Simvastatin syndrome

These compounds are structural analogs of HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A, Figure 35-3). Lovastatin, atorvastatin, fluvastatin, pravastatin, simvastatin, and rosuvastatin belong to this class. They are most effective in reducing LDL. Other effects include decreased oxidative stress and vascular inflammation with increased stability of atherosclerotic lesions. It has become standard practice to initiate reductase inhibitor therapy immediately after acute coronary syndromes, regardless of lipid levels. 

Atorvastatin, simvastatin, rosuvastatin Inhibit HMG-CoA reductase Reduce cholesterol synthesis and up-regulate low-density lipoprotein (LDL) receptors on hepatocytes modest reduction in triglycerides Atherosclerotic vascular disease (primary and secondary prevention) t acute coronary syndromes Oral duration 12-24 h Toxicity Myopathy, hepatic dysfunction Interactions CYP-dependent metabolism (3A4, 2C9) interacts with CYP inhibitors... 

Cholestatic hepatitis developed in a 71-year-old man with nephrotic syndrome (2). Hepatic function was normal after several months of fluvastatin 20 mg/day. Some weeks after the dose was increased to 40 mg/day, his gamma-glutamyl transpeptidase activity rose from normal to 1818 IU/1, with negative serology for viruses. After normalization, re-introduction of fluvastatin 20 mg/day was not tolerated, but he did tolerate simvastatin 20 mg/day. 

A 58-year-old man developed a disorder resembling Guillain-Barre syndrome at the start of simvastatin therapy (12). He had had a similar but milder episode after taking pravastatin 6 months before. 

Lupus-like syndrome has been associated with simvastatin, with antibodies to double-stranded DNA in the serum (34). 

In a patient with glucocorticoid-resistant nephrotic syndrome taking simvastatin and ciclosporin, there was an increase in lactic dehydrogenase activity, suggesting tissue injury, in the absence of an increase in creatine kinase (42). 

Ogawa D, Maruyama K, Miyatake N, Kashihara N, Makino H. Concomitant use of simvastatin and cyclosporin A increases LDH in nephrotic syndrome. Nephron 1998 80(3) 351-2. 

A 38-year-old man with major depressive disorder and psychotic features developed rabbit syndrome after taking risperidone 4 mg/day and paroxetine 40 mg/ day for 4 months he was also taking simvastatin 10 mg/day, thiamine 100 mg/day, and folic acid 1 mg/ day (104). 

In hepatorenal syndrome (HRS), which is an acute episode, the clearance of renally excreted drugs and metabolites (pravastatin, simvastatin, rosu-vastatin, acipimox, fibrates) may be reduced. During an episode of HRS, anti-hyperlipidaemic medication should be withheld. 

St. John s wort Cyclosporine Digoxin Indinavir, neverapine MAO inhibitors Oral contraceptives Simvastatin SSRIs Warfarin Decreased levels and decreased effect Decreased levels and decreased effect Decreased levels and decreased effect Increased risk of MAO toxicity Decreased levels and decreased effect Decreased levels and decreased effect Increased risk of serotonin syndrome Decreased levels and decreased effect... 

Vittone F, Chait A, Morse JS, Fish B, Brown BG, Zhao XQ (2007) Niacin plus simvastatin reduces coronary stenosis progression among patients with metabolic syndrome despite a modest increase in insulin resistance a subgroup analysis of the HDL-Atherosclerosis Treatment Study (HATS). J Clin Lipidol 1 203-210... 

Acebutolol Alpha-methyl-dopa Captopril Carbimazole Chlorpromazine Dihydralazine Fludarabine Hydralazine Infliximab Interferons-alpha Iproniazid Isoniazid Nomifensine Penicillamine D-Penicillamine Practolol Procainamide Propylthiouracil rlL-2 Simvastatin Tienilic acid Tryptophan contaminants Zimeldine Lupus syndrome Autoimmune haemolytic anaemia Pemphigus ANCA-associated vasculitis Lupus syndrome Autoimmune hepatitis Autoimmune haemolytic anaemia Lupus syndrome, ANCA-associated vasculitis Lupus syndrome Wide range of autoimmune diseases Autoimmune hepatitis Lupus syndrome Autoimmune haemolytic anaemia Myasthenia, dermatomyositis Anti-GBM (Goodpasture) disease Oculocutaneomucous syndrome Lupus syndrome ANCA-associated vasculitis Autoimmune thyroiditis Lupus syndrome Autoimmune hepatitis Eosinophilia myalgia syndrome (see section 9.3.5) Guillain-Barre syndrome... 

In another case, a 39-year-old woman mistakenly took simvastatin for weight reduction and developed a bilateral leg compartment syndrome and acute renal insufficiency due to myonecrosis [60 ]. 

Strony J, Musliner TA, McCabe CH, Veltri E, Braunwald E, Califf RM. IMPROVE-IT Investigators. Rationale and design of IMPROVE-IT (IMProved Reduction of Outcomes Vytorin Efficacy International Trial) comparison of ezeti-mibe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes in patients with acute coronary syndromes. Am Heart J 2008 156(5) 826-32. 

Exercise There is moxmting evidence that exercise might exacerbate statin-related side effects such as myopathy [50]. The randomised, controlled trial with 37 subjects (exercise plus simvastatin n= 18 exercise only n= 19) showed that simvastatin attenuates increases in cardiorespiratory fitness and skeletal muscle mitochondrial content when combined with exercise training in patients at risk of the metabolic syndrome [51]. The short-term administration of high-dose atorvastatin did not result in altered muscle function despite mild increases in creatine kinase levels [52]. 

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