AmBisome) alters the pharmacokinetic properties of the drug, but allows it to retain significant in vitro and in vivo activity against fungal species, including Candida, Aspergillus and Cryptococcus, and parasites of the genus Leishmania. Used as prophylaxis against fungal infections in immunocompromised patients, liposomal amphotericin B appeared to reduce the incidence of both fungal colonisation and proven fungal infections, but did not affect overall survival. Empirical therapy with liposomal amphotericin B in immunocompromised adults or children with suspected fungal infections was at least as effective as therapy with conventional amphotericin B. ⋯ Use of the drug is facilitated by its greatly improved tolerability profile compared with conventional amphotericin B. Because of this, liposomal amphotericin should be preferred to conventional amphotericin B in the management of suspected or proven fungal infections in immunocompromised patients with pre-existing renal dysfunction, amphotericin B-induced toxicity or failure to respond to conventional amphotericin B. Liposomal amphotericin B may also be considered for first- or second-line treatment of immunocompetent patients with visceral leishmaniasis.
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Therapy for Gram-negative sepsis remains unsatisfactory despite a concerted effort to develop new treatments for this common, life-threatening syndrome. Current research continues on several fronts to improve the treatment options available to clinicians in the management of these critically ill patients. Recently, a greater understanding of the complex molecular basis of endotoxin-mediated pathophysiological effects in humans has generated a number of novel therapeutic agents for sepsis. ⋯ While considerable progress has been made, effective and new treatments for Gram-negative bacterial sepsis continues to elude us at the present time. This has been to the detriment of patients, investigators and pharmaceutical companies alike. It will require focused efforts by basic scientists, continued support by industry and enlightened study designs by clinical investigators to successfully develop antiendotoxin in therapies for use in septic patients in the future.