Drug-induced Hypoglycemia Research Articles

Glucose concentration-dependent potentiation of insulin secretion by a new chemical entity, KCP256

The insulinotropic activity of KCP256 [( R)-8-benzyl-2-cyclopentyl-7, 8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride] was examined using MIN6 cells (a pancreatic β-cell line) and pancreatic islets isolated from rats. Unlike sulfonylurea anti-diabetic drugs, KCP256 dose-dependently (0.1–10 μM) enhanced insulin secretion from MIN6 cells and its insulinotropic effect was exerted only at high concentrations of glucose (8.3–22 mM) but not at low concentrations of glucose (3.3–5.5 mM). Furthermore, the action mechanism of KCP256 was different because, unlike sulfonylurea drugs, KCP256 did not displace the binding of [ 3H]glibenclamide, and did not inhibit the 86Rb + efflux nor K ATP channel activity. In isolated islets, KCP256 also enhanced insulin secretion in a dose- and a glucose-concentration-dependent manner. Plasma levels of insulin after glucose challenge in KCP256-administrated rats were higher than those in vehicle-administrated animals, indicating that KCP256 can enhance insulin secretion in vivo. Since the insulinotropic activity of KCP256 only occurs at high concentrations of glucose, this novel drug may exhibit a decreased risk of drug-induced hypoglycemia compared with sulfonylurea drugs when treating patients with diabetes.

Confusion, Somnolence, Seizures, Tachycardia? Question Drug-induced Hypoglycemia

Confusion, Somnolence, Seizures, Tachycardia? Question Drug-induced Hypoglycemia

Drug-induced hypoglycemia

Hypoglycemia is a clinical syndrome with diverse causes in which low levels of plasma glucose eventually lead to neuroglycopenia. Hypoglycemia is the most common endocrine emergency faced by practicing physicians. Though hypoglycemia is a very common medical problem both in adults and children seeking medical help, most of it is introgenic. Treatment with oral hypoglycamic agents, alone or in combination, and/or insulin is an ongoing threat for diabetic patients and still accounts for the majority of cases of hypoglycemia. Numerous other drugs have been reported to induce hypoglycemia, sometimes in seemingly healthy individuals in whom it may masquerade as spontaneous hypoglycemia. Predisposing lactors to drug-induced hypoglycemia include restricled carbohydrate intake, extremes of age and abnormal liver and kidney function to drug-induced hypoglycemia, the offending drug should be eliminated immediately and patients should receive other supportive measures to raise and maintain blood sugar levels. It is also important to avoid future recurrences. Enhanced therapeutic monitoring may be warranted when drugs with hypoglycamic potential are administered. The risk for possible drug interactions that may cause hypoglycemia increases exponentially as the number of medications in a patient's regiman increases. Although most physicians are familiar with the treatment of hypoglycemie, appropriate evaluation and follow-up of the problem require knowledge of several relatively rare diagnostic considerations.

Severe hypoglycemia in an elderly patient treated with metformin

The following case of severe hypoglycemia was reported during a systematic evaluation of hospital admissions caused by adverse drug reactions (supported by BfArM). A 79-year-old diabetic woman was admitted to hospital in a stuporous and unresponsive state. The initial physical examination revealed no other abnormal findings. Serum blood glucose was found to be 2.0 mmol/l and HbA1c was 4.6%. The patient had been started on antidiabetic therapy with metformin 2 months earlier. Treatment with other drugs being taken at that time, an ACE inhibitor, an NSAID and nitrofurantoin, remained unchanged. DIAGNOSIS, TREATMENT AND FOLLOW-UP: Laboratory tests excluded lactic acidosis and renal insufficiency. Cerebral computed tomography findings were normal. The patient improved dramatically following administration of glucose. Other laboratory findings confirmed the diagnosis of hypoglycemia. Blood glucose concentrations ranged between 4.0 and 10.0 mmol/l in the subsequent days and the patient could be discharged in full health. Drug-induced hypoglycemia is possible even in diabetics not receiving insulin or oral antidiabetic agents increasing insulin secretion. The risk of drug-induced hypoglycemia should be particularly considered when drugs containing blood glucose-lowering components are combined. Metformin does not usually cause hypoglycemia when administered as monotherapy. We suspected that hypoglycemia in this patient was caused by additional blood glucose-lowering effects of the ACE inhibitor and the NSAID possibly combined with a suboptimal nutrition. The indications for metformin administration undergo critical scrutiny.

Management of type 2 diabetes mellitus in the elderly: special considerations.

The principles of managing type 2 diabetes mellitus in the elderly are no different from those in younger patients, but the priorities and therapeutic strategies need to be cautiously individualised. The objectives of treatment are to improve glycaemic control in a stepwise approach that involves nonpharmacological methods including diet and exercise, and pharmacological therapy including mixtures of oral antihyperglycaemic agents alone or in combination with insulin. Although the goals of treatment may be the same for elderly and younger patients, certain aspects of type 2 diabetes in the elderly require special consideration. Treatment decisions are influenced by age and life expectancy, comorbid conditions and severity of the vascular complications. Adherence to dietary therapy, physical activity, and medication regimens may be compromised by comorbid conditions and psychosocial limitations. Drug-induced hypoglycaemia has been the main consideration and the most serious potential complication. In addition, the long term macrovascular and microvascular complications of type 2 diabetes are a source of significant morbidity and mortality. Indeed, vascular and neuropathic complications are already present at the time of diagnosis in a significant number of patients, and the impact of improved diabetes control depends on the age and life expectancy of the patient. Age-related changes in pharmacokinetics and the potential for adverse effects and drug interactions should also be considered when choosing appropriate pharmacological therapy. In general, a conservative and stepwise approach to the treatment of the elderly patient with type 2 diabetes is suggested; treatment may be initiated with monotherapy, followed by early intervention with a combination of oral agents including a sulphonylurea as a foundation insulin secretagogue in addition to a supplemental insulin sensitiser. Insulin therapy is eventually required if significant hyperglycaemia [glycosylated haemoglobin (HbA1c) >8%] persists despite oral combination therapy. Combination therapy with evening insulin and a long-acting sulphonylurea such as glimepiride is an effective strategy to improve hyperglycaemia in the elderly patient with type 2 diabetes in whom polypharmacy with oral agents is unsuccessful. In addition, such a regimen is simple to follow for the patient who may not be able to adhere to a more complicated insulin regimen. Hyperglycaemia in the elderly can be managed well with practical intervention and a straightforward treatment plan to enhance compliance. Optimal glycaemic control should be possible for every patient if treatment is individualised; however, strict glycaemic control may not be achievable in all patients or even desirable in many elderly patients.

Trimethoprim-Sulfamethoxazole-Induced Hypoglycemia as a Cause of Altered Mental Status in an Elderly Patient

Drug-induced hypoglycemia is an important consideration in the differential diagnosis of altered mental status, especially in the elderly patient. Symptoms can be insidious, causing subtle mental status changes. In addition to the well known hypoglycemic effects associated with treatment of diabetes mellitus, several commonly prescribed medications, such as thiazides, sulfonylureas, and. some antibiotics, can cause hypoglycemia. We describe a case of hypoglycemia in an elderly patient taking sulfonamide antibiotics. Previous reports in the medical literature have described this occurrence with sulfonamides, all in renally impaired patients or in those who were also taking sulfonylurea drugs. Although the incidence of drug-induced hypoglycemia is rare in the general population, its incidence is not uncommon in elderly and diabetic patients.

HYPOGLYCEMIA IN PATIENTS WITH RENAL FAILURE

Of a total of 1545 admissions of end stage renal failure (ESRD) patients, fifty-six (3.6%) were admitted during a ten-year period with hypo glycemia. Thirty-eight of them were diabetic while the others were non-diabetic patients. The most common etiology found to be drug-induced hypoglycemia in 26 (46%) patients. In 22 (39%) cases, sepsis was the contributing cause of hypoglycemia. Severe malnutrition caused 7% of hypoglycemic episodes. Of the patients, 18 (32%) with ESRD eventually died, none of them were from the drug induced group. However, mortality rate in the sepsis induced hypoglycemia group was 66% and of the malnutrition group 17% of the deaths. Thus, hypoglycemia is frequent in ESRD patients, and is fatal if associated with either sepsis or malnutrition.

Drug-induced hypoglycemia in home care patients with diabetes

Although $1 of every $7 spent on health care in the United States is spent on diabetes, only one-third of the 16 million patients with diabetes have completed a diabetes education program. 1 Caregivers in home care settings have an opportunity to educate these patients and help identify and prevent drug-related problems, especially hypoglycemia.

Drug-induced hypoglycaemia

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Sulphonylurea‐induced hypoglycaemia in elderly people with diabetes

Practical Diabetes InternationalVolume 11, Issue 3 p. 102-103 Review ArticleFree Access Sulphonylurea-induced hypoglycaemia in elderly people with diabetes IW Campbell FRCP(Ed), Corresponding Author IW Campbell FRCP(Ed) Consultant Physician n/a@dne.dne Victoria Hospital, KirkcaldyCorrespondence to: Dr IW Campbell, Diabetic Department, Victoria Hospital, Kirkcaldy, Fife KY2 5AHSearch for more papers by this authorJ Chalmers MRCP(UK), J Chalmers MRCP(UK) Research Fellow Victoria Hospital, KirkcaldySearch for more papers by this authorOM Herlihy MB BCh(IRL), OM Herlihy MB BCh(IRL) Medical Registrar Victoria Hospital, KirkcaldySearch for more papers by this author IW Campbell FRCP(Ed), Corresponding Author IW Campbell FRCP(Ed) Consultant Physician n/a@dne.dne Victoria Hospital, KirkcaldyCorrespondence to: Dr IW Campbell, Diabetic Department, Victoria Hospital, Kirkcaldy, Fife KY2 5AHSearch for more papers by this authorJ Chalmers MRCP(UK), J Chalmers MRCP(UK) Research Fellow Victoria Hospital, KirkcaldySearch for more papers by this authorOM Herlihy MB BCh(IRL), OM Herlihy MB BCh(IRL) Medical Registrar Victoria Hospital, KirkcaldySearch for more papers by this author First published: 01 May 1994 https://doi.org/10.1002/j.1528-252X.1994.tb00019.xCitations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1Berger W. Incidence of severe side-effects during therapy with sulphonylureas and biguanides. Horm Metab Res 1985; 15(Suppl): 111– 5 2Campbell IW. Metformin and the sulphonylureas: the comparative risk. Horm Metab Res 1985; 15(Suppl): 105– 11 3Gerich JE. Oral hypoglycemic agents. N Engl J Med 1989; 34: 1231– 15 4Jennings AM, Wilson RM, Ward JD. Symptomatic hypoglycemia in NIDDM patients treated with oral hypoglycemic agents. Diabetes Care 1989: 12: 203– 8 5Ferner RE. Oral hypoglycemic agents. Med Clin North Am 1988; 72: 1323– 55 6Campbell IW. Hypoglycaemia and Type 2 diabetes: sulphonylureas. In: BM Frier, BM Fisher (eds). Hypoglycaemia and Diabetes. London: Edward Arnold. 1993. 387– 92 7Seltzer HS. Severe drug-induced hypoglycemia: a review. Comprehensive Therapy 1979; 5: 21– 9 8Palatrick W, Meaterall RC, Tenebein M. Clinical spectrum of sulfonylurea-overdose and experience with diazoxide therapy. Arch Intern Med 1991; 151: 1859– 62 9Marri G, Cozzolino G, Palumbo R. Glucagon in sulphonylurea hypoglycaemia. Lancet 1968: 1: 303– 4 10Asplund K, Wiholm B-E, Lithner F. Glibenclamide-associated hypoglycaemia: a report on 57 cases. Diabetologia 1983; 24: 412– 7 11Asplund K, Wiholm B-E, Lundman B. Severe hypoglycaemia during treatment with glipizide. Diabet Med 1991: 8: 726– 31 Citing Literature Volume11, Issue3May/June 1994Pages 102-103 ReferencesRelatedInformation

Self-Induced Insulin Hypoglycemia in a Bodybuilder

Hypoglycemia induced by self-administration of hypoglycemic drugs has occurred in diabetic patients, their relatives or friends, and in medical or paramedical personnel. Frequently, it occurs in young female individuals and is the result of a deliberate effort to create the impression of disease (factitious hypoglycemia) or is a suicide attempt. 1 The drugs more frequently used are sulfonylureas and insulin. In other cases, druginduced hypoglycemia had occurred by overdose or accidental intake of alcohol, propranolol, quinine, pentamidine, salicylate, and other substances. 2 More than 80% of the reported episodes of severe drug-induced hypoglycemia have occurred in acutely or chronically undernourished patients. Self-administration of insulin to achieve an anabolic effect in muscle is extremely unusual. However, it is well known that some athletes are capable of using drugs in an attempt to increase their muscle volume. 3 We describe a case of seizures in a male bodybuilder caused by self-administration of

The effect of tolbutamide on rat embryonic development in vitro.

Tolbutamide (TOLB) is a sulfonylurea used to treat non-insulin-dependent diabetes mellitus and is a suspected teratogen. However, it is not possible to discriminate between potential teratogenic effects of TOLB and malformations produced by either drug-induced hypoglycemia or the diabetic state itself. We examined the direct effect of TOLB on rat embryos cultured in a rodent whole embryo culture system. CD strain rat embryos were cultured for 48 h beginning on day 9 of gestation (plug day = day 0). Tolbutamide was added at various concentrations (90-3,600 microM). At the end of culture, viable embryos were examined for morphological score, number of somite pairs, crown-rump and head lengths, and DNA and protein content. Tolbutamide produced dose-related decreases in all endpoints at concentrations (2,250-3,600 microM) which are two to four times the human therapeutic concentration. Sera from TOLB-treated rats were adjusted to contain equal concentrations of glucose and insulin and then used for embryo culture. Serum from TOLB-treated rats had no observable effect on embryonic development. The mechanism for the embryotoxic effect of TOLB is unknown; however, the drug was previously demonstrated to alter activity of purified yeast glutathione reductase (GR). Because GR may be important for normal embryonic development, the effect of TOLB on this enzyme activity in cultured rat embryos was evaluated. Tolbutamide (2,700 microM) reduced embryonic GR activity by 35-57%. These results indicate that TOLB has a direct embryotoxic effect at levels 2 to 4 times the usual therapeutic serum concentrations on developing rodent embryos which may be mediated by GR inhibition.

Drug-Induced Hypoglycemia: A Review of 1418 Cases

The present review catalogues 1418 reported cases of drug-induced hypoglycemia. The main findings are that sulfonylureas (especially chlorpropamide and glyburide), either alone or with a second hypoglycemic or potentiating agent, still account for 63% of all cases; that alcohol, propranolol, and salicylate, either singly or with another hypoglycemic drug, are the next most frequent offenders (19% of the total); and that one older drug (quinine) and three new ones (pentamidine, ritodrine, and disopyramide) have caused an additional 7% of all episodes of severe hypoglycemia. The clinical factors that set the stage for drug-induced hypoglycemia are still restricted food intake, age, hepatic disease, and renal disease, both individually and even more so in combination. Drug-induced hypoglycemia continues to be so common that virtually every unconscious patient should be considered hypoglycemic until immediate estimation of the blood sugar level rules it in or out. If ruled in, the clinician should promptly start 10% intravenous glucose and plan to maintain it uninterruptedly for 1 or more days, with added glucagon, hydrocortisone, and diazoxide administration if necessary, until sustained hyperglycemia guarantees that all drug effects have worn off.

Drug-induced hypoglycaemia

Drug-induced hypoglycaemia

Calcium Infusion

Calcium gluconate (10 mg Ca(++)/kg) was administered intravenously over a 2-hour period to 16 adult patients who were evaluated for hypoglycemia. In nine of ten patients with benign or malignant insulinomas (eight proven at operation, and two with positive chemical tests and angiographic localization awaiting operation), significant hypoglycemia and hyperinsulinemia occurred within 60 to 90 minutes after the start of the calcium infusion. Serum proinsulin and Cpeptide concentrations increased at the time of the calciuminduced hyperinsulinemia in several patients in whom these parameters were studied. The one individual who did not respond to the calcium infusion was found to have a benign insulinoma. His basal glucose/insulin ratio of 0.64 was the lowest of the insulinoma group and thus his failure to respond to calcium may indicate that his tumor was secreting maximally at the time of the infusion. Following successful removal of the insulinoma, calcium infusion did not result in changes in serum glucose or insulin concentrations (tested in five patients). In contrast, neither a patient with pathologically documented islet cell hyperplasia, five others with reactive, fupctional or drug-induced hypoglycemia, nor four healthy volunteers showed any changes in circulating glucose or insulin levels while receiving calcium intravenously. Calcium infusion is a safe, rapid and effective provocative test for the diagnosis of insulin-secreting, islet cell tumors of the pancreas.

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.

Letter: Drug-induced hypoglycemia.

Letter: Drug-induced hypoglycemia.

Drug-Induced Hypoglycemia

<h3>To the Editor.—</h3> We wish to report an interesting case of drug-induced hypoglycemia to call attention to the severity and duration from a small dose of chlorpropamide in a healthy young patient. A 17-year-old youth in excellent health, but with a history of occasional marihuana abuse, took 500 mg of chlorpropamide orally three days prior to admission, and another 250 mg one day later. He was found at home unconscious and was hospitalized. Blood glucose level was 34 mg/100 ml, and he awoke after intravenous infusion of 50 ml of 50% glucose. The history was noncontributory for endocrine disease, recent fasting, alcohol intake, or other drug ingestion for two weeks. Additional intravenous infusion of 5% glucose was begun, but ten hours later, he became diaphoretic and incoherent, and thrashed about in bed. The blood glucose level was now 30 mg/100 ml. He became calm and lucid after the administration of

Drug-induced hypoglycemia. A review based on 473 cases.

Both recognition and prevention of drug-induced hypoglycemia require awareness of the clinical conditions favoring its occurrence and the drugs and drug combinations most likely to cause it. Restricted food intake, age, hepatic disease and renal disease are the main predisposing factors, individually and even more so in combination. Everyone in general, and insulin-requiring diabetics in particular, should always eat carbohydrate whenever they drink alcohol. Sulfonylurea hypoglycemia has been reported often in diabetics older than fifty years, with more cases treated with chlorpropamide being reported than cases treated with other sulfonylureas ; it should therefore be used warily in older patients, and only when they are under daily observation by family or friends. In elderly diabetics taking any sulfonylurea agent, warfarin should be used for anticoagulation instead of bishydroxycoumarin, indomethacin for arthritic pain instead of phenylbutazone, and another agent than sulfisoxazole for urinary tract infections. Also in elderly diabetics using sulfonylureas, therapeutic doses of salicylates, monoamine-oxidase inhibitors and probably pro-pranolol should be co-administered with caution, including frequent blood glucose monitoring as long as necessary. Finally, the danger of refractory hypoglycemia in the newborn .proscribes the mother's use of sulfonylureas during the last month of pregnancy. Drug-induced hypoglycemia is now so relatively common that virtually every unconscious patient should be considered hypoglycemie until immediate estimation of the blood sugar level rules the condition in or out. If it is ruled in, the clinician should promptly start 10 per cent glucose by vein and plan to maintain it uninterruptedly for one or more days, with added hydrocortisone and glucagon if necessary, until persistent hyperglycemia guarantees that all drug effects have worn off.

Diabetic Emergencies: Drug-Induced Hypoglycemia

Diabetic Emergencies: Drug-Induced Hypoglycemia