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SIMVASTATIN

(brand name: Zocor)

Pharmacological category: antihyperlipidemic, HMG-CoA reductase inhibitor

Reviews
J Cereb Blood Flow Metab. 2005 Feb 16.
Protective effects of statins involving both eNOS and tPA in focal cerebral ischemia.
Asahi M, Huang Z, Thomas S, Yoshimura SI, Sumii T, Mori T, Qiu J, Amin-Hanjani S, Huang PL, Liao JK, Lo EH, Moskowitz MA.
1Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.

Previous studies have shown that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) protect the brain against ischemic injury by upregulating endothelial nitric oxide synthase (eNOS). Here, we tested the hypothesis that statins provide additional beneficial effects by also upregulating endogenous tissue plasminogen activator (tPA) and enhancing clot lysis in a mouse model of embolic focal ischemia. Heterologous blood clots (0.2 mm) were injected into the distal internal carotid artery to occlude blood flow in the middle cerebral artery territory after long-term (14 days) simvastatin, atorvastatin or vehicle treatment. Ischemic lesion volume, neurologic deficits, as well as residual blood clots were measured at 22 h. Reverse transcription-polymerase chain reaction assessed mRNA levels of eNOS, tPA, and the endogenous plasminogen activator inhibitor PAI-1. Ischemic lesion volumes and neurologic deficits were significantly reduced in wild-type mice by both simvastatin and atorvastatin. Statins increased eNOS and tPA mRNA levels but did not change mRNA levels of PAI-1. In eNOS knockout mice, atorvastatin reduced the volume of ischemic tissue and improved neurologic outcomes after arterial occlusion by blood clot emboli. In contrast, statins did not have protective effects in tPA knockout mice after embolic focal ischemia, but only in a filament model where focal ischemia was achieved via mechanical occlusion. These results suggest that statins protect against stroke by multiple mechanisms involving both eNOS and tPA. The involvement of each pathway may be revealed depending on the choice of experimental stroke model.Journal of Cerebral Blood Flow & Metabolism advance online publication, 16 February 2005; doi:10.1038/sj.jcbfm.9600070.
Clin Rheumatol. 2005 Mar 2.
Effects of simvastatin on bone mineral density and remodeling parameters in postmenopausal osteopenic subjects: 1-year follow-up study.
Tikiz C, Tikiz H, Taneli F, Gumuser G, Tuzun C.
Department of Physical Medicine and Rehabilitation, Faculty of Medicine, University of Celal Bayar, Manisa, Turkey.

Observational studies suggest that statin use may be associated with lower incidence of fracture. However, there are conflicting data for their effects on bone remodeling parameters and bone mineral density (BMD). In the present study, we aimed to investigate the effects of simvastatin on bone metabolism and BMD in subjects with hypercholesterolemia (>240 mg/dl). For this purpose, 32 postmenopausal osteopenic subjects who were given simvastatin treatment (20 mg/day) and not on osteoporosis treatment were included in the study. During the 1-year follow-up period, the total cholesterol level decreased from 262.1+/-30.9 to 202.2+/-30.1 mg/dl (p<0.0001). At a period as early as the 3rd month, levels of the anabolic markers, e.g., bone-specific alkaline phosphatase (BSAP) and osteocalcin (OCL), were found to be significantly increased (from 120.8+/-56.6 to 149.5+/-57.6 IU/l, p=0.008, and from 20.8+/-12.6 to 34.7+/-18.4 mug/l, p=0.015, respectively) while no significant change was observed in the resorptive marker of serum N-telopeptide of type I collagen (CTX). At the 6th and 12th month, BSAP and OCL were both found to be decreased below the pretreatment values. While a significant reduction was found in BSAP levels (from 120.8+/-56.6 to 55.9+/-18.8 IU/l, p<0.001), no significant change was observed in CTX levels after the 6-month treatment period. Parathyroid hormone showed a gradual profound increase during the follow-up period (from 62.7+/-41.5 to 108.4+/-51.7 pg/ml, p<0.001). No significant change was found in BMD levels at the spine, femoral neck, Ward's triangle, and trochanter at the end of the 1-year follow-up period. In conclusion, simvastatin treatment showed a short-lasting anabolic effect on bone metabolism. However, this effect was lost by prolongation of therapy. The decrease in both anabolic and resorptive markers at the 6th and 12th month suggests that simvastatin affects bone metabolism mostly in favor of inhibition of the bone turnover in a long-term observation period although this inhibitory effect was not reflected in BMD.

Am J Cardiol 2001 Aug 16;88(4 Suppl):10F-5F.
Are we aggressive enough in lowering cholesterol?
Waters DD.
Cardiology Division, Department of Medicine, San Francisco General Hospital, San Francisco, California 94110, USA.

To date, 5 major randomized, placebo-controlled statin trials--the Scandinavian Simvastatin Survival Study, West of Scotland Coronary Prevention Study, Cholesterol and Recurrent Events trial, Long-term Intervention with Pravastatin in Ischaemic Disease, and Air Force/Texas Coronary Atherosclerosis Prevention Study--have convincingly shown that total mortality and major coronary events can be significantly reduced by lowering levels of low-density lipoprotein cholesterol (LDL-C) with statin therapy. These results were achieved in a broad range of patients including those with and without a history of coronary artery disease and with elevated or average LDL-C levels. The results also support the large body of epidemiologic evidence demonstrating that the lower the cholesterol level, the lower the cardiovascular risk. Evidence now substantially supports the urgency of physicians to aggressively target the lowering of LDL-C levels for the primary and secondary prevention of coronary disease.

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Drug information

GENERIC NAME: simvastatin
BRAND NAME: Zocor


DRUG CLASS AND MECHANISM: Simvastatin is a cholesterol- lowering medicine. It inhibits the production of cholesterol by the liver. It lowers overall blood cholesterol as well as blood LDL cholesterol levels. LDL cholesterol is believed to be the "bad" cholesterol that is primarily responsible for the development of coronary artery disease. Lowering LDL cholesterol levels retards progression and may even reverse coronary artery disease.

PREPARATIONS: tablets: 5 mg,10 mg, 20 mg, 40 mg

STORAGE: Tablets should be stored at room temperature in a tightly closed container.

PRESCRIBED FOR: High blood cholesterol is first treated with exercise, weight loss, and a diet low in cholesterol and saturated fats. When these measures fail, cholesterol-lowering medications such as simvastatin can be added. The National Cholesterol Education Program (NCEP) has published treatment guidelines for use of these medications. These treatment guidelines take into account the level of LDL cholesterol as well as the presence of other risk factors such as diabetes, hypertension, cigarette smoking, low HDL cholesterol level, and family history of early coronary heart disease. The effectiveness of the medication in lowering cholesterol is dose related. Blood cholesterol determinations are performed in regular intervals during treatment so that dosage adjustments can be made.

DOSING: May be taken on an empty or full stomach.

DRUG INTERACTIONS: Simvastatin is generally well- tolerated. The medication should be used with caution in patients with alcohol or other liver diseases. Persistently abnormal liver tests during treatment are rare, but may lead to a discontinuation of the medication. Rare cases of muscle inflammation (myositis) and breakdown have been reported with simvastatin. Muscle breakdown causes the release of muscle protein (myoglobin) into the blood and kidney tubules, resulting in acute kidney failure. The risk of muscle breakdown is increased when simvastatin is given together with other medications such as cyclosporine (Sandimmune), gemfibrozil (Lopid), erythromycin and nicotinic acid. Simvastatin may interact with cholestyramine (Questran), warfarin (Coumadin), and cimetidine (Tagamet) to alter the blood levels of these medicines. When Coumadin is given together with simvastatin, blood clotting times require monitoring to avoid excessive blood thinning and bleeding. Simvastatin should not be used in children. Simvastatin is not habit forming.

PREGNANCY: Simvastatin should not be used by pregnant women.

NURSING MOTHERS: Simvastatin should not be used by nursing mothers because of potential adverse side effects to the nursing infant.

SIDE EFFECTS: Simvastatin is generally well-tolerated and side effects are rare. Minor side effects include constipation, diarrhea, fatigue, gas, heartburn, and headache. Major side effects include abdominal pain or cramps, blurred vision, dizziness, easy bruising or bleeding, itching, muscle pain or cramps, rash, and yellowing of the skin or eyes.

Caution! Before starting to take this medicine, it is vital that you should consult your doctor! Do not use it on your own initiative, without medical advice.
Also, you should read carefully important health information about this drug given here:


www.nlm.nih.gov
my.webmd.com

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ZOCOR
Substance: Simvastatin
Manufacturer: Merck & Co., INC.

Dosage
Packing
Price
Pay now
10 mg
28 tab
USD 39.00
10 mg
84 tab
USD 115.00
20 mg
28 tab
USD 59.00
20 mg
84 tab
USD 169.00

ZOCOR - GENERIC (generic - what is it?)
Substance: Simvastatin
Manufactured in India

 
Dosage
Packing
Price
Pay now
10 mg
30 caps
USD 29.00
10 mg
60 caps
USD 59.00
10 mg
90 caps
USD 74.00
20 mg
30 caps
USD 34.00
20 mg
60 caps
USD 63.00
20 mg
90 caps
USD 99.00
 

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