Drugs online research references
Diabete Metab. 1979 Jun;5(2):103-12.
[Light and electron microscopic study of hepatic lesions in the course of hyperlactatemia in diabetic patients (author's transl)]
[Article in French]
Larcan A, Lambert H, Laprevote-Heully MC, Delorme N.
Histopathological study of the liver has been undertaken on twenty-one diabetics with hyperlactatemia exceeding 5 mEq/1 of whom seven were treated with phenformin, six with metformin and eight not biguanide-treated. Hyperlactatemia occurred during the course or during resolution of severe ketoacidosis or of hyperosmolar coma. Hepatic lesions were invariably present. By light microscopy, massive steatosis, steatonecrosis or necrosis of variable extent were observed. Ultrastructural study showed constant mitochondrial abnormalities. These results support the hypothesis of a major role for mitochondrial changes in hepatic cells in provoking pathological hyperlactatemia. In diabetic patients, these mitochondrial lesions could be induced either by an anoxic process resulting from a variety of metabolic insults or by some as yet undefined toxic action of biguanides or by the combination of both of these factors.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=113262&dopt=Abstract
ucalgary.ca
K(+) currents were measured using a whole cell voltage-clamp method in enzymatically isolated rat ventricular myocytes obtained from two hyperinsulinemic, insulin-resistant models. Fructose-fed rats as well as genetically obese rats, both of which are resistant to the metabolic effects of insulin, were used. The normal augmentation of a calcium-independent sustained K(+) current was reduced or abolished in insulin-resistant states. This resistance can be reversed by the insulin-sensitizing drug metformin. Vanadyl sulfate (3-4 wk treatment or after 5-6 h in vitro) enhanced the sustained K(+) current. The in vitro effect of vanadyl was blocked by cycloheximide. Insulin resistance of the K(+) current was not reversed by vanadyl sulfate. The results show that insulin resistance is expressed in terms of insulin actions on ion channels, in addition to its actions on metabolism. This resistance can be reversed by the insulin-sensitizing drug metformin. Vanadate compounds, which mimic the effects of insulin on metabolism, also mimic the augmenting effects of insulin on a cardiac K(+) current in a manner suggesting synthesis of new channels.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10924063&dopt=Abstract
Acta Med Scand Suppl. 1984;683:107-17.
Drug utilization and morbidity statistics for the evaluation of drug safety in Sweden.
Wiholm BE, Westerholm B.
For a continuous monitoring and evaluation of drug safety problems in Sweden, the Department of Drugs of the National Board of Health and Welfare has access to a number of computerised patient-, drug-, and disease-oriented registers. The usefulness and limitations of these registers are presented by examples. A recent increase in asthma deaths is presently being analysed by comparing information from death certificates and case records with drug sales and prescription data. A recent analysis of the cancer register showed no increased risk of malignant thyroid tumors after diagnostic or therapeutic doses of I 131. Similarly no increased risk of malformations after occupational exposure to hexachlorophene could be detected by analysing the malformation and medical birth-record registers in relation to hospital hexachlorophene use. The register of patient discharge diagnoses has been repeatedly used to analyse the incidence and pattern of drug induced blood dyscrasias and thromboembolism associated with oral contraceptives (OC). These analyses have resulted i.a. in the withdrawal of dipyrone and tenalidine and a decrease of the estrogen-content of OCs. At the same time about 1/3 of these serious adverse drug reactions (ADR) was found to have been reported to the ADR-register. By combining sales and prescription data with ADR-reports the risk of inducing lactic acidosis was found to be significantly higher for phenformin than for metformin. Also the incidence of tardive dyskinesia from longterm use of metoclopramide was found to be much higher than hitherto recognized. By use of these registers it is possible to obtain valuable information about the safety of drugs. The raw data must, however, be interpreted with care and often be supplemented with in depth studies of the various problems.
PIP: For a continuous monitoring and evaluation of drug safety problems in Sweden, the Department of Drugs of the National Board of Health and Welfare has access to a number of computerized patient, drug, and disease-oriented registers. The usefulness and limitations of these registers are presented by examples. A recent increase in asthma deaths is presently being analyzed by comparing information from death certificates and case records with drug sales and prescription data. A recent analysis of the cancer register showed no increased risk of malignant thyroid tumors after diagnostic or therapeutic doses of I131. Similarly no increased risk of malformations after occupational exposure to hexachlorophene could be detected by analyzing the malformation and medical birth record registers in relation to hospital hexachlorophene use. The register of patient discharge diagnoses has been repeatedly used to analyze the incidence and pattern of drug-induced blood dyscrasias and thromboembolism associated with oral contraceptives (OC). These analyses have resulted in the withdrawal of dipyrone and tenalidine and a decrease of the estrogen content of OCs. At the same time, about 1/3 of these serious adverse drug reactions (ADRs) had been reported to the ADR register. By combining sales and prescription data with ADR reports, the risk of inducing lactic acidosis was significantly higher for phenformin than for metformin. Also, the incidence of tardive cyskinesia from longterm use of metoclopramide was much higher than recognized previously. With these registers it is opossible to obtain valuable information about drug safety. The raw data must, however, be interpreted with care and often be supplemented with in-depth studies of the various problems.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6430038&dopt=Abstract
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