Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ortho,para,dichlorodiphenyl dichloroethane (o,p'DDD, Mitotane (Roussell)) is used as an adrenolytic drug to reduce adrenocortical mass and circulating cortisol levels in Cushing's syndrome but has the unwanted side-effect of inducing hypercholesterolaemia. This paper examined the mechanism of that effect in 30 patients with Cushing's syndrome treated with o,p'DDD during the past 10 years. o,p'DDD increased serum cholesterol by 68 per cent, mainly by increasing LDL-cholesterol. The latter effect was not due to impaired binding of LDL to its receptor, as shown in vitro using cultured fibroblasts. Increases in plasma mevalonic acid during o,p'DDD administration were suggestive of increased cholesterol synthesis, this effect being reversed by simvastatin. These findings suggest that o,p'DDD causes hypercholesterolaemia by increasing cholesterol synthesis. It is proposed that this effect is due to the drug's known ability to block cytochrome P450-mediated reactions, thus impairing the formation of oxysterols responsible for down-regulating hepatic cholesterol synthesis. Treatment with simvastatin, an inhibitor of cholesterol synthesis, reverses the hyperlipidaemia and enables o,p'DDD therapy to be maintained without increasing cardiovascular risk.
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PMID:Possible mechanism and treatment of o,p'DDD-induced hypercholesterolaemia. 148 Jul 41

Cardiovascular risk factors such as hypertension, hyperlipidemia and glucose intolerance are highly prevalent in Cushing's syndrome. Lipid abnormalities have been reported in 40-70% of patients, including those with 'subclinical' disease. Surgical cure is associated with significant amelioration of lipid profile in the majority of patients. Treatment of persistent hyperlipidemia should be conducted according to the accepted general principles in use for other medical conditions. Nevertheless, patients requiring medical treatment for persistent hypercortisolism present specific challenges, according to the selected therapeutic agent. For example, treatment with the adrenolytic drug o,p'DDD is associated with a prominent increase in cholesterol levels that necessitates intensive use of lipid lowering agents. The use of ketoconazole, a potent inhibitor of cytochrome P450 3A4 (CYP3A4), may significantly increase plasma concentrations of certain statins (such as simvastatin and atorvastatin) that undergo metabolism by the same pathway, thus increasing the risk of complications and side effects. Therefore, preference should be given to HMG-CoA inhibitors that are metabolized by different pathways, such as pravastatin. In summary, hyperlipidemia should be aggressively treated in patients with Cushing's syndrome in view of the increased cardiovascular morbidity and mortality associated with this disorder.
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PMID:Management of dyslipidemia in Cushing's syndrome. 2082 26

The direct oral anticoagulants (DOAC) dabigatran, rivaroxaban, and apixaban are increasingly prescribed in atrial fibrillation (AF) patients, although dosage in elderly patients, safety in chronic kidney disease, food- and drug-interactions, laboratory tests for monitoring, and antidote are not clarified. In a 78-year-old man with an acute stroke, paroxysmal AF and sick-sinus-syndrome were detected as he received a DDD-pacemaker and 5 mg apixaban/bid. He had a history of hypertension, hypothyroidism, diabetes mellitus, hyperlipidemia, sleep apnea, lumbar discopathy, and nephropathy. Renal function deteriorated after 2 months, and apixaban was changed to phenprocoumon. Three months later, he suffered from abdominal pain and hemorrhagic shock due to rupture of an infrarenal aortic aneurysm. After reversal of the anticoagulation with prothrombin-complex concentrate, a stent-graft with exclusion of the aneurysm was implanted. Switching from apixaban to phenprocoumon was probably life-saving. Vitamin-K-antagonists should be preferred to DOAC in patients with AF and vascular disease.
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PMID:A Probable Life-Saving Switch from Apixaban to Phenprocoumon. 2650 41