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At least 91 records · Page 5Linked to original sources
PubMed2002

Experimental approaches to study PPAR gamma agonists as antidiabetic drugs.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors that are related to retinoid, steroid and thyroid hormone receptors. Since PPARs appear to be closely involved in the regulation of dietary fat storage and catabolism, they have been established as an important target for the treatment of type 2 diabetes and other disorders associated with the high intake of dietary fat. Thiazolidinediones (TZDs) were the first class of compounds to be identified as PPAR gamma-ligands, constituting a new class of antidiabetic drugs that have recently been introduced as therapeutic agents for the treatment of type 2 diabetes mellitus by acting as insulin sensitizers. These compounds improve insulin resistance by increasing cell sensitivity to insulin. In fact, PPAR gamma agonists increase peripheral insulin sensitivity by increasing the transcription of genes, which, in turn, increase glucose uptake, also improving insulin-stimulated glucose disposal in muscle. PPAR gamma agonists increase insulin signaling, reduce circulating levels of free fatty acids and stimulate adipocyte differentiation, thus favoring the formation of smaller, more insulin-sensitive adipocytes. TZDs have been proven effective in different experimental models to evaluate their effectiveness as an antidiabetic agent, and the involvement of PPAR gamma in the pharmacological effects of these compounds has been supported by studies showing an excellent correlation between the hypoglycemic action of these drugs and their affinity for PPAR gamma. Despite this evidence, the site of action and the molecular mechanism of TZDs remain unclear. The aim of the present article was to review and discuss the most relevant pharmacological studies performed in the search for establishing the mechanism of action of antidiabetic TZDs and related compounds acting as PPAR gamma agonists, as well as to summarize those representative experimental approaches currently used to evaluate PPAR gamma agonists as therapeutic agents for the treatment of insulin-resistant type 2 diabetes mellitus.

Animals↗
PubMed2005

Antinociceptive, antiinflammatory and antidiabetic effects of Leonotis leonurus (L.) R. BR. [Lamiaceae] leaf aqueous extract in mice and rats.

The present study was undertaken to investigate the antinociceptive, antiinflammatory, and antidiabetic properties of the aqueous leaf extract of Leonotis leonurus (L.) R. BR. (Lamiaceae) in mice and rats, to scientifically appraise some of the plant's ethnomedical uses, and its safety and efficacy. The leaf powder of the plant was Soxhlet extracted with distilled water and used. The antinociceptive effect of the plant's extract was evaluated by the "hot-plate" and "acetic acid" test models of pain in mice, while the antiinflammatory and antidiabetic effects of the leaf extract were investigated in rats, using fresh egg albumin-induced paw edema, and streptozotocin (STZ)-induced diabetes mellitus, respectively. Morphine (MPN, 10 mg/kg i.p.), diclofenac (DIC, 100 mg/kg i.p.), and chlorpropamide (250 mg/kg p.o.) were used, respectively, as reference analgesic, antiinflammatory, and hypoglycemic agents for comparison. L. leonurus leaf aqueous extract (LLE, 50-800 mg/kg i.p.) produced dose-dependent and significant (p < 0.05-0.001) antinociceptive effects against thermally and chemically induced nociceptive pain stimuli in mice. LLE (50-800 mg/kg i.p.) also significantly (p < 0.05-0.001) inhibited fresh egg albumin-induced paw edema, and caused significant (p < 0.05-0.001) hypoglycemic effects in rats. It is suggested that the analgesic effects of LLE (50-800 mg/kg i.p.) may be peripherally and centrally mediated. The different flavonoids, diterpenoids, polyphenolics, and other chemical constituents of the plant may be involved in the observed antinociceptive, antiinflammatory, and antidiabetic effects of the plant's extract. However, the results of this experimental animal study suggest that the aqueous leaf extract of L. leonurus possesses antinociceptive, antiinflammatory, and hypoglycemic properties, and thus lend pharmacological credence to the suggested folkloric uses of the herb in the management and/or control of painful, arthritic, and other inflammatory conditions, as well as for adult-onset, type-2 diabetes mellitus in some communities of South Africa.

Acetic Acid↗
PubMed1998

Effects of antineoplastics, antibiotics and antidiabetics on acetaldehyde metabolism after alcohol ingestion.

The main purpose of this study was to evaluate the inhibitory effects of 5-fluorouracil antineoplastics, cephem antibiotics containing the methyltetrazolylthiol (MTT) group and antidiabetics on aldehyde dehydrogenase (ALDH) activity in vivo and in vitro. In in vivo experiments, rats were given a 100 mg/kg dose of drugs (10 mg/kg for glibenclamide) orally or intraperitoneally. When each drug was administered singly immediately after an oral administration of 1.5 g/kg ethanol, only carmofur, an antineoplastic, produced marked increases in blood acetaldehyde concentrations. This action was also noted when ethanol was ingested 15 h after administration. The remaining drugs did not increase blood acetaldehyde concentrations. When rats were treated with carmofur at 12 h intervals for 3 consecutive days and were given 1.5 g/kg ethanol after the final treatment, blood acetaldehyde concentrations were elevated more significantly than with a single administration of carmofur. Furthermore, daily administration of cephem antibiotics containing the MTT group, latamoxef, cefamandole, cefoperazone and cefbuperazone, significantly increased blood acetaldehyde concentrations. Daily administration of sulfonylurea antidiabetics, chlorpropamide and acetohexamide, slightly increased blood acetaldehyde concentrations. Drugs causing increases in blood acetaldehyde concentrations when administration was combined with ethanol ingestion also inhibited ALDH activity in vitro. The results of the in vitro experiments roughly correlated with those of the in vivo experiments. The inhibitory effects of drugs on ALDH activity were in the following order: carmofur >> cephem antibiotics containing the MTT group > sulfonylurea antidiabetics.

Acetaldehyde↗
PubMed2005

Effect of genetic polymorphisms in cytochrome p450 (CYP) 2C9 and CYP2C8 on the pharmacokinetics of oral antidiabetic drugs: clinical relevance.

Type 2 diabetes mellitus affects up to 8% of the adult population in Western countries. Treatment of this disease with oral antidiabetic drugs is characterised by considerable interindividual variability in pharmacokinetics, clinical efficacy and adverse effects. Genetic factors are known to contribute to individual differences in bioavailability, drug transport, metabolism and drug action. Only scarce data exist on the clinical implications of this genetic variability on adverse drug effects or clinical outcomes in patients taking oral antidiabetics. The polymorphic enzyme cytochrome P450 (CYP) 2C9 is the main enzyme catalysing the biotransformation of sulphonylureas. Total oral clearance of all studied sulphonylureas (tolbutamide, glibenclamide [glyburide], glimepiride, glipizide) was only about 20% in persons with the CYP2C9*3/*3 genotype compared with carriers of the wild-type genotype CYP2C9*1/*1, and clearance in the heterozygous carriers was between 50% and 80% of that of the wild-type genotypes. For reasons not completely known, the resulting differences in drug effects were much less pronounced. Nevertheless, CYP2C9 genotype-based dose adjustments may reduce the incidence of adverse effects. The magnitude of how doses might be adjusted can be derived from pharmacokinetic studies. The meglitinide-class drug nateglinide is metabolised by CYP2C9. According to the pharmacokinetic data, moderate dose adjustments based on CYP2C9 genotypes may help in reducing interindividual variability in the antihyperglycaemic effects of nateglinide. Repaglinide is metabolised by CYP2C8 and, according to clinical studies, CYP2C8*3 carriers had higher clearance than carriers of the wild-type genotypes; however, this was not consistent with in vitro data and therefore further studies are needed. CYP2C8*3 is closely linked with CYP2C9*2. CYP2C8 and CYP3A4 are the main enzymes catalysing biotransformation of the thiazolidinediones troglitazone and pioglitazone, whereas rosiglitazone is metabolised by CYP2C9 and CYP2C8. The biguanide metformin is not significantly metabolised but polymorphisms in the organic cation transporter (OCT) 1 and OCT2 may determine its pharmacokinetic variability. In conclusion, pharmacogenetic variability plays an important role in the pharmacokinetics of oral antidiabetic drugs; however, to date, the impact of this variability on clinical outcomes in patients is mostly unknown and prospective studies on the medical benefit of CYP genotyping are required.

Administration, Oral↗
PubMed2002

New trends in the development of oral antidiabetic drugs.

A large number of oral antidiabetic agents are available today. This article provides a short review of the pharmacology and some clinical aspects of various oral antidiabetic drugs. It focuses mainly on the newest developing drugs (therapy of the near future) and on the most commonly used older groups for the common approach of every-day practice (sulphonylureas). The primary goal of this review is to compare the electrophysiological effects of glibenclamide in isolated normal and streptozotocin induced diabetic rats and alloxan induced rabbits ventricular preparations, while on the other hand to differentiate the hypoglycaemic sulphonylureas (0.1-1000 mmol/kg) according to their cardiovascular activity in healthy and diabetic animals. In vitro (1-100 micromol/l) as well as chronically treated (5 mg/kg for 10 weeks) glibenclamide prolonged the action potential duration in normal but failed to affect it in diabetic ventricular preparations. Our results suggest that the sensitivity to glibenclamide of K(ATP) channels in diabetic ventricular fibers is drastically decreased. The effects of different sulphonylureas (tolbutamide, glibenclamide, gliclazide, glimepiride) on ventricular ectopic beats as well as the duration of ventricular fibrillation induced by 10 min ischemia/50 min reperfusion in healthy and diabetic rats were compared. Tolbutamide and gliclazide dose-dependently enhanced both parameters both in healthy and diabetic groups. Glibenclamide in healthy rats increased, while in diabetic rats it decreased the arrhythmogenicity. Glimepiride depressed the arrhythmogenicity in both healthy and diabetic animals. Glimepiride proved to dose-dependently enhance the myocardial tissue flow in dog in contrast to glibenclamide. These results confirm that glimepiride has less cardiovascular actions than other sulphonylureas. From the newest oral antidiabetics this review tries to emphasize the most important basic pharmacological properties, mechanism of action, therapeutic use.

Administration, Oral↗
PubMed2006

Antidiabetic agents from medicinal plants.

Currently available therapeutic options for non-insulin-dependent diabetes mellitus, such as dietary modification, oral hypoglycemics, and insulin, have limitations of their own. Many natural products and herbal medicines have been recommended for the treatment of diabetes. The present paper reviews medicinal plants that have shown experimental or clinical antidiabetic activity and that have been used in traditional systems of medicine; the review also covers natural products (active natural components and crude extracts) isolated from the medicinal plants and reported during 2001 to 2005. Many kinds of natural products, such as terpenoids, alkaloids, flavonoids, phenolics, and some others, have shown antidiabetic potential. Particularly, schulzeines A, B, and C, radicamines A and B, 2,5-imino-1,2,5-trideoxy-L-glucitol, beta-homofuconojirimycin, myrciacitrin IV, dehydrotrametenolic acid, corosolic acid (Glucosol), 4-(alpha-rhamnopyranosyl)ellagic acid, and 1,2,3,4,6-pentagalloylglucose have shown significant antidiabetic activities. Among active medicinal herbs, Momordica charantia L. (Cucurbitaceae), Pterocarpus marsupium Roxb. (Leguminoceae), and Trigonella foenum graecum L. (Leguminosae) have been reported as beneficial for treatment of type 2 diabetes.

Alkaloids↗
PubMed2000

A new thiazolidinedione, NC-2100, which is a weak PPAR-gamma activator, exhibits potent antidiabetic effects and induces uncoupling protein 1 in white adipose tissue of KKAy obese mice.

Thiazolidinediones (TZDs) reduce insulin resistance in type 2 diabetes by increasing peripheral uptake of glucose, and they bind to and activate the transcriptional factor peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Studies have suggested that TZD-induced activation of PPAR-gamma correlates with antidiabetic action, but the mechanism by which the activated PPAR-gamma is involved in reducing insulin resistance is not known. To examine whether activation of PPAR-gamma directly correlates with antidiabetic activities, we compared the effects of 4 TZDs (troglitazone, pioglitazone, BRL-49653, and a new derivative, NC-2100) on the activation of PPAR-gamma in a reporter assay, transcription of the target genes, adipogenesis, plasma glucose and triglyceride levels, and body weight using obese KKAy mice. There were 10- to 30-fold higher concentrations of NC-2100 required for maximal activation of PPAR-gamma in a reporter assay system, and only high concentrations of NC-2100 weakly induced transcription of the PPAR-gamma but not PPAR-alpha target genes in a whole mouse and adipogenesis of cultured 3T3L1 cells, which indicates that NC-2100 is a weak PPAR-gamma activator. However, low concentrations of NC-2100 efficiently lowered plasma glucose levels in KKAy obese mice. These results strongly suggest that TZD-induced activation of PPAR-gamma does not directly correlate with antidiabetic (glucose-lowering) action. Furthermore, NC-2100 caused the smallest body weight increase of the 4 TZDs, which may be partly explained by the finding that NC-2100 efficiently induces uncoupling protein (UCP)-2 mRNA and significantly induces UCP1 mRNA in white adipose tissue (WAT). NC-2100 induced UCP1 efficiently in mesenteric WAT and less efficiently in subcutaneous WAT, although pioglitazone and troglitazone also slightly induced UCP1 only in mesenteric WAT. These characteristics of NC-2100 should be beneficial for humans with limited amounts of brown adipose tissue.

Adipose Tissue↗
PubMed1986

Studies of drug-treated diabetes in the county of Jämtland, Sweden, based on prescription of insulin and oral antidiabetic drugs.

Epidemiological data on drug-treated diabetes mellitus was obtained by analyzing prescriptions of insulin and oral antidiabetics in the county of Jämtland Sweden. During a 12-year period, from 1971 to 1982, the prevalence of diabetes increased from 1.5% to 2.2%, while there was no significant change in the annual incidence of around 2.7/1000 inhabitants. Women displayed a considerable higher prevalence and incidence than men in the over 70 age-group, while in the 50 - 69 age-group there was a male dominance. A significant change in the prescription pattern with an increased use of insulin and decreased use of oral antidiabetics was observed during the period. More patients were started on oral antidiabetics during the first part of the year than during the latter.

Adolescent↗
PubMed2001

[Thiazolidinediones--a new class of oral antidiabetic drugs].

The discovery of a new class of oral antidiabetic drugs was stimulated by difficulties with the treatment currently available for patients with type 2 diabetes mellitus. Thiazolidinediones can lower blood glucose values due to their special insulin-sensitiser effect. In this way, these drugs seem to be very effective in the treatment of type 2 diabetic patients with characteristics of metabolic syndrome. The intracellular action caused by thiazolidinediones differs markedly from that of other oral antidiabetic drugs available. Apart from antihyperglycaemic effect, thiazolidinediones have further beneficial effects in experimental diabetes which require corroboration by clinical studies. Troglitazone was the first drug which reached the market. Unfortunately, this drug was withdrawn soon due to its hepatotoxicity. Rosiglitazone proved to be much safer in clinical studies. Pioglitazone is being tested nowadays in clinical studies. Thiazolidinediones have been already listed among oral antidiabetic drugs in international therapeutical guidelines. Nevertheless, further clinical studies and experiences are needed to determine the final exact indication of thiazolidinediones for the treatment of type 2 diabetic patients.

Animals↗
PubMed2001

Determination of antidiabetic activity in Allium cepa (onion) tissue cultures.

Seedling, seedling parts and callus cultures of onion were tested for their antidiabetic activity by feeding the tissue-extracts to diabetic rats. The results indicated much higher antidiabetic activity in callus cultures as compared to natural bulbs of onion. These results may be of pharmaceutical significance since the callus can be used as an alternative source for the isolation of antidiabetic compounds.

Animals↗
PubMed2004

[Antidiabetic activity of the leaves of Vemonia colorata (Wilid.) Drake (Composees) in alloxan-induced diabetic rats].

Vemonia colorata is distributed through Africa (Benin, Cameroon, Senegal, Togo etc...). Its leaves are commonly used by african tradipractitioners for treating diabetes. However, the antidiabetic activity of the leaves of V. colorata had never been investigated in experimental conditions. The present study aimed to test the aqueous extract of the leaves of V. colorata for its effects in normoglycaemic and alloxan-induced diabetic rats in comparison to glibenclamide antidiabetic activity. Such glibenclamide, the aqueous extract of V. colorata (300 mg/kg, per os) induced a significant hypoglycaemic effect in normoglycaemic rats. The blood glucose varied from 0.77 +/- 0.01 to 0.58 +/- 0.01 g/l (p < 0.05, n = 5). It also reduced significantly the fasting glucose level of the hyperglycaemic rats induced with oral administration of glucose (4 g/kg). In alloxan-induced diabetic rats, glibenclamide (0.2 mg/kg, per os) lowered significantly the blood glucose from 2.40 +/- 0.30 to 0.70 +/- 0.40 g/l (p < 0.05, n = 5). As well as glibenclamide, the aqueous extract of V. colorata (300 mg/kg, per os) decreased the blood glucose in alloxanic rats from 2.80 +/- 0.10 to 1.00 +/- 0.20 g/l (p < 0.05, n = 5). The aqueous extract of the leaves of V. colorata possesses both hypoglycaemic and antidiabetic effect in normoglycaemic and alloxan-induced diabetic rats. This may indicate the ethnopharmacological basis of the use of V. colorata leaves in traditional medicine for treating diabetes.

Administration, Oral↗
PubMed2005

[Practice of antidiabetic therapy in Hungary].

Type 2 diabetes is one of the biggest public health problems of our age. In the present study the authors analyse the development of the therapy of type 2 diabetic patients. National antidiabetic consumption data and data of National Health Insurance Fund Administration (OEP) were used. From OEP database definite method were used to choose 1002 type 2 diabetic patients. The Hungarian therapeutic practice develops according to guidelines of multi centered studies, and the consumption of antidiabetics dynamically increases. Increasing the number of patients who get insulin therapy and among patients who get oral antidiabetics more of them get insulin resistance decreasing therapy. However the out-of-date drugs (non-micronized glibenclamide, buformin) are still in daily therapy. The authors revealed the ratio of diet and drug (monotherapy, combination therapy) therapy, the higher use of Sulfanylurea monotherapy than recommended and the use of unreasonable combinations.

Administration, Oral↗
PubMed1977

[The oral antidiabetics (author's transl)].

Oral antidiabetics are given for preference to adult diabetics who do not need insulin. Biguanides are particularly indicated for adipose diabetics, sulphonamides for those of normal weight. Phenformin must not be used in the presence of renal insufficiency and severe liver diseases because of the high risk of lactacidosis. Oral antidiabetics should not to be given during pregnancy. With oral treatment of diabetics under the age of 30, proteinuria, peripheral vascular diseases and disturbances of fat metabolism occure more frequently while retinopathies, coronary diseases, peripheral neuropathies or infections of the urinary tract cannot be influenced orally, nor by insulin nor by a combination of the two. The i. v. lipid tolerance test is always pathological even in apparently well-adjusted orally treated diabetics. On the other hand it is normal even in less well adjusted insulin therapy. More epidemiological investigations should be carried out in order to be able to assess clearly the longterm effects of oral antidiabetics.

Administration, Oral↗
PubMed1984

Patterns in drug utilization--national and international aspects: antidiabetic drugs.

Data on the prevalence of diabetes in the Czech socialist republic and on the age and sex structure of the diabetic population are presented in this paper as well as the distribution of patients according to type of therapy. The time period studied was 1972 through 1980. The following factors were supposed to affect the level of antidiabetic drug consumption in Czechoslovakia: prevalence of diabetes; organisation of health care; demographic indices and therapeutic traditions. Differences in age and sex structure of the population are probably a major reason for the observed differences in antidiabetic drug consumption between the Czech and the Slovak socialist republics. A good reciprocity was found between the sale of antidiabetic drugs measured as number of defined daily doses (DDD) per 1 000 inhabitants per day and the prevalence of diabetics treated with the corresponding drugs.

Adolescent↗
PubMedDate not supplied

The incidence of congestive heart failure associated with antidiabetic therapies.

BACKGROUND: Increased risk for CHF in persons with type 2 diabetes is well established. Our objectives were to estimate the CHF risk associated with specific therapies for diabetes and to determine the differences in incidence rates of CHF associated with adding various antidiabetic agents. METHODS: Subjects were members of the Kaiser Permanente Northwest (KPNW) diabetes registry as of 1 January 1998, with no prior history of CHF (n = 8063). We identified their therapy as of that date and then defined the start of the subject study period as the date when their drug regimen changed, either by switching to or by adding another antidiabetic drug. We defined the new therapy as the index therapy and the date of initiating the new therapy as the index date. Follow-up on the patients was done until the index therapy was discontinued or changed, or until 31 December 2002, whichever came earlier. We calculated the incidence rate of CHF in patients on various therapeutic regimens adjusting for age, gender, diabetes duration, existing ischemic heart disease, hypertension, renal insufficiency and glycemic control (HbA(1c)). RESULTS: CHF incidence rates were highest in index therapy categories that included insulin and lowest in regimens that included metformin. When insulin was added to an initial therapy, CHF incidence was increased 2.33 times (p < 0.0001) and 2.66 times (p < 0.0001) compared to the addition of sulphonylurea or metformin respectively. CONCLUSIONS: Our findings support the theory that elevated serum insulin levels promote the development of cardiac disease. Consistent with the UKPDS, metformin may offer some protection from incident CHF relative to sulphonylurea or insulin.

Diabetes Mellitus, Type 1↗
PubMed2003

Antidiabetic herbal drugs officially approved in China.

Over the centuries, Chinese herbal drugs have served as a major source of medicines for the prevention and treatment of diseases including diabetes mellitus (known as 'Xiao-ke'). It is estimated that more than 200 species of plants exhibit hypoglycaemic properties, including many common plants, such as pumpkin, wheat, celery, wax guard, lotus root and bitter melon. To date, hundreds of herbs and traditional Chinese medicine formulas have been reported to have been used for the treatment of diabetes mellitus. This paper provides a brief review of the antidiabetic drugs of plant origin that have been approved by the Chinese health regulatory agency for commercial use in China. It was believed, through pharmacological studies, that medicinal herbs were meticulously organized in these antidiabetic drug formulas such that polysaccharide containing herbs restore the functions of pancreatic tissues and cause an increase in insulin output by the functional beta cells, while other ingredients enhance the microcirculation, increase the availability of insulin and facilitate the metabolism in insulin-dependent processes. Pharmacological and clinical evaluations indicated that these drugs had a mild, but significant, blood glucose lowering effect and that the long-term use of these agents may be advantageous over chemical drugs in alleviating some of the chronic diseases and complications caused by diabetes. Additionally, the use of these natural agents in conjunction with conventional drug treatments, such as a chemical agent or insulin, permits the use of lower doses of the drug and/or decreased frequency of administration which decreases the side effects most commonly observed.

Clinical Trials as Topic↗
PubMed2005

Free radical scavenging, enzyme inhibitory constituents from antidiabetic Ayurvedic medicinal plant Hydnocarpus wightiana Blume.

Hydnocarpus wightiana is advocated in traditional Indian medicine to possess strong antidiabetic activity. In the course of identifying bioactive fractions from Indian medicinal plants we observed that acetone extract of the seed hulls of H. wightiana possess strong free radicals (DPPH and ABTS) scavenging, alpha-glucosidase and moderate N-acetyl-beta-D-glucosaminidase inhibitory activities. Further fractionation of the extract led to the isolation of hydnocarpin, luteolin and isohydnocarpin in substantial yields. All the compounds showed strong ABTS scavenging property. However, only luteolin could display strong DPPH scavenging activity. Furthermore, all the three compounds also showed varying degrees of alpha-glucosidase and N-acetyl-beta-D-glucosaminidase inhibitory activity, luteolin being the superior. The kinetics of alpha-glucosidase inhibition by these compounds showed that acetone extract inhibits the enzyme in competitive manner however, luteolin and isohydnocarpin showed mixed-type inhibition. This is the first report assigning hydnocarpin and isohydnocarpin free radical scavenging, alpha-glucosidase and N-acetyl-beta-D-glucosaminidase inhibitory properties and luteolin as N-acetyl-beta-D-glucosaminidase inhibitor. This study suggests that presence of amphiphilic antioxidant molecules along with enzyme inhibitory activities in the acetone extract of H. wightiana seed hulls may be responsible for the antidiabetic properties as advocated in traditional medicine.

Biphenyl Compounds↗
PubMed1985

Validation of observed differences in the utilization of antihypertensive and antidiabetic drugs in Northern Ireland, Norway and Sweden.

The amount of antihypertensive and antidiabetic drugs based of defined daily doses per 1000 inhabitants per day varies two to three fold between Northern Ireland, Norway, and Sweden. We explored whether variations based on the universally applied defined daily doses might be accounted for by national differences in the actual average prescribed daily doses. Use of prescribed daily doses for antihypertensive drugs resulted in Northern Irish and Norwegian consumption figures which were respectively 40 and 21% lower than the Swedish one, compared to 38 and 25% when defined daily doses were used. The effect of population age-sex differences on the gross defined daily doses per 1000 inhabitants per day figures was determined by applying the Northern Irish or Norwegian age-sex group proportions to Swedish age-sex specific sales data. Taking population differences into account would have resulted in antihypertensive drug use being 21 rather than 38% less in Northern Ireland and 18 rather than 25% less in Norway. Also adjustment for prescribed daily doses left an unexplained difference of 23% between Sweden and Northern Ireland and 14% between Sweden and Norway. For oral antidiabetics use of prescribed daily doses resulted in a Northern Irish - Swedish difference of 62% compared to 67% when defined daily doses were used. Simultaneous adjustment for population differences and prescribed to defined daily dose variations left a 52% difference.

Adolescent↗