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.

Inadvertent sulfonylurea-induced hypoglycemia. A dangerous, but preventable condition.

Two patients with severe hypoglycemia due to inadvertent use of oral hypoglycemic agents are described. Unintentional substitution of tablets with sulfonylurea drugs was related in both cases to a similarity in shape and color of the pills. In one case glyburide was interchanged with an artificial sweetener, while in the other case chlorpropamide was dispensed by a pharmacist instead of quinidine bisulfate. To our knowledge, 20 similar cases have been reported in the medical literature. Most of them were attributed to sound-alike trade names of drugs. Inadvertent sulfonylurea-induced hypoglycemia has to be included in the differential diagnosis of severe unexplained hypoglycemia. This dangerous condition can be prevented by instructing patients to carefully identify their drugs, introducing typed prescription forms using generic names, and avoiding similar names and appearance of pills.

Encephalopathy induced by oral hypoglycemic drugs.

Three patients experienced severe hypoglycemic encephalopathy during oral therapy of adult-onset diabetes mellitus. Disabling residual neurological deficits were observed in two of these patients. The insidious time course of drug-induced hypoglycemia appeared to prevent patient recognition of sustained hypoglycemia. These cases indicate the need for further caution in the administration of oral hypoglycemic agents.

Sulfonylurea-induced factitious hypoglycemia. A growing problem.

Two patients had sulfonylurea-induced factitious hypoglycemia. Both patients demonstrated hyperinsulinism during hypoglycemia suggesting the presence of an insulin-secreting tumor. One patient underwent an exploratory laparotomy with subtotal pancreatectomy before the etiology of the hypoglycemia was discovered. Inboth patients, the diagnosis was made by detecting sulfonylurea agents in blood. A survey of Portland, Ore metropolitan hospitals suggests that factitious hypoglycemia occurs with a frequency similar to the insulinoma syndrome. The biochemical similarity of these disorders and the apparent increasing incidence of factitious hypoglycemia suggests that blood determinations of sulfonylurea agents should be performed prior to exploratory laparotomy for an insulinoma.

Hypoglycemic coma, jaundice, and pure RBC aplasia following chlorpropamide therapy.

Five weeks following the initiation of chlorpropamide therapy for diabetes mellitus, hypoglycemic coma, cholestatic jaundice, and RBC aplasia developed in a 41-year-old woman. Within 40 days of stopping the drug, she had made a complete recovery. To our knowledge, this is the first case in which these three complications of chlorpropamide have occurred simultaneously.

Chlorpropamide-induced optic neuropathy.

A 65-year-old woman with adult-onset diabetes treated with chlorpropamide (Diabenese) had a toxic optic neuropathy that resolved with discontinuation of chlorpropamide therapy. Visual loss occurs in diabetics for a variety of reasons, and accurate diagnosis is necessary to institute appropriate therapy. The possibility of a drug-induced optic neuropathy should be considered in the differential diagnosis of visual loss in diabetics.

The significance of the cerebrospinal fluid examination in the management of chlorpropamide-induced hypoglycemia.

Chlorpropamide-induced hypoglycemia is often overlooked, misdiagnosed, and mistreated, because of the atypical, insidious, and intermittent clinical picture and because of the normal serum glucose level in some of the patients when arriving at the hospital. These facts are demonstrated in three case reports. Since the correction of low glucose levels in the cerebrospinal fluid occurs hours after its correction in the serum, examining and at times following the cerebrospinal fluid glucose levels in patients with chlorpropamide-induced neuroglycopenia will enable physicians to diagnose and cure more patients. A high index of suspicion should exist in the presence of any atypical encephalopathy, mainly in the elderly diabetic patient treated with chlorpropamide and suffering from impaired cerebral, hepatic, or renal function. By suspecting and identifying neuroglycopenia, disabling residual deficits and even death could eventually be prevented.

Chlorpropamide-induced hyponatremia: incidence and risk factors.

The incidence and risk factors of chlorpropamide-induced hyponatremia were assessed in diabetic outpatients. In 176 chlorpropamide-treated patients, 11 (6.3%) exhibited hyponatremia (serum sodium less than or equal to 129 meq/L) during the mean follow-up period of 7.4 yr. In contrast, only one (0.6%) developed hyponatremia in 162 tolbutamide- or glibenclamide-treated patients (P less than 0.005). Moreover, administration to elderly patients and combination with thiazide diuretics were regarded as significantly potent risk factors for the development of hyponatremia in patients receiving chlorpropamide.

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.

Chlorpropamide-induced hyponatremia.

A 29-year-old woman with severe idiopathic diabetes insipidus, while being treated by a combination of chlorpropamide and chlorothiazide, developed the syndrome of inappropriate secretion of ADH (SIADH) following an overdose of chlorpropamide. The syndrome resolved as the serum chlorpropamide level fell. This report demonstrates that a chlorpropamide-induced SIADH can occur in a patient with idiopathic diabetes insipidus, and it appears that the antidiuretic effect of the drug is dose-related.

Profound hypoglycemia with the addition of a tricyclic antidepressant to maintenance sulfonylurea therapy.

Cases of profound hypoglycemia after the initiation of tricyclic antidepressant therapy in two patients taking sulfonylureas are described. To the authors' knowledge, this is the first report of a potential drug interaction between tricyclic antidepressants and sulfonylureas.

Association of hyperinsulinemia with chlorpropamide toxicity.

Clinical and metabolic features of chlorpropamide toxicity are described in two patients with diabetes mellitus and accidental chlorpropamide overdosage. Elevated serum insulin levels were found during hypoglycemia in both patients. The world's literature was reviewed for other cases of chlorpropamide toxicity in which insulin levels have been measured during hypoglycemia. A consistent feature of chlorpropamide toxicity is hyperinsulinemia. It is concluded that stimulation of the pancreatic beta cells during chlorpropamide toxicity leads to hyperinsulinemia and hypoglycemia.

Nephrotic syndrome and immune complex glomerulonephritis associated with chlorpropamide therapy.

Therapeutic drugs are well-recognized as a cause of the nephrotic syndrome in humans. However, documentation of the renal histopathologic features is lacking or incomplete in many cases. Even when accurate histopathologic information is available, there is little evidence to support a specific pathogenetic mechanism of renal injury in the vast majority of cases. We describe a patient with diabetes who had hepatitis and dermatitis in association with the use of chlorpropamide. In addition to these well-described toxic reactions to this drug, the nephrotic syndrome developed. Renal biopsy revealed the presence of a proliferative glomerulonephritis that was shown to be of an immune complex nature on immunofluorescence and electronmicroscopic study. Serial serum complement levels and circulating immune complex levels were consistent with an immunologically mediated reaction. Repeated renal biopsy documented resolution of the renal changes. Thus, in this patient, a drug-induced nephrotic syndrome was associated with a proliferative glomerulonephritis, probably due to the formation of immune complexes.

Treatment strategies for patients with non-insulin-dependent diabetes mellitus.

Strategies for the treatment of patients with non-insulin-dependent diabetes mellitus are discussed. In order to achieve treatment goals, diet and exercise remain important components of an overall treatment program that may include sulfonylurea drugs, especially in cases where patients are of normal weight or only slightly obese, have had the disease less than five years, and are taking little or no insulin. Failure to control blood sugar levels with sulfonylurea drugs may lead to combining this therapy with insulin or administering insulin alone, regardless of patients' weights.

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.

Chlorpropamide-induced Syndrome of Inappropriate Antidiuretic Hormone Secretion.

The Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) is a rare but serious complication of chlorpropamide therapy. In 2 elderly women who had diabetes mellitus, the SIADH developed two months after the chlorpropamide dosage had been increased to 500 mg daily. The syndrome disappeared after withdrawal of the drug. In one of these patients, re-administration of chlorpropamide resulted in recurrence of the SIADH. A review of the current literature disclosed certain common denominators, i.e., most of the patients are elderly women whose dosage of chlorpropamide was increased shortly before the development of the SIADH.

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.

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.

Glyburide: a second-generation sulfonylurea hypoglycemic agent. History, chemistry, metabolism, pharmacokinetics, clinical use and adverse effects.

Glyburide, a second-generation hypoglycemic sulfonylurea, is 200 times as potent as tolbutamide. This increase is due to greater intrinsic hypoglycemic potency of the molecule rather than to a prolonged biologic half-life. Glyburide is inactivated by the liver to 4-trans-hydroxyglyburide and 3-cis-hydroxyglyburide; 50% of these compounds is excreted in the urine and 50% in the bile. Although the serum concentration of glyburide can be measured by radioimmunoassay and high-performance liquid chromatography, the importance of its serum concentration in the reduction of hyperglycemia is not yet established. Glyburide has a therapeutic effectiveness comparable to that of the first-generation sulfonylurea chlorpropamide; however, it has a lower frequency of adverse effects. To date it has a low frequency of clinically significant interactions with other drugs. Glyburide should not be prescribed for patients with liver disease or significant renal disease. Because glyburide is a potent hypoglycemic agent, it should be prescribed in small initial doses, particularly for elderly patients with diabetes. At the present time there is no definite evidence that it modifies the increased risk of cardiovascular disease of diabetic patients. Although glyburide is a potent stimulator of pancreatic insulin secretion after short-term administration, an additional mechanism of action during long-term administration is to decrease the resistance of muscle and liver to the action of insulin. It is a useful medication for patients with type II diabetes whose hyperglycemia is not adequately reduced by dietary management and exercise. It can be used as the initial drug in these patients or as the replacement drug for those with primary or secondary failure during therapy with first-generation sulfonylureas.

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.