Severe hypoglycemia in an elderly patient treated with metformin.

UNLABELLED: The following case of severe hypoglycemia was reported during a systematic evaluation of hospital admissions caused by adverse drug reactions (supported by BfArM). HISTORY AND FINDINGS ON ADMISSION: 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. CONCLUSIONS: 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.

Pattern of outpatient drug therapy in diabetics admitted to hospital--preliminary results.

UNLABELLED: The prevalence of outpatient treatment with various drug groups is significantly higher in diabetics than in non-diabetic control patients. In addition to the specific diabetes-related prescriptions, diabetics were more frequently treated with drugs acting on the alimentary tract or used in metabolic disorders (ATC code A), drugs used in disorders of the blood and blood-forming organs (ATC B), cardiovascular system (ATC C), musculo-skeletal system (ATC M) and nervous system (ATC N)-- resulting in markedly higher outpatient costs in this patient group. Objective of this investigation was to analyze the pre-hospital prescription pattern of diabetics and non-diabetic controls at the time of admission to hospital. METHOD: A sample survey of a total of 189 general medical and 68 surgical admissions involving diabetics and 676 and 143 non-diabetic control patients corresponding in age, sex and main diagnosis--were analyzed with regard to selected medical and demographic characteristics and pharmacotherapy. RESULTS AND DISCUSSION: The prevalence of non-diabetic drug treatment in diabetics was highest for ATC C (87.8% and 69.1%), ATC A (40.7% and 27.9%; without A10) and ATC B (39.2% and 29.4%) in internal and surgical admissions, respectively. A substantially higher prevalence was found for ATC groups B and C in diabetics and controls admitted to medical wards than in epidemiological prescription analyses. CONCLUSION: Data indicate that the need for treatment with cardiovascular drugs and drugs used to treat disorders of the blood and blood-forming organs may be associated with a higher risk of hospitalization in general medical wards.

[Serum level-adjusted dosage of once-daily aminoglycoside therapy in critical illness: results of a prospective study]. / Serumspiegelorientierte Dosierung der einmal täglichen Aminoglykosidtherapie beim kritisch Kranken: Ergebnisse einer prospektiven Untersuchung.

OBJECTIVE: In critically ill patients, the adjustment of target peak and trough levels of tobramycin was investigated because aminoglycoside pharmacokinetics can be changed by multiple influences. Sufficient but not too high peak serum concentrations and low trough levels, however, should be achieved to ensure a therapeutic effect and to minimize toxicity. METHODS: 70 critically ill patients of 51 +/- 18 years were monitored daily during their aminoglycoside treatment on the intensive care unit targeting a peak of about 12 micrograms/ml 30 minutes after infusion and a trough level below 1 to 2 micrograms/ml. Dose recommendations were given daily, taking into consideration serum levels, dose predictions (Bayesian method, ABBOTTBASE), creatinine clearance and clinical findings. Creatinine clearance was estimated according to the Cockcroft-Gault-formula as well as directly by the urine collection method. RESULTS: The standardized initial dose of 400 mg tobramycin led to average peak serum levels of 14.2 +/- 3.9 micrograms/ml in the patients with an apparent distribution volume of 0.345 +/- 0.074 L/kg. In 95% of the patients, the initial peak was higher than 8.5 micrograms/ml; levels higher than 20 micrograms/ml were observed in 7%, extremely low concentrations (below 5 micrograms/ml) in 2%. With individually adjusted doses between 160 and 560 mg, a mean peak of 11.5 +/- 2.7 micrograms/ml was measured subsequently. The levels amounted to 96 +/- 23% of the predicted values, deviations greater than 50% occurred in 5%. The target trough level was achieved in 99%, in less than 3% the dosing interval was extended up to 72 hours. A tobramycin clearance below 80 ml/min/1.73 m2 was associated with average 80% and 33% higher creatinine clearance values according to the Cockcroft-method and the direct method, respectively. CONCLUSION: Target peak and trough aminoglycoside levels are adjustable even in critically ill patients. Reduced tobramycin clearance can be associated with normal creatinine clearance. Assuming an exact methodology, a reduced "direct" creatinine clearance, however, indicates a reduced drug clearance.

Epidemiological data on drug use during pregnancy in Thuringia, East Germany, 1993.

An international collaborative WHO-study on drug use in pregnancy of 1987 involving 300 puerperae from Thuringia, East Germany (the former GDR), has partly shown great differences in drug use habits between the countries which had participated on the study. In 1993--after the radical change on the socioeconomic situation in East Germany by the reunification of Germany leading also to changes in health service--an update of the East German data was carried out by repeating the investigation in the same Thuringian region as in 1987. Whereas drug therapy of chronic diseases in pregnancy and drug administration under delivery were widely similar in both investigations, we found a marked increase in drug use in case of illness in the course of pregnancy before admission to hospital for delivery but also in the treatment of nursing women. The differences can be partly put down to socioeconomic development. Because of the continuously enlarging drug market on the one hand and a small data basis on drug risks and side-effects for unborn life on the other hand, a large screening on drug exposition in pregnancy including recording of newborns' data ought to be performed.

Renal excretion and renal tubular transport of p-aminohippurate (PAH) in methimazole treated, hypothyroid rats of different ages.

Thyroid hormone deficiency following treatment with methimazole for 7 days does not reduce PAH secretion in renal tubular cells as expected from data in thyroid hormone treated rats. This treatment with methimazole causes an increase in renal excretion of PAH in rats of various age groups, statistically significant in 5-, 10- and 20-day-old rats. In 20-day-old, methimazole treated rats the increase in renal excretion of PAH is obviously caused by a higher transport rate in renal tubular cells, proved also in 33-day-old rats. An increased filtered fraction of PAH in 5- and 10-day-old rats could be the reason for the rise in renal excretion of PAH after repeated treatment with methimazole. The mechanism of renal effects of methimazole treatment remains unclear.