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OBJECTIVES: To explore why some clinicians hesitate to use metformin in patients with liver disease and whether routine monitoring of transaminases before and during metformin therapy is substantiated. DATA SOURCES: A Medline literature search was conducted (1966 to June 2008) using the terms metformin, lactic acidosis, liver disease, chronic liver disease, hepatotoxicity, hypoxia, risks, and predisposing factors. DATA SYNTHESIS: Manufacturer prescribing information and some current medical and lay press literature caution against metformin use in patients with liver disease. This recommendation is interpreted variably by different prescribers, with some believing that the caution implies metformin can cause or worsen liver injury. Others believe that liver disease predisposes patients to developing lactic acidosis. A clearer understanding of how and when to screen for liver dysfunction in patients before and during metformin therapy is thus warranted. CONCLUSION: Metformin does not appear to cause or exacerbate liver injury and, indeed, is often beneficial in patients with nonalcoholic fatty liver disease. Nonalcoholic fatty liver frequently presents with transaminase elevations but should not be considered a contraindication to metformin use. Literature evidence of liver disease being associated with metformin-associated metabolic acidosis is largely represented by case reports. Most such patients had cirrhosis and were also actively using alcohol. Patients with cirrhosis, particularly those with encephalopathy, may have arterial hypoxemia, which heightens the risk of developing lactic acidosis. For this reason, identifying patients with cirrhosis before initiating metformin seems prudent. Because cirrhosis can exist in the face of normal liver transaminases, however, and because metformin is not considered intrinsically hepatotoxic, withholding metformin from patients with abnormal transaminases or routinely monitoring transaminases before or during metformin treatment is not supported.

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Concerns about cross-allergenicity between sulfonamide antibiotics and nonantibiotic sulfonamide-containing drugs continue to complicate pharmacotherapy. Several elegant investigations have demonstrated unequivocal lack of interaction between the sulfonamide group and either cellular or humoral immunity. The immunologic determinant of type I immunologic responses to sulfonamide antibiotics is the N1 heterocyclic ring, and nonantibiotic sulfonamides lack this structural feature. Many non-type I hypersensitivity responses to sulfonamide antibiotics are attributable to reactive metabolites that cause either direct cytotoxicity or humoral or cellular responses. Metabolite formation is stereospecific to the N4 amino nitrogen of the sulfonamide antibiotics, a structure not found on any nonantibiotic sulfonamide drugs. Cellular immune responses to sulfonamide antibiotics are responsible for many non-immunoglobulin E-mediated dermatologic reactions; however, the stereospecificity of T-cell response renders cross-reactivity between sulfonamide antibiotics and nonantibiotics highly unlikely. Apparent cross-reactivity responses to sulfonamide-containing drugs likely represent multiple concurrent, rather than linked, drug hypersensitivities.

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OBJECTIVE: To implement computer-assisted learning workshops into pharmacokinetics courses in a doctor of pharmacy (PharmD) program. DESIGN: Workshops were designed for students to utilize computer software programs on laptop computers to build pharmacokinetic models to predict drug concentrations resulting from various dosage regimens. In addition, students were able to visualize through graphing programs how altering different parameters changed drug concentration-time curves. Surveys were conducted to measure students' attitudes toward computer technology before and after implementation. Finally, traditional examinations were used to evaluate student learning. ASSESSMENT: Doctor of pharmacy students responded favorably to the use of wireless laptop computers in problem-based pharmacokinetic workshops. Eighty-eight percent (n = 61/69) and 82% (n = 55/67) of PharmD students completed surveys before and after computer implementation, respectively. Prior to implementation, 95% of students agreed that computers would enhance learning in pharmacokinetics. After implementation, 98% of students strongly agreed (p < 0.05) that computers enhanced learning. Examination results were significantly higher after computer implementation (89% with computers vs. 84% without computers; p = 0.01). CONCLUSION: Implementation of wireless laptop computers in a pharmacokinetic course enabled students to construct their own pharmacokinetic models that could respond to changing parameters. Students had greater comprehension and were better able to interpret results and provide appropriate recommendations. Computer-assisted pharmacokinetic techniques can be powerful tools when making decisions about drug therapy.

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Concerns about cross-allergenicity between sulfonamide antibiotics and nonantibiotic, sulfonamide-containing drugs persist and can complicate patients' drug therapy unnecessarily. No interaction between the human immune system and the sulfonamide functional group has been demonstrated. The immunologic determinant of type I, immediate hypersensitivity responses to sulfonamide antibiotics is the N1 heterocyclic ring. Nonantibiotic sulfonamides do not contain this structural feature. Non-type I hypersensitivity responses to sulfonamide antibiotics are largely attributable to reactive metabolites that may cause either direct cytotoxicity or immunologic response. Formation of these metabolites is a stereospecific process that occurs at the N4 amino nitrogen of the sulfonamide antibiotics, a structure also not found on any nonantibiotic sulfonamide drugs. The stereospecificity of these reactions implies that cross-reactivity with nonantibiotic sulfonamide-containing drugs is highly unlikely; this assertion is supported by recent literature. However, T-cell recognition of unmetabolized, nonhaptenated parent sulfonamide antibiotic appears to occur in a small subset of hypersensitive patients. Several of the severe cutaneous reactions associated with sulfonamide antibiotics are mediated by T cells. It is not known whether T-cell recognition of antibiotic is related to the sulfonamide functional group. Until the mechanism of this recognition is elucidated, cross-reactivity with nonantibiotic sulfonamides appears to remain at least theoretically possible.

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