HYPOGLYCEMIA INDUCED BY ANTIDIABETIC SULFONYLUREAS.

Diabetes mellitus is a major health problem due to its increasing prevalence and life-threatening complications. Antidiabetic sulfonylureas represent the first-line drugs in type 2 diabetes even though the most common associated risk is pharmacologically-induced hypoglycemia. In the development of this side effect are involved several factors including the pharmacokinetic and pharmacodynamic profile of the drug, patient age and behavior, hepatic or renal dysfunctions, or other drugs associated with a high risk of interactions. If all these are controlled, the risk-benefit balance can be equal to other oral antidiabetic drugs.

Oral lichenoid drug reaction associated with antihypertensive and hypoglycemic drugs.

Oral lichen planus and oral lichenoid drug reactions have similar clinical and histologic findings. The onset of oral lichenoid drug reactions appears to correspond to the administration of medications, especially antihypertensive drugs, oral hypoglycemic drugs, antimalarial drugs, gold salts, penicillamine and others. The author reports the case of 58-year-old male patient with oral lichenoid drug reaction, hypertension and diabetes mellitus. The oral manifestation showed radiated white lines with erythematous and erosive areas. The patient experienced pain and a burning sensation when eating spicy food. A tissue biopsy was carried out and revealed the characteristics of lichen planus. The patient was treated with 0.1% fluocinolone acetonide in an orabase as well as the replacement of the oral hypoglycemic and antihypertensive agents. The lesions improved and the burning sensation disappeared in two weeks after treatment. No recurrence was observed in the follow-up after three months.

Síndrome de secreción inadecuada de hormona antidiurética por tratamiento con clorpropamida / Syndrome of inappropriate secretion of antidiuretic hormone due to treatment with chlorpropamide

La clorpropamida es un antidiabético oral cuyo uso se ha asociado a la producción de hiponatremia y síndrome de secreción inadecuada de ADH (SIADH). Es un fármaco que va quedando cada vez más relegado, debido a sus efectos secundarios; sin embargo, conviene conocerlos, ya que todavía no es infrecuente encontrar a pacientes, fundamentalmente ancianos, en tratamiento con este fármaco. Se describe un nuevo caso de SIADH asociado a la utilización de clorpropamida

Chlorpropamide is an oral antidiabetic agent whose use has been associated to production of hyponatremia and syndrome of inappropriate secretion of antidiuretic hormone (SISAH). This is a drug that is being used increasing less due to its side effects. However, it is important to know them because it is not infrequent to find patients, basically the elderly, who are being treated with this drug. A new case of SISAH associated to the use of chlorpropamide is described

The effect of deinsuring chlorpropamide on the prescribing of oral antihyperglycemics for Nova Scotia Seniors' Pharmacare beneficiaries.

On behalf of the Nova Scotia Seniors' Pharmacare Program, the Drug Evaluation Alliance of Nova Scotia developed a multicomponent intervention plan to facilitate the removal of chlorpropamide as an insured benefit. Chlorpropamide has caused serious hypoglycemia in seniors to a greater extent than some other agents. Pharmacy administrative claims were used to compute monthly use rates for insulin and each oral antihyperglycemic drug from January 1, 2000-December 30, 2002, in an intervention cohort (patients receiving chlorpropamide) and a control cohort (patients receiving an antihyperglycemic agent other than chlorpropamide). Initially, 630 patients were receiving chlorpropamide therapy. By the time chlorpropamide was deinsured, only 10% of the treatment cohort continued receiving chlorpropamide; shortly after deinsurance, no beneficiaries continued receiving the drug. The antihyperglycemics with the greatest increase in prescription were glyburide and gliclazide. The deinsuring of chlorpropamide and the educational strategies that accompanied it resulted in the selection of more appropriate antihyperglycemics for Nova Scotia seniors.

The advantages and disadvantages of a 'herbal' medicine in a patient with diabetes mellitus: a case report.

BACKGROUND: Patient-initiated alternative treatments in the management of chronic conditions are common and increasing in the United Kingdom. To date, there have been no reports of herbal medicine use alone in the management of diabetes mellitus. We report here the case of a man who attained excellent glycaemic control using a 'herbal' medicine and reveal how important it was to identify the products of active constituents. CASE REPORT: A 48-year-old man attending our clinic in Tooting, South London with known Type 2 diabetes, with evidence of both micro- and macro-vascular diabetes-related complications, was poorly controlled despite a drug regimen consisting of oral metformin and twice daily insulin. He went to India for at least 1 year and on returning to the clinic had excellent glycaemic control off all diabetic medication. While away he had started himself on a regimen of three different 'herbal' balls. Samples of blood were found to contain chlorpropamide in a therapeutic concentration; chlorpropamide was also found in one of the balls. He has been counselled on the potential risks associated with chlorpropamide and his treatment reverted to a more conventional treatment regimen. CONCLUSIONS: General practitioners and hospital physicians should be alert to those patients returning from abroad on effective 'herbal' medications that these may in fact contain an active ingredient.

Effect of the chlorpropamide and fructose-1,6-bisphosphate of soluble TNF receptor II levels.

Inflammatory cytokines are central to the pathogenesis of septic shock, and future therapies will depend on interfering with the effects of these cytokines. The aim of this study was to investigate the effect of the two drugs, Fructose-1,6-bisphosphate (FBP), a high-energy glycolytic pathway intermediate, and chlorpropamide (sulfonylurea) on proliferation of T-lymphocytes and on the levels of soluble receptors of tumor necrosis factor (sTNFRII). Peripheral blood mononuclear cells (PMBCs) were isolated from the blood of healthy humans by gradient centrifugation. T-lymphocytes were stimulated for 96h with phytohemagglutinin (PHA) and varying concentrations of chlorpropamide and FBP. They were stimulated for 24h with lipopolysaccharide (LPS) and varying concentrations of chlorpropamide and FBP were used. Chlorpropamide at concentrations between 2.5 and 10mM and FBP at concentrations between 1.25 and 10mM decreased proliferation of T-lymphocytes. The chlorpropamide reduced the viability only at a concentration of 10mM and FBP at concentrations of 5.0 and 10mM. The levels of sTNFRII were reduced at chlorpropamide concentrations between 2.5 and 5mM and FBP between 1.25 and 2.5mM. In conclusion, our results suggest that FBP acts, as does chlorpropamide, to inhibit the cellular proliferation and thereby reducing the sTNFRII levels through blockage of the potassium channels. In this way it acts as a powerful immunomodulatory agent.

Agentes antidiabéticos orales / Oral antidiabetical agents

El presente artículo describe los diferentes agentes antidiabéticos orales utilizados con frecuencia en casos de diabetes mellitus Tipo II. Se detalla su acción terapéutica, modos de acción y efectos colaterales y adversos (AU)

Tratamiento de liquen plano con griseofulvina / Treatment of lichen planus with griseofulvin

Presentamos un paciente de sexo masculino, de 15 años de edad, con diagnóstico clínico e histopatológico de liquen plano. Fue tratado con griseofulvina 500 mg/día y fenoxifenadina 120 mg/día con mejoría tanto subjetiva como objetiva al cabo del mes de tratamiento. Se confirma la griseofulvina como alternativa terapéutica para el liquen plano (AU)

A systematic review of drug induced ocular reactions in diabetes.

AIMS: To conduct a systematic review of drug induced adverse ocular effects in diabetes to determine if this approach identified any previously unrecognised adverse drug effects; to make a preliminary assessment of the feasibility of this approach in identifying adverse drug reactions; and to assess the current accessibility of this information to prescribing physicians. METHODS: Literature search of online biomedical databases. The search strategy linked eye disorders with adverse drug reactions and diabetes. Source journals were classified as medical, pharmaceutical, diabetes related, or ophthalmological. It was determined whether the reactions identified were recorded in drug datasheets and the British National Formulary. RESULTS: 63 references fulfilled the selection criteria, of which 45 were considered to be relevant to the study. The majority of these were case reports but cross sectional surveys, case-control and cohort studies, and review articles were also identified. 61% of the reactions were not recorded in the British National Formulary and 41% were not recorded in the datasheets. 55% appeared in specialist ophthalmology journals. CONCLUSIONS: This is a feasible approach to the identification of adverse drug reactions. Adverse reactions not listed in the most commonly used reference sources were found. The majority were published in specialist ophthalmology journals which might not be seen by prescribing physicians.

Rates of hypoglycemia in users of sulfonylureas.

OBJECTIVE: To identify the demographic and clinical characteristics of sulfonylurea users. To assess the risk of hypoglycemia in patients treated with sulfonylureas in clinical practice, and to characterize the risk in relation to the different drugs used. RESEARCH DESIGN AND METHODS: A cohort of 33,243 sulfonylurea users chosen from 719 clinical practices in the United Kingdom were identified through the VAMP-Research database. Information on demographic characteristics, medical diagnoses and use of medical services was obtained through the computerized records. For a stratified sample of 500 patients, general practioners completed a structured questionnaire on the duration, treatment, and complications of diabetes mellitus, obesity, alcohol use, and smoking history. Patients with a diagnosis of hypoglycemia, as recorded in the database within a time-window of a sulfonylurea prescription, were identified. Incidence rates per person-year of sulfonylurea therapy were estimated. RESULTS: Other than a longer duration of diabetes in users of chlorpropamide, no differences were observed among users of different sulfonylurea agents with respect to diabetic complications, adequacy of diabetic control, obesity, smoking, and excessive alcohol consumption. A diagnosis of hypoglycemia during sulfonylurea therapy was recorded in 605 people over 34,052 person-years of sulfonylurea therapy, which converted into an annual risk of 1.8%. The risk in glibenclamide users was higher than in users of other types of sulfonylureas uses. Duration of therapy, concomitant use of insulin, sulfonylurea-potentiating or antagonizing and concomitant use of beta-blockers were predictive of the risk of developing hypoglycemia. DISCUSSION: Drug use patterns showed comparability among users of different sulfonylurea agents. Our findings suggest that the rate of diagnosis of hypoglycemia made by physicians is higher for glibenclamide than for other sulfonylureas. An epidemiological study with objectively diagnosed hypoglycemia should be undertaken to confirm these results.

Photohemolytic potency of oral antidiabetic drugs in vitro: effects of antioxidants and a nitrogen atmosphere.

The sulphonamide-derived oral antidiabetic drugs carbutamide, chlorpropamide, glibenclamide, glibornuride, gliclazide, glipizide, gliquidone, glisoxepide, glymidine, tolazamide and tolbutamide were investigated for photohemolytic properties in vitro. Irradiation with a SOL 3 apparatus (solar simulating irradiation) revealed hemolysis in the presence of chlorpropamide, glipizide, gliquidone, glymidine and tolbutamide (all in the concentration 10(-3) mol/l). Except for glymidine, which exerted photohemolysis in the concentration 10(-4) mol/l, no hemolytic effects were seen in the concentration of 10(-4) mol/l or 10(-5) mol/l. Irradiation with TL 12 light bulbs (UVB), a UVASUN 5000 apparatus (UVA) or an experimental lamp (visible light) did not induce phototoxic hemolysis with either of the test substances. Addition of the antioxidants ascorbic acid, alpha-tocopherol or superoxide dismutase significantly inhibited the phototoxic hemolysis. Investigations carried out in a nitrogen-rich atmosphere reduced the hemolysis as well. These findings indicate an involvement of reactive oxygen species in the mechanism of action of the hemolytic process in the presence of oral antidiabetic drugs.

Chlorpropamide-induced ADH release, hyponatremia and central pontine myelinolysis in diabetes mellitus.

Chlorpropamide (CPM) has been reported to produce impaired water excretion due to the enhancement of renal vasopressin (ADH) action and/or due to centrally enhanced ADH release, but it is still unknown whether CPM gives rise to ADH release with a subsequent hyponatremia in diabetes mellitus (DM), which, in turn, causes an impairment of the central nervous system. In 3 patients with DM, who developed hyponatremia during the treatment with CPM, an acute water load (WL) was carried out in the presence and absence of the drug, and plasma ADH was determined with plasma and urine osmolalities. Moreover, in 2 cases, MRI scans of the brain were taken. In all the patients, acute WL tests failed to suppress completely ADH release in response to changes in plasma osmolality in the presence of CPM, which, in turn, resulted in the impaired water excretion. In the absence of CPM, an acute WL normally suppressed plasma ADH leading to the diuresis. MRI scans illustrated the presence of central pontine myelinolysis. It is likely that CPM might stimulate ADH release in DM with a subsequent hyponatremia and brain damages.

Closet hypoglycemia.

An elderly nondiabetic woman was found stuporous and unresponsive at home. In the emergency department, testing revealed that she had a serum glucose of 40 mg/dL (2.2 mmol/L). No underlying metabolic cause could be determined. An inspection of her medications disclosed a professional medication sample bottle labeled as containing a nonsteroidal anti-inflammatory drug (NSAID) that actually contained chlorpropamide tablets. Drugs, notably sulfonylureas, must be considered as a possible cause of unexplained severe hypoglycemia.

Hypertension secondary to chlorpropamide with amelioration by changing to insulin.

A retrospective analysis of the records of 22 type II diabetics whose treatment had been changed from insulin to chlorpropamide was performed to investigate the relative effects of insulin and chlorpropamide on blood pressure. Although diastolic BP index was not significantly different between the treatments, systolic BP index was significantly higher on chlorpropamide than on insulin (141 +/- 3 v 135 +/- 3 mm Hg, P = .02). In 10 patients in whom insulin was reinstituted, systolic BP fell significantly (P < .005), suggesting that in type II diabetics chlorpropamide exerts a relative hypertensive effect in comparison to insulin.