Sameh Trabelsi

Methotrexate Side Effects: Review Article

Methotrextae (MTX) is an antifolate first developed to treat certain types of cancer. It was used at higher doses as a cancer therapy and since 1990 it is used at much lower doses to treat rheumatic diseases [1]. Side effects of MTX high dose (MTX-HD) may be life threatening, however those of various doses of oral MTX are variable because of the interindividual variability of gastrointestinal absorption of this drug. Bone marrow, gastrointestinal mucosa and hair are particularly vulnerable to the effects of MTX, secondary to their high rate of cellular turnover [2] and because MTX concentration is inversly proportianal to renal clearance [2], renal toxicity is frequent with MTX-HD.

Estimation of Abbreviated Cyclosporine A Area under the Concentration-Time Curve in Allogenic Stem Cell Transplantation after Oral Administration.

Measurements of Cyclosporine (CsA) systemic exposure permit its dose adjustment in allogenic stem cell transplantation recipients to prevent graft-versus-host disease. CsA LSSs were developed and validated from 60 ASCT patients via multiple linear regressions. All whole-blood samples were analyzed by fluorescence polarization immunoassay (FPIA-Axym). The 10 models that have used CsA concentrations at a single time point did not have a good fit with AUC0–12 (R2 < 0.90). C 2 and C 4 were the time points that correlated best with AUC0–12 h, R2 were respectively 0.848, and 0.897. The LSS equation with the best predictive performance (bias, precision and number of samples) utilized three sampling concentrations was AUC0–12 h = 0.607 + 1.569 × C 0.5 + 2.098 × C 2 + 3.603 × C 4 (R2 = 0.943). Optimal LSSs equations which limited to those utilizing three timed concentrations taken within 4 hours post-dose developed from ASCT recipients patients yielded a low bias <5% ranged from 1.27% to 2.68% and good precision <15% ranged from 9.60% and 11.02%. We propose an LSS model with equation AUC0–12 h = 0.82 + 2.766 × C 2 + 3.409 × C 4 for a practical reason. Bias and precision for this model are respectively 2.68% and 11.02%.

Érythème pigmenté fixe à la sulfaguanidine

Resume Introduction L’erytheme pigmente fixe est une eruption consideree comme exclusivement medicamenteuse. Les classes de medicaments les plus incriminees sont les sulfamides, les tetracyclines et les pyrazoles. Nous rapportons 9 cas d’erytheme pigmente fixe a la sulfaguanidine qui est un sulfamide peu resorbe par voie orale. Observations Tous les malades ont eu un ou plusieurs episodes de reactivation d’erytheme pigmente fixe consecutifs a une automedication a la sulfaguanidine pour une diarrhee. Le nombre des lesions lors des recidives a augmente chez 7 malades sur 9. Le delai de reactivation des lesions a ete raccourci au fur et a mesure des poussees. Les mains ont ete les plus touchees par ces lesions (8 cas sur 9). Discussion La sulfaguanidine doit etre ajoutee a la liste des medicaments peu resorbes par voie digestive et qui peuvent induire un erytheme pigmente fixe.

Les colites médicamenteuses : revue de la littérature

Frequency of colitis induced by drugs is often under estimated. Antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDS) are usually incriminated. In this study, we classified colitis according to the main responsible drug with a focus on clinical symptomatology, physiopathology, evolution, and complications. We describe colitis due to antibiotics, NSAIDS, laxatives, vasoconstrictive agents, oestroprogestatives, chemotherapy and drugs induced microscopic colitis. The last one represents a particular case; it can be idiopathic, infectious or drugs induced. Its physiopathology is not well known and its diagnosis is based only on histologic criterion. Drug responsibility is easy to determine only for pseudomembranous colitis. In the other cases, chronology is very variable and the clinical, endoscopic and histological elements are rarely specific. Because of the large number of drugs that may induce colitis, it is necessary to search for potentially responsible drugs, especially if there is no obvious cause of the colitis.

Delayed Elimination of Methotrexate in a Patient Receiving Ciprofloxacin

High-dose methotrexate (HD-MTX) is indicated in neoplasic diseases. It is administrated at doses above 500 mg/m2 in association with alkaline hyperhydratation and folinic acid in order to interrupt the antifolinic activity of this chemotherapy.[1,2] It has several toxic side effects as mucosal ulcer, hepatitis and renal impairment.[2] This toxicity may be exacerbated by a delayed elimination of HD-MTX. Many factors may lead to the delayed elimination of HD-MTX such as renal impairment, third space fluid collections and drug-drug interactions. Non steroidal anti-inflammatory drugs (NSAIDs), probenicid, penicillin and sulfamethoxazole-trimethoprim are the most responsible of drug interactions with MTX.[3] We report herein a rare case of delayed elimination of HD-MTX associated with administration of ciprofloxacin.

Interaction médicamenteuse entre le tacrolimus et la théophylline chez un greffé rénal : à propos d’un cas

Le tacrolimus est un immunosuppresseur largement indiqué dans la greffe d’organes solides. [1] C’est un médicament métabolisé au niveau du foie par le CYP 450 3A4. De nombreuses interactions médicamenteuses sont observées avec les inducteurs et les inhibiteurs enzymatiques du système cytochrome P450, [2] entraînant dans le premier cas un risque de rejet de greffe par diminution des concentrations sanguines du tacrolimus et dans le second un risque de toxicité par augmentation de ses concentrations sanguines. Les principaux inducteurs enzymatiques interagissant avec le tacrolimus sont les anticonvulsivants, la rifampicine et les extraits de millepertuis. [2,3] Concernant les inhibiteurs enzymatiques, il s’agit essentiellement de macrolides, antiprotéases, antifongiques azolés, antagonistes calciques, amiodarone et inhibiteurs de la pompe à protons. [2,3] Nous rapportons dans ce travail un cas d’interaction médicamenteuse très rarement observé, entre le tacrolimus et la théophylline.

Vancomycin Therapeutic Drug Monitoring in Cerebrospinal Fluid

Vancomycin penetrates poorly through the blood-brain barrier. Determination of vancomycin concentration in plasma is recommended. In contrast, its determination in cerebrospinal fluid (CSF) is rarely performed. We report the case of a 74-year-old man with post traumatic meningitis with vancomycin concentration measured in CSF.

Hypericum Humifusum Leaves Attenuates Hepatic Ischemia-Reperfusion Injury in a Rat Model

INTRODUCTION Effective prevention strategies require specific actions during the different phases of ischemia-reperfusion (I-R) injury. The objective of our study is to evaluate the effect of aqueous extract of Hypericum humifusum leaves (HHL) on liver I-R model in Rat. MATERIAL AND METHODS Animals were subjected to 90 min of hepatic ischemia followed by reperfusion (120 min). HHL extract (25 mg/mL/kg) was injected 15 min before reperfusion. To evaluate the effect of HHL extract on I-R, we have monitored transaminases levels, Malondialdehyde (MDA) concentration, histological lesions (apoptosis and necrosis) and compared the results to a reference oxidant vitamin E. RESULTS The determination of total phenol extracts of HHL was 59.91 ± 0.35 mg of Gallic Acid/g dry plant material with higher antioxidant activity (91.73% ± 1.67) compared to vitamin E (87.42%). Using aqueous extract of HHL, we noted a significant decrease of AST and ALT [1129 UI (585/1995) and 768 UI (335/1375)] compared to no-treated group [5,585.5 UI (5,035/12,070) and 8,099.5 UI (5,040/12,326)] as a decrease in MDA content [85.7% protection (50.9/91.5)]. HHL extract reduce the damage induced by I-R of 48.7% (27/48.7) and 96.1% (95.7/96.5) for necrosis and apoptosis lesions respectively. CONCLUSION HHL aqueous extract have potential to protect liver from the damage effect induced by I-R better than vitamin E solution.INTRODUCTION Effective prevention strategies require specific actions during the different phases of ischemia-reperfusion (I-R) injury. The objective of our study is to evaluate the effect of aqueous extract of Hypericum humifusum leaves (HHL) on liver I-R model in Rat. MATERIAL AND METHODS Animals were subjected to 90 min of hepatic ischemia followed by reperfusion (120 min). HHL extract (25 mg/mL/kg) was injected 15 min before reperfusion. To evaluate the effect of HHL extract on I-R, we have monitored transaminases levels, Malondialdehyde (MDA) concentration, histological lesions (apoptosis and necrosis) and compared the results to a reference oxidant vitamin E. RESULTS The determination of total phenol extracts of HHL was 59.91 ± 0.35 mg of Gallic Acid/g dry plant material with higher antioxidant activity (91.73% ± 1.67) compared to vitamin E (87.42%). Using aqueous extract of HHL, we noted a significant decrease of AST and ALT [1129 UI (585/1995) and 768 UI (335/1375)] compared to no-treated group [5,585.5 UI (5,035/12,070) and 8,099.5 UI (5,040/12,326)] as a decrease in MDA content [85.7% protection (50.9/91.5)]. HHL extract reduce the damage induced by I-R of 48.7% (27/48.7) and 96.1% (95.7/96.5) for necrosis and apoptosis lesions respectively. CONCLUSION HHL aqueous extract have potential to protect liver from the damage effect induced by I-R better than vitamin E solution.

Convulsion tardive après instillation de lidocaïne pour bronchoscopie

INTRODUCTION Lidocaine toxicity usually appears rapidly and is directly correlated with plasma concentrations of the drug. CASE REPORT We report a case of a late neurologic toxicity occurring after instillation of lidocaine during fibre-optic bronchoscopy. A patient with bronchiolitis obliterans underwent a diagnostic bronchoscopy. She received multiples instillations of Xylocaine(®) 2% (lidocaine). Three and a half hours later, she had a tonic-clonic seizure. Seven hours later, this recurred. Lidocaine plasma levels were in the toxic range at the time of the first seizure (18.32μg/mL) with a significant decrease in the concentration noted 24hours later. CONCLUSION The slow absorption of lidocaine into the blood from the bronchial tree explains the delayed neurologic toxicity. Our observation is a reminder that complications can occur due to high doses of lidocaïne administrated by instillation. Thus, if the recommended dose of lidocaine is exceeded, it is essential to monitor patients closely for a prolonged period, especially those with fibrosing lung disease in order to avoid possible late toxicity.

Contribution of Therapeutic Monitoring in the Assessment of Toxic Adverse Effects of Mitotane: a Case Report

Mitotane provided serious side effects and low doses seemed to be tolerated. Determination of mitotane concentration in plasma is recommended. We report the case of toxic plasma levels with low doses of mitotane in a 47-year-old man with adrenocortical cancer.