Drugs online research references
Atherosclerosis. 1978 Jul;30(3):165-75.
Effect of metformin on lipid metabolism in the rabbit aortic wall.
Marquie G.
The aim of the present study was to investigate whether metformin was capable of altering aortic lipid metabolism. Pretreatment of rabbits for 8 days with 120 mg/kg per os metformin reduced by 50--70% the incorporation of a 20 muCi tracer doseof [4(-14)C]cholesterol (given orally 24 h before) into various segments of aorta, plasma, liver, intestine and lung, as compared with control animals. However, as intestinal absorption of cholesterol was also diminished in the same proportion, it was then decided to inject the labelled cholesterol directly into the blood. Under these conditions, metformin induced the same reduction in [4(-14)C]cholesterol specific activity in the aorta, but not in other tissues. Three hours after intravenous injection of a 200 muCi tracer dose of [2(-14)C]-acetate, metformin strongly diminished the radioactivity of total lipids of the aorta, both in fed-rabbits and in rabbits on a 24 h fast, independently of the plasma radioactivity level. The inhibition of acetate incorporation into arterial lipids was observed in all lipid fractions (i.e. free and esterified cholesterol, free fatty acids, phospholipids and especially triglycerides) and the effect persisted unaltered over periods of increasing length after the injection of precursor (1/4, 1/2, 1, 3, 5, 8, 12 h). Metformin also significantly inhibited lipid biosynthesis in the liver and intestine. These properties, added to others previously described, can to a large extent explain the preventive effect of metformin on experimental atherosclerosis.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=678317&dopt=Abstract
Br Med J. 1978 Aug 12;2(6135):464-6.
Epidemiology of adverse drug reactions to phenformin and metformin.
Bergman U, Boman G, Wiholm BE.
Adverse drug reactions (ADRs) to phenformin and metformin reported to the Swedish Adverse Drug Reaction Committee during 1965--77 were analysed in relation to sales and prescription data. The biguanides accounted for 0.6% of all reported adverse drug reactions but for 6% of the fatal cases (all phenformin). Sixty-four ADRs to phenformin and eight to metformin were classified as causal relation "probable" or "not excluded." Fifty-one of these reactions (71%) were lactic acidosis, all but one being reactions to phenformin. After 1973 phenformin was prescribed less in Sweden and metformin became predominant. A nationwide prescription survey during 1975--6 disclosed no differences in age and sex between patients receiving phenformin and metformin. The mean daily doses prescribed in 1976 were 74 mg of phenformin and 1.5 g of metformin. The numbers of ADRs to the two drugs reported during 1975--7 were related to use. The relative incidences of ADRs reported for phenformin and metformin did not differ. Significantly more cases of lactic acidosis and deaths were reported for phenformin.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=678924&dopt=Abstract
Klin Wochenschr. 1978 Sep 1;56(17):843-53.
[Lactic acidosis--a possible complication in buformin-treated diabetics (author's transl)]
[Article in German]
Deppermann D, Heidland A, Ritz E, Horl W.
Lactic acidosis is defined as a state of metabolic acidosis (arterial pH below 7.36) due to an increase in the blood concentration of lactate above 2 mEq/l. Lactic acidosis may occur under a variety of conditions; the biguanide-induced lactic acidosis is due to the toxic effects of biguanides (buformin, metformin, phenformin). The clinical picture is characterized by the occurrence of disturbances of consciousness, severe acidosis with Kussmaul's respiration, shock, hypothermia and in about 30% of all cases hypoglycemia. Apart from the general principles of intensive medical care, therapy should comprise correction of the acid-base-disturbances and elimination of the offending biguanide. The efficacy of hemodialysis in the treatment of biguanide-induced lactic acidosis is difficult to evaluate. By a more sensible use of biguanides, lactic acidosis secondary to drug administration should become a rare event.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=713413&dopt=Abstract
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