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ADEs in ambulatory care are common, with many being preventable and many resulting in hospitalization. Quality improvement programs should target errors in prescribing and monitoring, especially for patients using cardiovascular, analgesic, and hypoglycemic agents.

Dose-effect titrated treatment with either metformin or glyburide promotes equal degrees of glycemic control. The former, but not the latter, is able to achieve this control without increasing body weight or hyperinsulinemia. Near-normal glycemia can be obtained by a combination of metformin and sulfonylurea, even in advanced NIDDM.

Food intake exerts a complex influence on the bioavailability of drugs. It may interfere not only with tablet disintegration, drug dissolution and drug transit through the gastrointestinal tract, but may also affect the metabolic transformation of drugs in the gastrointestinal wall and in the liver. Different food components can have different effects, and food may interact in opposite ways, even with drugs that are chemically related. Therefore, the net effect of food on drug bioavailability can be predicted only by direct clinical studies of the drug in question. As judged mainly from single meal, single dose studies, food intake enhances the bioavailability of several different drugs, such as propranolol, metoprolol, hydrallazine, hydrochlorothiazide, canrenone (from spironolactone), nitrofurantoin, erythromycin (stearate), dicoumarol, phenytoin and carbamazepine, but reduces that of drugs such as isoniazid, rifampicin, tetracycline, penicillin and ampicillin, while having no consistent effect on the bioavailability of metronidazole, oxazepam, melperone, propylthiouracil, sulphasomidine and sulphonylureas. For some drugs such as digoxin and paracetamol, the rate but not the extent of absorption is reduced. Food may enhance bioavailability even though, or rather because, the rate of gastric emptying is reduced; this is apparently the case with hydrochlorothiazide and nitrofurantoin. The food induced enhancement of bioavailability of propranolol, metoprolol and hydrallazine is probably due to reduced first pass metabolism of these drugs, while food induced improvement of drug dissolution may explain the enhanced bioavailability of carbamazepine, canrenone, dicoumarol and phenytoin. An increased gastrointestinal pH may be in part the cause of the food induced reduction of the bioavailability of drugs such as isoniazid and tetracycline. In addition to single meal effects, repeated intake of protein-rich meals enhance, while carbohydrate-rich meals reduce, the rate of oxidation of antipyrine and theophylline. Moreover, intake of charcoal broiled meat markedly accelerates the oxidation of phenacetin and variably accelerates elimination of theophylline. Thus, food and its components and contaminants may have both short and long term effects on both the absorptive and biotransformation processes influencing systemic availability of drugs.

In a diabetes detection survey carried out between 1962 and 1965, 2477 (1.1%) of 228,883 subjects had Clinistix-positive glucosuria after a carbohydrate-rich luncheon meal. Of these 2477, 578 displayed impaired tolerance to oral glucose without having manifest diabetes. From this group, 267 men were divided into five groups and subjected to the following treatments and controls: (a) diet regulation and 0.5 g tolbutamide t.i.d. (N = 49), annual oral glucose tolerance test (OGTT); (b) diet regulation and one placebo tablet t.i.d. (N = 48), annual OGTT; (c) diet regulation only (N = 50), annual OGTT; (d) no treatment (N = 61), annual OGTT; and (e) no treatment, OGTT at follow-up (N = 59 at follow-up). In addition, a control group was included comprised of men with normal OGTT (N = 52). At follow-up, 29% of those without diet regulation and medication (group e: N = 59) had developed diabetes. Of those on diet regulation, but without active medication (group b plus group c, N = 98), 13% had diabetes. No individual maintaining tolbutamide and diet regulation (N = 23) had progressed to diabetes. In this group, 80% of those later examined (N = 11) had serum tolbutamide concentrations in the therapeutic range. No individual with initially normal OGTT developed diabetes or impaired OGTT. The findings suggest that normal oral glucose tolerance signifies little risk of progress to impaired glucose tolerance and manifest diabetes, whereas impaired glucose tolerance is associated with a high risk of progression to diabetes. In addition, it seems possible that treatment with diet regulation, in combination with tolbutamide, may prevent or postpone progression from impaired glucose tolerance to manifest diabetes.

The possible influence of cigarette smoking on goiter formation, thyroglobulin (Tg) secretion, and thyroid hormone production was assessed by estimations of the presence of palpable goiter and by RIAs of Tg, T3, rT3, T4, and TSH in sera from 441 women (48-53 yr old), representing a normal population included in a study on the prevalence of thyroid disease. Smoking habits were evaluated by a questionnaire, and the women were then classified as never smokers (n = 192), smokers (n = 169), and exsmokers (n = 80). Smokers were subdivided as moderate (1-19 cigarettes/day) and heavy (greater than or equal to 20 cigarettes/day). Palpable goiter was found in 15% of the smokers, in contrast to only 4% of the exsmokers and 9% of the never smokers. Among smokers, 37% had serum Tg values over 30 micrograms/liter (third quartile), while such values were found in only 16% of the exsmokers and 18% of the never smokers. In addition, smokers were found to have higher serum T3 and lower rT3 concentrations than never smokers; this difference was most pronounced in heavy smokers. Serum T4 was not different, while TSH was insignificantly lower in smokers than in nonsmokers. Exsmokers did not differ significantly from never smokers in any of these parameters. It seems possible that cigarette smoking may have two, calorigenically opposed, effects on thyroid hormone production; it may be goitrogenic (possibly due to inhaled thiocyanate), but it may also enhance the formation of T3 at the expense of rT3 formation.

Objectives — (1) To document types and number of drug‐related problems identified by community pharmacy personnel in Sweden; (2) to determine relationships among the types and number of problems identified and the gender, age and number of prescribed drugs in patients; and (3) to document the interventions made by pharmacy personnel with patients and prescribers. Method — Random samples of pharmacists, prescriptionists and pharmacy technicians were drawn nationwide in Sweden; 144 (63 per cent) of the employees fulfilling the inclusion criteria agreed to take part. The participants documented drug‐related problems, interventions and patient variables on a data collection form, and tallied the number of patients they served on another form. Setting — One hundred and sixteen community pharmacies and 12 outpatient hospital pharmacies. Key findings — One problem or more was identified among 2.5 per cent of the patients. The median number of problems identified per 100 patients was greater for pharmacists (6.1) than for prescriptionists (2.6) and pharmacy technicians (1.1). About one in three problems was presented to the participants by their patients, while two thirds were detected by the pharmacy staff. One in four problems was related to dosage, and one in five to uncertainty about the aim or function of the medication. Problems were over‐represented among children and the younger middle‐aged and under‐represented in the elderly. Patient medication counselling was the most common type of intervention. When contacted, the physician nearly always approved the recommendation made by the pharmacy staff. Conclusion — The results led to suggestions as to how pharmacy practitioners can augment pharmaceutical care through drug‐related problem detection.

Both sulphonylureas (SU) and metformin (MET) reduce hyperglycaemia in patients with Type II (non-insulin-dependent) diabetes mellitus, but they do so by entirely different mechanisms. Therefore, SU and MET can be combined, and a few controlled studies have shown pronounced reductions in hyperglycaemia following treatment with this combination [1±3]. As SU and MET also have beneficial long-term effects on diabetic microvascular disease [4,5] and MET even on macrovascular disease [5], it would seem logical to presume that the combination of SU and MET would be highly beneficial for ischaemic heart disease (IHD) and stroke in patients with Type II diabetes. A UKPDS substudy instead reported a higher risk of diabetes-related death with this type of combination therapy compared with SU therapy alone [5]. Therefore, we decided to analyse cause- Diabetologia (2000) 43: 558±560 Articles Short communicationIncreased mortality in Type II diabetic patients using sulphonylurea and metformin in combination: a population-based observational study