Hepatotoxicity associated with carvedilol.

OBJECTIVE: To report a severe episode of pruritus and elevated serum transaminases in a patient who was receiving carvedilol. CASE SUMMARY: A 40-year-old white man who had been taking carvedilol for the treatment of cardiomyopathy presented to the emergency department with pruritus over his entire body. Laboratory tests showed elevated serum transaminases. Carvedilol was discontinued and the patient received hydroxyzine hydrochloride to relieve symptoms. Liver function test results returned to normal in three weeks. Approximately one year later the patient was started on metoprolol and within 10 days again developed pruritus. The patient was told to discontinue the metoprolol immediately. At the time the metoprolol was stopped the liver function test results were normal. DISCUSSION: To the best of our knowledge, the adverse reaction presented in this case report is rare. The etiology of this adverse reaction remains unknown but suggests a possible adverse reaction that may recur if the patient is switched to another beta-adrenergic blocker. The liver function test abnormalities appear to return to normal on discontinuation of carvedilol. CONCLUSIONS: Carvedilol may cause pruritus and elevated liver function test results. This reaction may recur if the patient is changed to an alternative beta-adrenergic blocker. Patients taking carvedilol should be monitored for signs and symptoms of hepatotoxicity. If elevated liver function test results are noted, carvedilol should be discontinued.

Acute profound thrombocytopenia following abciximab therapy.

OBJECTIVE: To report a case of acute, profound thrombocytopenia (APT), defined as an abrupt drop in platelet count to <20,000/mm3 that occurred within 24 hours of administration of an abciximab bolus, to summarize other abciximab-associated APT cases reported in the literature, to review the postulated mechanisms behind this reaction, and to emphasize the importance of periodically monitoring platelet counts after initiating abciximab therapy. DATA SOURCES: MEDLINE and Index Medicus searches restricted to English-language literature from 1993 through June 1999 were conducted. MeSH headings included abciximab, ReoPro, thrombocytopenia, and glycoprotein IIb-IIIa (GP IIb-IIIa) inhibitors. References of the articles obtained were also reviewed. DATA EXTRACTION: Search and evaluation were focused on published case reports and reviews of abciximab-induced APT, as well as the incidence of thrombocytopenia from the drug compared with that from other GP IIb-IIIa inhibitors. DATA SYNTHESIS: Platelet aggregation has been identified as the structural basis for coronary thrombosis. This may lead to ischemic complications during acute coronary syndromes or following coronary intervention procedures. The use of GP IIb-IIIa inhibitors such as abciximab as antiplatelet agents has been effective in reducing these ischemic complications. We summarize 15 published cases of abciximab-associated APT gathered from data on 2,482 patients treated with the drug. Prior to suspecting abciximab, other potential causes of thrombocytopenia should be evaluated. It is important to monitor the platelet count at baseline, two hours after initiating abciximab, and 24 hours after initiation of therapy or prior to discharge, whichever comes first, to identify patients at risk for developing APT. If APT occurs and is left untreated, it can produce excessive hemorrhage and ischemia, potentially leading to death. Platelet transfusions have been more effective than immunoglobulin in the management of APT. CONCLUSIONS: Abciximab-induced APT has a low incidence of occurrence. If it does develop and is not recognized or treated promptly, it can lead to serious hemorrhagic complications. Consequently, monitoring the platelet count two hours after initiation of the infusion is essential. If APT develops, abciximab should be discontinued and a platelet transfusion should be considered.

Combination therapy with interferon and ribavirin in the treatment of chronic hepatitis C infection.

OBJECTIVE: To review and critique the medical literature regarding the combination of interferon and ribavirin in the initial treatment of chronic hepatitis C virus (HCV) infection. DATA SOURCES: A MEDLINE search (January 1966-June 1999) was conducted to identify human clinical trials regarding the combination of interferon and ribavirin therapy for the initial treatment of chronic HCV. Bibliographies were reviewed for relevant literature. STUDY SELECTION: Clinical trials of combination interferon and ribavirin for the treatment of chronic HCV in interferon-naïve adults were reviewed. DATA SYNTHESIS: The combination of ribavirin and interferon in the treatment of chronic HCV has been beneficial in patients who are interferon-naïve. Patients with predictors of poor response, such as baseline cirrhosis, male gender, age >40 years, high baseline viral loads (>2 x 10(6) copies/mL), and genotype 1 respond better to combination treatment when compared with those who receive interferon monotherapy. Patients with genotype 1 and/or high viral loads may benefit most from 48 weeks of combination therapy; however, adverse effects are of greater concern in these patients. Monitoring can limit these complications. CONCLUSIONS: Combination therapy is effective in the treatment of interferon-naive patients with chronic HCV infection. Patients should be evaluated for duration of treatment with combination therapy by determination of predictors of response. Further trials are needed to more closely evaluate the duration of treatment and to determine the best patient population to receive combination therapy.

Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus: chronic infections and coronary heart disease.

We conducted a MEDLINE search of the English-language literature from 1966-1999 on the association of chronic infections with Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus (CMV) with coronary heart disease (CHD); additional literature was retrieved from references of selected articles. All human studies were included. Abstracts were excluded because of limited data. Chronic infections in CHD are speculated to be due to serum antibody concentrations of one or more of the three organisms. Data for H. pylori and CMV are difficult to interpret due to the confounding factor of childhood poverty and studies conducted in transplant recipients, respectively. Chlamydia pneumoniae data appear stronger with elevated IgG antibody titers (> or = 64) as a risk factor. Larger prospective studies are warranted to determine an association with CHD before universal prophylaxis or treatment of these chronic infections.

Role of lamivudine in the treatment of chronic hepatitis B virus infection.

OBJECTIVE: To examine the evidence regarding the therapeutic effectiveness of lamivudine in the treatment of chronic hepatitis B virus (HBV) infection in immunocompetent patients. DATA SOURCES: Using chronic hepatitis B and lamivudine as MeSH headings, MEDLINE was searched from 1966 to September 1998 for all published randomized controlled trials evaluating lamivudine in chronic HBV infection. Relevant articles from selected bibliographies were also retrieved. STUDY SELECTION: Only randomized, single- and double-blind trials in human HBV carriers published in the English language were included. DATA SYNTHESIS: Evidence from the controlled trials suggests that lamivudine has a therapeutic effect in suppressing HBV replication in immunocompetent patients. Lamivudine 100 mg/d appears to suppress HBV replication in as many as 97% of patients within two weeks after the initiation of therapy and is capable of suppressing histologic damages. However, viral suppression is effective only during the therapy; on discontinuation of lamivudine therapy, most patients return to the pretreatment condition. Viral resistance to lamivudine has been observed. Most patients with chronic HBV infection appear to tolerate 100 mg/d of lamivudine therapy. CONCLUSIONS: Evidence has shown that oral lamivudine 100 mg/d will produce rapid and significant suppression of viral replication in immunocompetent patients with chronic HBV infections. Treatment periods up to one year have been effective and well tolerated. The suppression of viral replication may not be sustained after cessation of lamivudine therapy, and very few patients have complete elimination of HBV during therapy. Therefore, long treatment periods may be necessary. Efficacy and tolerability of treatment beyond one year need to be investigated. Resistance to lamivudine has been reported in patients receiving therapy. A combination anti-HBV regimen using lamivudine and other agents with different mechanisms of action should be investigated to maximize the elimination of the viral infection while minimizing or preventing damage to the liver cells and tissues and the development of viral resistance.

Allergic-type reactions to corticosteroids.

OBJECTIVE: To review reported cases of suspected allergic reactions to various corticosteroids. DATA SOURCES: A MEDLINE search (January 1966-December 1997) was performed to obtain case reports and review articles on allergic-type reactions to corticosteroids. Further references were obtained from these publications. STUDY SELECTION: Reports involving allergic or allergic-type reactions to systemic administration of corticosteroids were chosen for this review. An allergic-type reaction was defined as any reaction after administration of the drug that involved the appearance of adverse symptoms that are characteristic of unwanted immune responses. These symptoms include rash, sneezing, dyspnea, edema, bronchospasm, or death. Articles were excluded from the evaluation if they described reactions to topical, intraarticular, or ophthalmic corticosteroid administration. DATA SYNTHESIS: Corticosteroids are medications that are often used to treat allergic reactions. However, it appears that patients can also have allergic-type reactions to these agents. The severity of the reaction can vary from a rash to anaphylaxis or death. Both immediate and delayed reactions can occur. Allergic-type reactions are reported to occur more frequently in asthmatic and renal transplant patients than other patient populations. However, it is questionable whether all of these are true allergic responses, as there is conflicting evidence regarding the mechanism of the reaction. The most commonly implicated corticosteroids are methylprednisolone and hydrocortisone, but reactions have also occurred with others. Intradermal skin testing can help determine cross-sensitivity, although its value has not been conclusively demonstrated. CONCLUSIONS: Clinicians should be aware that allergic reactions to corticosteroids are possible. Worsening of symptoms may not always mean treatment failure, but may indicate an allergic reaction. High doses of corticosteroids (> or = 500 mg) should be given over 30-60 minutes, and patients should be observed after administration for at least the same time period. Asthmatics, renal transplant patients, and hemodynamically unstable patients may be at higher risk for adverse events. If a patient is found to be allergic to one corticosteroid, intradermal skin testing may help identify another corticosteroid that can be tolerated.

The role of zinc lozenges in treatment of the common cold.

OBJECTIVE: To summarize and critique the medical literature on the use of zinc lozenges for treatment of the common cold. DATA SOURCES: MEDLINE searches (January 1966-June 1997) identified human clinical trials on the use of zinc lozenges for the treatment of the common cold. Bibliographies were also reviewed for relevant articles. STUDY SELECTION: Double-blind, placebo-controlled trials of zinc lozenges in adults for the treatment of the common cold, with the clinical end points of reduction in duration and/or severity of cold symptoms. DATA EXTRACTION: All double-blind placebo-controlled, human clinical trials on the use of zinc lozenges for the treatment of the common cold were included. DATA SYNTHESIS: The use of zinc lozenges in the treatment of the common cold has been suggested to reduce the duration and severity of cold symptoms. Of eight double-blind, placebo-controlled trials, four found zinc lozenges to be effective, while the other four reported no difference between zinc and placebo therapy. Potential reasons for the discrepancy between the results of these trials include inadequate placebo control, formulation of the lozenge, and the dose of zinc used. Common adverse effects include unpleasant taste, mouth irritation, and nausea. CONCLUSIONS: Treatment of the common cold with zinc gluconate lozenges, using adequate doses of elemental zinc, may be effective in reducing duration and severity of cold symptoms. The benefit appears to be maximal if the lozenges are started immediately after the onset of symptoms. The formulation of the lozenges also appears to be important because the addition of citric acid or tartaric acid may reduce efficacy due to chelation of zinc ion. Although zinc gluconate lozenges have dominated clinical trials thus far, further studies are needed to demonstrate the efficacy of zinc acetate lozenges and to determine whether their adverse effect profile is more favorable to that of zinc gluconate lozenges. Patients should play an important role in the decision-making process and must decide whether the benefit gained from treatment with zinc lozenges outweighs the potential adverse effects.

Metformin and insulin: is there a role for combination therapy?

OBJECTIVE: To review the literature on concomitant insulin and metformin therapy in patients with type 1 diabetes to determine the potential for combination therapy. DATA SOURCES: A MEDLINE and bibliographic search (1966-1996) of the literature pertaining to metformin and phenformin and their combined use with insulin in the treatment of patients with type 1 diabetes mellitus was performed. STUDY SELECTION: All human studies using metformin with insulin were included in the analysis. Studies using phenformin with insulin were also included due to its similarities to metformin. DATA SYNTHESIS: The recent availability of metformin provides some new options for treating diabetes mellitus. One possibility is the use of this medication in conjunction with insulin in patients with type 1 diabetes. Although this seems like a potentially beneficial combination, there is currently no recommendation for use in this manner. Experience with combination metformin and insulin therapy has consistently demonstrated a reduction in insulin requirements. Studies have not been of necessary size or duration to definitively prove the benefits of this insulin dose reduction or any other benefits of combination therapy. CONCLUSIONS: When metformin is added to insulin therapy, insulin requirements are likely to decrease. Although one would anticipate benefits from reduction in circulating insulin concentrations, the studies do not provide data to determine if benefits of combination therapy outweigh risks. Further studies of larger size and longer duration are needed before the use of metformin with insulin can be routinely recommended in patients with type 1 diabetes.

Meperidine-related seizures associated with patient-controlled analgesia pumps.

OBJECTIVE: To report three cases of meperidine-related seizures when meperidine was administered via patient-controlled analgesia pump (PCAP) and to review literature related to meperidine-associated seizures. DATA SOURCES: Case reports and review articles identified by a computerized search (MEDLINE) and manual search (Index Medicus). DATA SYNTHESIS: PCAPs are being used frequently to relieve the pain of sickle cell crisis as well as pain from many other etiologies. We report three cases of meperidine-related seizures associated with its administration via PCAP. Each of the patients received either relatively high doses, long-term therapy, or both. Meperidine has been associated with seizure activity when administered via traditional routes. Previously identified risk factors for the development of meperidine-related seizures include renal failure, high meperidine dosages, and coadministration of hepatic enzyme-inducing medications or phenothiazines. CONCLUSIONS: Meperidine administered via PCAP may be associated with seizures. Optimally, an alternative analgesic should be administered when this route is used.