Chaker Ben Salem

Drug-Induced Hypoglycaemia

Drugs are the most frequent cause of hypoglycaemia in adults. Although hypoglycaemia is a well known adverse effect of antidiabetic agents, it may occasionally develop in the course of treatment with drugs used in everyday clinical practice, including NSAIDs, analgesics, antibacterials, antimalarials, antiarrhythmics, antidepressants and other miscellaneous agents. They induce hypoglycaemia by stimulating insulin release, reducing insulin clearance or interfering with glucose metabolism. Several drugs may also potentiate the hypoglycaemic effect of antidiabetic agents. Administration of these agents to individuals with diabetes mellitus is of most concern. Many of these drugs, and depending on clinical setting, may also induce hyperglycaemia. Drug-induced hepatotoxicity and nephrotoxicity may lead in certain circumstances to hypoglycaemia. Some drugs may also induce hypoglycaemia by causing pancreatitis. Drug-induced hypoglycaemia is usually mild but may be severe. Effective clinical management can be handled through awareness of this drug-induced adverse effect on blood glucose levels. Herein, we review pertinent clinical information on the incidence of drug-induced hypoglycaemia and discuss the underlying pathophysiological mechanisms, and prevention and management.

Drug-Induced Hypokalaemia

Hypokalaemia (defined as a plasma potassium concentration<3.5 mEq/L) is a common electrolyte abnormality in clinical practice. Drugs are a common cause of either asymptomatic or symptomatic hypokalaemia. Drug-induced hypokalaemia is an important problem particularly in the elderly and in patients with cardiovascular, renal or hepatic disease. Hypokalaemia can complicate the use of the drug in the therapeutic concentration range, and can also be precipitated with overdose or conditions leading to drug intoxication. Because the etiologies of hypokalaemia are numerous, the diagnosis of drug-induced hypokalaemia may be overlooked. Physicians should always pay close attention to this common side effect. Evaluation and management of a hypokalaemic patient should include a careful review of medications history to determine if a drug capable of causing or aggravating this electrolyte abnormality is present.SummaryDrug-induced hypokalaemia is a widespread problem in the elderly that can be caused by many therapeutically useful substances, the most common of which are diuretics. In certain classes of patients (e.g. those with acute myocardial infarction, with congestive heart failure receiving digitalis, or with cirrhosis), iatrogenic hypokalaemia is an established risk factor. In patients with hypertension who have no underlying heart disease or liver disease, the use of diuretics may lead to worsened glucose tolerance and cardiac arrythmias. There is also evidence for an increased risk of sudden cardiac death.

Captopril-induced lichen planus pemphigoides

To report a rare case of lichen planus pemphigoides (LPP) possibly induced by captopril.

Severe Acute Pancreatitis Due to Tamoxifen-Induced Hypertriglyceridemia with Positive Rechallenge

CONTEXT Pancreatitis is a very rare adverse effect of tamoxifen with only six cases of tamoxifen-associated pancreatitis reported in the English literature until now. In these cases, rechallenge with tamoxifen was not carried out. CASE REPORT We report a case of recurrent severe acute pancreatitis in a 44-year-old female induced by tamoxifen therapy and review the literature with regards to tamoxifen-associated pancreatitis. CONCLUSION Clinicians should be aware of the risks of developing severe acute pancreatitis when using tamoxifen therapy. If tamoxifen is suspected as the probable causative agent, rechallenge with this drug should be prohibited.

Cytolytic Hepatitis Possibly Related to Levonorgestrel/Ethinylestradiol Oral Contraceptive Use: 2 Case Reports

This letter to the editor reports on two cases of biopsy-confirmed cytolytic hepatitis induced by a levonorgestrel/ethinylestradiol combination oral contraceptive pill.

Pioglitazone-Induced Acute Rhabdomyolysis

Pioglitazone, a peroxisome proliferator–activated receptor γ agonist, is a relatively new oral antidiabetes agent. It has been shown to decrease insulin resistance in patients with type 2 diabetes, resulting in lowered blood glucose concentrations and A1C values. It can be used alone or in combination with metformin or a sulfonylurea. The adverse effects of pioglitazone include weight gain, headache, and edema. We report here a case of a patient who developed severe acute rhabdomyolysis after receiving pioglitazone. A 52-year-old man had a 2-year history of type 2 diabetes that was treated with gliclazide (60 mg/day). Six weeks after addition for pioglitazone (15 mg/day), the patient was admitted to hospital for 4 …

Valproic acid-induced pancreatitis

biliary drainage followed by cholecystectomy and surgical removal of the stones from the common bile duct. Infl ammation in the biliary tract rapidly improved by this treatment without prolongation of hepatic dysfunction. The observation of portal tract obstruction led us to further analyze the blood fl ow via both the portal vein and hepatic artery by CT with angiography. At the onset, the main trunk of the portal vein was completely occluded (Fig. 1A) and portal supply was found only in the area close to the hepatic hilus (central zone) (Fig. 1B), whereas hepatic arterial fl ow spread throughout the entire area, and particularly in the peripheral zone of the liver (Fig. 1C). The remaining portal fl ow was not through the main trunk but via the collateral veins along the common bile duct (Fig. 1B). After 6 months of treatment, when portal blood fl ow was restored (Fig. 1D), the blood supply via the portal tract extended over the liver except in the peripheral area (Fig. 1E). In contrast, hepatic arterial fl ow had diminished and was found only in the peripheral zone of the liver (Fig. 1F). Therefore, the present case obviously showed a compensation balance between the portal and arterial blood streams (compare Fig. 1B and C; 1E and F). Moreover, we clearly demonstrated an alteration of the hepatic blood fl ow balance along with the restoration of the portal infl ux (compare Fig. 1B and E; 1C and F).

Fatal allopurinol-induced hypersensitivity syndrome associated with pancreatic abnormalities.

Allopurinol hypersensitivity syndrome is a severe adverse reaction characterized by rash, fever, and internal organ involvement. We report a case of fatal allopurinol-induced hypersensitivity syndrome associated with acute pancreatitis.A 46-year-old man was treated by allopurinol for asymptomatic hyperuricemia. The patient developed a diffuse erythrodermic maculopapular eruption and fever. Laboratory analysis revealed cytolysis and cholestasis, amylases and lipases were highly elevated. Computed tomography scans revealed pancreatitis Grade C. The treatment of asymptomatic hyperuricemia should only be initiated when there is a clear indication to reduce the incidence and the severe consequences of allopurinol hypersensitivity syndrome.

In silico screening and study of novel ERK2 inhibitors using 3D QSAR, docking and molecular dynamics

ERK2 is a dual specificity protein kinase, part of the Ras/Raf/MEK/ERK signal transduction cascade. It forms an interesting target for inhibition based on its relationship with cell proliferation and oncogenesis. A 3D QSAR pharmacophore model (Hypo1) with high correlation (r=0.938) was developed for ERK2 ATP site on the basis of experimentally known inhibitors. The model included three hydrogen bonds, and one hydrophobic site. Assessment of Hypo1 through Fisher randomization, cost analysis, leave one out method and decoy test suggested that the model can reliably detect ERK2 inhibitors. Hypo1 has been used for virtual screening of potential inhibitors from ZINC, Drug Bank, NCI, Maybridge and Chembank databases. Using Hypo1 as a query, databases have been interrogated for compounds who meet the pharmacophore features. The resulting hit compounds were subject to docking and analysis. Docking and molecular dynamics analysis showed that in order to achieve a higher potency compounds have to interact with catalytic site, glycine rich loop, Hinge region, Gatekeeper region and ATP site entrance residues. We also identified catalytic site and Glycine rich loop as important regions to bind by molecules for better potency and selectivity.

Methotrexate-Induced Papular Eruption Following Treatment of Psoriasis

Objective: To report a case of a diffuse papular eruption following treatment of psoriasis with methotrexate injections. Case Report: A 52-year-old woman presented with an extensive flare of psoriasis associated with joint pain, especially in her knees and elbows. She was treated with intramuscular injections of methotrexate 20 mg/wk. Ten hours after the second methotrexate injection, the patient experienced a diffuse pruritic papular eruption located mainly on the limbs. Histology showed foci of dyskeratosis in the mucosal layer and a polymorphic perivascular inflammatory infiltrate of (he papillary dermis, suggesting a drug-induced skin reaction. According to the Naranjo probability scale, the papular eruption was probably caused by methotrexate. The drug was discontinued and papular lesions gradually disappeared. Discussion: Methotrexate-induced papular eruption is rarely reported shortly after beginning methotrexate therapy in patients with acute exacerbation of collagen vascular diseases. Methotrexate-induced papular eruption following treatment of psoriasis has not been previously reported. Conclusions: The pathogenesis of methotrexate-induced papular eruption in collagen vascular diseases may suggest cutaneous small-vessel vasculitis. In our patient, histology showed aspects of drug-Induced skin reaction without vasculitis. Pathogenesis of methotrexate-induced papular eruption in psoriasis may Involve immune mechanisms other than those of methotrexate-induced cutaneous vasculitis in collagen vascular disease.