query: statins is the name given to a group of which type of drugs

pos: Statin Statin Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications. Statins have been found to reduce cardiovascular disease and mortality in those who are at high risk of cardiovascular disease. The evidence is strong that statins are effective for treating cardiovascular disease in the early stages of the disease (secondary prevention) and in those at elevated risk but without cardiovascular disease (primary prevention). Side effects of statins include muscle pain, increased risk of diabetes mellitus, and abnormalities in liver enzyme tests. Additionally, they have rare but severe adverse effects, particularly muscle damage. They inhibit the enzyme

neg: Discovery and development of statins 2 statins. One of the main differences between the type 1 and type 2 statins is the replacement of the butyryl group of type 1 statins by the fluorophenyl group of type 2 statins. This group is responsible for additional polar interactions that causes tighter binding to the HMGR enzyme. Statins that belong to this group are: Lovastatin is derived from a fungus source and simvastatin and pravastatin are chemical modifications of lovastatin and as a result do not differ much in structure from lovastatin. All three are partially reduced napthylene ring structures. Simvastatin and lovastatin are inactive lactones which

neg: Discovery and development of statins 3R,5R stereochemistry. The statins differ with respect to their ring structure and substituents. These differences in structure affect the pharmacological properties of the statins, such as: Statins have sometimes been grouped into two groups of statins according to their structure. Type 1 statins Statins that have substituted decalin-ring structure that resemble the first statin ever discovered, mevastatin have often been classified as type 1 statins due to their structural relationship. Statins that belong to this group are: Type 2 statins Statins that are fully synthetic and have larger groups linked to the HMG-like moiety are often referred to as type

neg: Bile acid sequestrant acid reabsorption will decrease cholesterol levels, in particular, low-density lipoprotein (commonly known as "bad cholesterol") in blood. Consequently, these drugs have been used for the treatment of hypercholesterolemia and dyslipidemia. Use of these agents as hypolipidemic agents has decreased markedly since the introduction of the statins, which are more efficacious than bile acid sequestrants at lowering LDL. They are occasionally used as an adjunct to the statins as an alternative to the fibrates (another major group of cholesterol-lowering drugs), which are thought to increase the risk of rhabdomyolysis when used with statins. The bile-acid-binding resins can raise triglycerides modestly (about

neg: Discovery and development of statins electronegative sulfone group on rosuvastatin makes it the statin that has the greatest number of bonding interactions with HGMR. All statins have the same pharmacophore so the difference in their pharmacodynamic effect is mostly based on the substituents. The activity of each statin is dependent on the binding affinity of the compound for the substrate site and the length of time it binds to the site. Type 2 statins have unique fluorophenyl group that causes additional polar interaction between the enzyme and the statins, which results in a tighter binding to the enzyme. The newest statin, rosuvastatin has a unique

neg: Discovery and development of statins Asp and the O5 hydroxyl group of the hydroxyglutartic acid component of the statins. Van der Waals interactions are formed between the hydrophobic side chains of the enzyme, which involve the Leu, Val, Leu, Ala and Leu and the statins. Type 2 statins form polar interaction between the fluorine atom on the fluorophenyl group and the guanidinium group of Arg. In addition to these interactions atorvastatin and rosuvastatin also form unique hydrogen bonds between Ser residue and either a carbonyl oxygen atom (atorvastatin) or a sulfone oxygen atom (rosuvastatin). A unique polar interaction between the Arg side chain and the

neg: Rosuvastatin infant's lipid metabolism, patients should not breast feed while on rosuvastatin. The following drugs can have negative interactions with rosuvastatin and should be discussed with the prescribing doctor: Rosuvastatin has structural similarities with most other synthetic statins, e.g., atorvastatin, cerivastatin and pitavastatin, but unlike other statins, rosuvastatin contains sulfur (in sulfonyl functional group). Crestor is actually a calcium salt of rosuvastatin, i.e. rosuvastatin calcium, in which calcium replaces the hydrogen in the carboxylic acid group on the right of the skeletal formula at the top right of this page. Rosuvastatin is a competitive inhibitor of the enzyme HMG-CoA reductase, having

neg: Statin certain statin drugs. Protease inhibitors and statins taken together may increase the blood levels of statins and increase the risk for muscle injury (myopathy). The most serious form of myopathy, rhabdomyolysis, can damage the kidneys and lead to kidney failure, which can be fatal. Statins act by competitively inhibiting HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway. Because statins are similar in structure to HMG-CoA on a molecular level, they will fit into the enzyme's active site and compete with the native substrate (HMG-CoA). This competition reduces the rate by which HMG-CoA reductase is able to produce mevalonate, the

neg: Combined hyperlipidemia (VLDL), a class of lipoproteins prone to cause atherosclerosis. The two forms of this lipid disorder are: Both conditions are treated with fibrate drugs, which act on the peroxisome proliferator-activated receptors (PPARs), specifically PPARα, to decrease free fatty acid production. Statin drugs, especially the synthetic statins (atorvastatin and rosuvastatin), can decrease LDL levels by increasing hepatic reuptake of LDL due to increased LDL-receptor expression. Combined hyperlipidemia Combined hyperlipidemia (or -aemia) (also known as multiple-type hyperlipoproteinemia) is a commonly occurring form of hypercholesterolemia (elevated cholesterol levels) characterised by increased LDL and triglyceride concentrations, often accompanied by decreased HDL. On lipoprotein electrophoresis

neg: Discovery and development of statins polar methane sulfonamide group, which is quite hydrophilic and confers low lipophilicity. The sulfonamide group forms a unique polar interaction with the enzyme. As a result, rosuvastatin has superior binding affinity to the HMGR enzyme compared to the other statins, which is directly related to its efficiency to lower LDL cholesterol. Lipophilicity of the statins is considered to be quite important since the hepatoselectivity of the statins is related to their lipophilicity. The more lipophilic statins tend to achieve higher levels of exposure in non-hepatic tissues, while the hydrophilic statins tend to be more hepatoselective. The difference in selectivity is

neg: Bad Pharma about which one is preferable to the extent that it could affect their health. In the final chapter, Goldacre looks at how doctors are persuaded to prescribe "me-too drugs," brand-name drugs that are no more effective than significantly cheaper off-patent ones. He cites as examples the statins atorvastatin (Lipitor, made by Pfizer) and simvastatin (Zocor), which he writes seem to be equally effective, or at least there is no evidence to suggest otherwise. Simvastatin came off patent several years ago, yet there are still three million prescriptions a year in the UK for atorvastatin, costing the National Health Service (NHS)

neg: Lovastatin the β-hydroxy acid open ring form; which is the active form. Lovastatin and other statins have been studied for their chemopreventive and chemotherapeutic effects. No such effects were seen in the early studies. More recent investigations revealed some chemopreventive and therapeutic effects, for certain types of cancer, especially in combination of statins with other anticancer drugs. It is likely that these effect are mediated by the properties of statins to reduce proteasome activity, leading to an accumulation of cyclin-dependent kinase inhibitors p21 and p27, and to subsequent G-phase arrest, as seen in cells of different cancer lines. Compactin and lovastatin,

neg: Cholestasis Cholestasis Cholestasis is a condition where bile cannot flow from the liver to the duodenum. The two basic distinctions are an obstructive type of cholestasis where there is a mechanical blockage in the duct system that can occur from a gallstone or malignancy, and metabolic types of cholestasis which are disturbances in bile formation that can occur because of genetic defects or acquired as a side effect of many medications. Possible causes: Drugs such as gold salts, nitrofurantoin, anabolic steroids, chlorpromazine, prochlorperazine, sulindac, cimetidine, erythromycin, estrogen, and statins can cause cholestasis and may result in damage to the liver. Bile

neg: Pharmacogenomics for physicians and care givers to better manage medication selection and side effect amelioration. Pharmacogenomics is also known as companion diagnostics, meaning tests being bundled with drugs. Examples include KRAS test with cetuximab and EGFR test with gefitinib. Beside efficacy, germline pharmacogenetics can help to identify patients likely to undergo severe toxicities when given cytotoxics showing impaired detoxification in relation with genetic polymorphism, such as canonical 5-FU. In cardiovascular disorders, the main concern is response to drugs including warfarin, clopidogrel, beta blockers, and statins. "Case A – Antipsychotic adverse reaction" Patient A suffers from schizophrenia. Their treatment included a combination

neg: Statin other pleiotropic cardiovascular benefits of statins, as well as in the fact that a number of other drugs that lower LDL have not shown the same cardiovascular risk benefits in studies as statins, and may also account for certain of the benefits seen in cancer reduction with statins. In addition, the inhibitory effect on protein prenylation may also be involved in a number of unwanted side effects associated with statins, including muscle pain (myopathy) and elevated blood sugar (diabetes). As noted above, statins exhibit action beyond lipid-lowering activity in the prevention of atherosclerosis. The ASTEROID trial showed direct ultrasound evidence

neg: Simvastatin ml) of grapefruit juice per day. Simvastatin also interacts with other drugs, including some used to treat cardiovascular problems. It should not be taken by people who are also taking the antifungal drugs fluconazole, itraconazole, or posaconazole; the antibiotics erythromycin, clarithromycin, or telithromycin; HIV protease inhibitors; the antidepressant nefazodone; the cardiovascular drug gemfibrozil; the immunosuppressant ciclosporin, or the endometriosis drug danazol. Reduced maximum doses of simvastatin apply for patients taking certain other drugs, including the cardiovascular drugs verapamil, diltiazem, amiodarone, amlodipine, and ranolazine.<ref name="urlInformation on Simvastatin/Amiodarone"></ref> All statins act by inhibiting 3-hydroxy-3-methylglutaryl (HMG) coenzyme A reductase. HMG-CoA reductase, the rate-limiting

neg: Simvastatin enzyme of the HMG-CoA reductase pathway, the metabolic pathway responsible for the endogenous production of cholesterol. Statins are more effective than other lipid-regulating drugs at lowering LDL-cholesterol concentration, but they are less effective than the fibrates in reducing triglyceride concentration. However, statins reduce cardiovascular disease events and total mortality irrespective of the initial cholesterol concentration. This is a major piece of evidence that statins work in another way than the lowering of cholesterol (called pleiotropic effects). The drug is in the form of an inactive lactone that is hydrolyzed after ingestion to produce the active agent. It is a white,

neg: Mevalonic acid Mevalonic acid Mevalonic acid (MVA) is a key organic compound in biochemistry; the name is a contraction of dihydroxymethylvalerolactone. The carboxylate anion of mevalonic acid, which is the predominant form in biological environments, is known as "mevalonate" and is of major pharmaceutical importance. Drugs like statins (which lower levels of cholesterol) stop the production of mevalonate by inhibiting HMG-CoA reductase. Mevalonic acid is very soluble in water and polar organic solvents. It exists in equilibrium with its lactone form, called mevalonolactone, that is formed by internal condensation of its terminal alcohol and carboxylic acid functional groups. Mevalonic acid is a

neg: Fluvastatin Fluvastatin Fluvastatin (INN, trade names Lescol, Canef, Vastin) is a member of the statin drug class, used to treat hypercholesterolemia and to prevent cardiovascular disease. Adverse effects are comparable to other statins. Common are nausea, indigestion, insomnia and headache. Myalgia (muscle pain), and rarely rhabdomyolysis, characteristic side effects for statins, can also occur. Contrary to lovastatin, simvastatin and atorvastatin, fluvastatin has no relevant interactions with drugs that inhibit the liver enzyme CYP3A4, and a generally lower potential for interactions than most other statins. Fluconazole, a potent inhibitor of CYP2C9, does increase fluvastatin levels. Fluvastatin works by blocking the liver enzyme

neg: Hyperglycerolemia by a mutation or deletion of an individual's genetic code. In adults, fibrates and statins have been prescribed to treat hyperglycerolemia by lowering blood glycerol levels. Fibrates are a class of drugs that are known as amphipathic carboxylic acids that are often used in combination with Statins. Fibrates work by lowering blood triglyceride concentrations. When combined with statins, the combination will lower LDL cholesterol, lower blood triglycerides and increase HDL cholesterol levels. If hyperglycerolemia is found in a young child without any family history of this condition, then it may be difficult to know whether the young child has the

neg: Pitavastatin pathway that all statin drugs inhibit). Pitavastatin appears to have improved tolerably in its metabolic profile, with a neutral effect on glucose regulation, as opposed to many statins. As opposed to other statins, there is evidence that pitavastatin improves insulin resistance in humans, with insulin resistance assessed by the homeostatic model assessment (HOMA-IR) method. Hyperuricemia or increased levels of serum uric acid have been reported with pitavastatin. Most statins are metabolised in part by one or more hepatic cytochrome P450 enzymes, leading to an increased potential for drug interactions and problems with certain foods (such as grapefruit juice). The primary

neg: Discovery and development of statins must be metabolized to their active hydroxy-acid forms in order to inhibit HMGR. Type 2 statins all exist in their active hydroxy-acid forms. Fluvastatin has indole ring structure, while atorvastatin and rosuvastatin have pyrrole and pyrimidine based ring structure respectively. The lipophilic cerivastatin has a pyridine-based ring structure. Studies have shown that statins bind reversibly to the HGMR enzyme. The affinity of statins for HGMR enzyme is in the nanomolar range, while the natural substrate's affinity is in the micromolar range. Studies have shown that statins use the conformational flexibility of the HMGR enzyme that causes a shallow hydrophobic groove

neg: Stanol ester understood. Stanol ester Stanol ester is a heterogeneous group of chemical compounds known to reduce the level of low-density lipoprotein (LDL) cholesterol in blood when ingested, though to a much lesser degree than prescription drugs such as statins. The starting material is phytosterols from plants. These are first hydrogenated to give a plant stanol which is then esterified with a mixture of fatty acids also derived from plants. Plant stanol esters are found naturally occurring in small quantities in fruits, vegetables, nuts, seeds, cereals, legumes, and vegetable oils. Stanol ester is often added to rapeseed oil based margarine or other

neg: Stanol ester Stanol ester Stanol ester is a heterogeneous group of chemical compounds known to reduce the level of low-density lipoprotein (LDL) cholesterol in blood when ingested, though to a much lesser degree than prescription drugs such as statins. The starting material is phytosterols from plants. These are first hydrogenated to give a plant stanol which is then esterified with a mixture of fatty acids also derived from plants. Plant stanol esters are found naturally occurring in small quantities in fruits, vegetables, nuts, seeds, cereals, legumes, and vegetable oils. Stanol ester is often added to rapeseed oil based margarine or other foods

neg: HMG-CoA reductase contemporary cholesterol-lowering drugs in humans. The medical significance of HMG-CoA reductase has continued to expand beyond its direct role in cholesterol synthesis following the discovery that statins can offer cardiovascular health benefits independent of cholesterol reduction. Statins have been shown to have anti-inflammatory properties, most likely as a result of their ability to limit production of key downstream isoprenoids that are required for portions of the inflammatory response. It can be noted that blocking of isoprenoid synthesis by statins has shown promise in treating a mouse model of multiple sclerosis, an inflammatory autoimmune disease. HMG-CoA reductase is an important developmental

neg: Mevalonic acid precursor in the biosynthetic pathway known as the mevalonate pathway that produces terpenes and steroids. Mevalonic acid is the primary precursor of isopentenyl pyrophosphate (IPP), that is in turn the basis for all terpenoids. Mevalonic acid is chiral and the (3"R")-enantiomer is the only one that is biologically active. Mevalonic acid Mevalonic acid (MVA) is a key organic compound in biochemistry; the name is a contraction of dihydroxymethylvalerolactone. The carboxylate anion of mevalonic acid, which is the predominant form in biological environments, is known as "mevalonate" and is of major pharmaceutical importance. Drugs like statins (which lower levels of cholesterol)

neg: Pleiotropy (drugs) can respond to them, because the endogenous ones are endocrine messengers. Pleiotropy (drugs) In pharmacology, pleiotropy includes all of a drug's actions other than those for which the agent was specifically developed. It may include adverse effects which are detrimental ones, but is often used to denote additional beneficial effects. For example, statins are HMG-CoA reductase inhibitors that primarily act by decreasing cholesterol synthesis, but which are believed to have other beneficial effects, including acting as antioxidants and stabilizing atherosclerotic plaques. Steroid drugs, such as prednisone and prednisolone, have pleiotropic effects, including systemic ones, for the same reason that endogenous

neg: Hyperlipidemia most common causes of acquired hyperlipidemia are: Other conditions leading to acquired hyperlipidemia include: Treatment of the underlying condition, when possible, or discontinuation of the offending drugs usually leads to an improvement in the hyperlipidemia. Another acquired cause of hyperlipidemia, although not always included in this category, is postprandial hyperlipidemia, a normal increase following ingestion of food. Testing the general population under the age of 40 without symptoms is of unclear benefit. For treatment of type II, dietary modification is the initial approach, but many patients require treatment with statins (HMG-CoA reductase inhibitors) to reduce cardiovascular risk. If the triglyceride

neg: Mevalonate pathway Mevalonate pathway The mevalonate pathway, also known as the isoprenoid pathway or HMG-CoA reductase pathway is an essential metabolic pathway present in eukaryotes, archaea, and some bacteria. The pathway produces two five-carbon building blocks called isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are used to make isoprenoids, a diverse class of over 30,000 biomolecules such as cholesterol, heme, vitamin K, coenzyme Q10, and all steroid hormones. The mevalonate pathway begins with acetyl-CoA and ends with the production of IPP and DMAPP. It is best known as the target of statins, a class of cholesterol lowering drugs. Statins inhibit HMG-CoA

neg: Pleiotropy (drugs) Pleiotropy (drugs) In pharmacology, pleiotropy includes all of a drug's actions other than those for which the agent was specifically developed. It may include adverse effects which are detrimental ones, but is often used to denote additional beneficial effects. For example, statins are HMG-CoA reductase inhibitors that primarily act by decreasing cholesterol synthesis, but which are believed to have other beneficial effects, including acting as antioxidants and stabilizing atherosclerotic plaques. Steroid drugs, such as prednisone and prednisolone, have pleiotropic effects, including systemic ones, for the same reason that endogenous steroid hormones do too: cells throughout the body have receptors that

neg: HMG-CoA reductase used to lower serum cholesterol as a means of reducing the risk for cardiovascular disease. These drugs include rosuvastatin (CRESTOR), lovastatin (Mevacor), atorvastatin (Lipitor), pravastatin (Pravachol), fluvastatin (Lescol), pitavastatin (Livalo), and simvastatin (Zocor). Red yeast rice extract, one of the fungal sources from which the statins were discovered, contains several naturally occurring cholesterol-lowering molecules known as monacolins. The most active of these is monacolin K, or lovastatin (previously sold under the trade name Mevacor, and now available as generic lovastatin). Vytorin is drug that combines the use simvastatin and ezetimibe, which slows the formation of cholesterol by every cell in

neg: Combretastatin Combretastatin Combretastatin is a dihydrostilbenoid found in "Combretum caffrum". Combretastatins are a class of natural phenols. A variety of different natural combretastatin molecules are present in the bark of "Combretum caffrum", commonly known as South African Bush Willow. Despite having a similar name, combretastatins are unrelated to statins, a family of cholesterol lowering drugs. Molecules that fall into the combretastatin family generally share 3 common structural features: a trimethoxy "A"-ring, a "B"-ring containing substituents often at C3' and C4', and [often] an ethene bridge between the two rings which provides necessary structural rigidity. Molecules with such an ethene bridge are

neg: Acute tubular necrosis excretion of sodium) > 3% and presence of muddy casts (a type of granular cast) in urinalysis. On histopathology, there is usually "tubulorrhexis", that is, localized necrosis of the epithelial lining in renal tubules, with focal rupture or loss of basement membrane. Proximal tubule cells can shed with variable viability and not be purely "necrotic". Toxic ATN can be caused by free hemoglobin or myoglobin, by medication including antibiotics such as aminoglycoside, statins such as atorvastatin, and cytotoxic drugs such as cisplatin, or by intoxication (ethylene glycol, "anti-freeze"). Histopathology: Toxic ATN is characterized by proximal tubular epithelium necrosis (no nuclei,

neg: Statin A common variation in this gene was found in 2008 to significantly increase the risk of myopathy. Records exist of over 250,000 people treated from 1998 to 2001 with the statin drugs atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, and simvastatin. The incidence of rhabdomyolyis was 0.44 per 10,000 patients treated with statins other than cerivastatin. However, the risk was over 10-fold greater if cerivastatin was used, or if the standard statins (atorvastatin, fluvastatin, lovastatin, pravastatin, or simvastatin) were combined with a fibrate (fenofibrate or gemfibrozil) treatment. Cerivastatin was withdrawn by its manufacturer in 2001. Some researchers have suggested hydrophilic statins, such

neg: Kiran Mazumdar-Shaw noticed the market potential for statins (cholesterol fighting drugs) early on. When the patent of the cholesterol-lowering drug lovastatin expired in 2001, Biocon got involved in its development. Then they expanded to other forms of statins. Part of her strategy was to enter into long-term supply contracts, establishing a dependable market base over time. Statins soon accounted for over 50 per cent of the company's revenue. The company’s revenue went up from Rs. 70 crore in 1998, to Rs. 500 crore in 2004 when it went public. Biocon continues to expand into new areas. Yeast expression platforms offer a desirable

neg: High-density lipoprotein did experience an increase in the risk of stroke. In contrast, while the use of statins is effective against high levels of LDL cholesterol, most have little or no effect in raising HDL cholesterol. However, several statins – rosuvastatin and pitavastatin – have been demonstrated to significantly raise HDL levels. As statins are associated with side effects like myopathy which causes sore muscles, patients who experience these side effects may need to be given a lower dose of statin to control cholesterol. Lovaza has been shown to increase HDL-C. However, the best evidence to date suggests it has no benefit

neg: BaleDoneen Method method uses pharmaceuticals such as statins, baby aspirin (low-dose aspirin), renin–angiotensin–aldosterone system inhibitors (RAAS inhibitors), and other drugs that are common tools for most physicians, as well as vitamins, supplements, lifestyle modification, and a diet based on the patient’s DNA. BaleDoneen Method The BaleDoneen Method is an evidence-based, comprehensive risk assessment and treatment protocol for patients designed to prevent cardiovascular disease, heart attack, and stroke, and for treatment designed to prevent disease progression and repeat heart attacks or strokes after one of these medical events. The method also aims to prevent or reduce the effects of type 2 diabetes, technically

neg: Chronic endothelial injury hypothesis the hypertension often seen with atherosclerosis. The role LDL plays suggests two different approaches to treatment and prevention. The first approach involves discouraging the accumulation of LDL by lowering the levels of serum LDL, an idea more closely associated with the lipid hypothesis. A major breakthrough involved the discovery of statins, a class of drugs which help to clear LDL from the bloodstream. It has been demonstrated conclusively that elevated levels of LDL are associated with higher risk of mortality from coronary heart disease (CHD); it has also been shown that statins substantially lower the risk of mortality in patients

neg: Chloramphenicol although concerns over aplastic anaemia associated with ocular chloramphenicol have largely been discounted. Chloramphenicol is a potent inhibitor of the cytochrome P450 isoforms CYP2C19 and CYP3A4 in the liver. Inhibition of CYP2C19 causes decreased metabolism and therefore increased levels of, for example, antidepressants, antiepileptics, proton-pump inhibitors, and anticoagulants if they are given concomitantly. Inhibition of CYP3A4 causes increased levels of, for example, calcium channel blockers, immunosuppressants, chemotherapeutic drugs, benzodiazepines, azole antifungals, tricyclic antidepressants, macrolide antibiotics, SSRIs, statins, cardiac antiarrhythmics, antivirals, anticoagulants, and PDE5 inhibitors. Chloramphenicol is antagonistic with most cephalosporins and using both together should be avoided in the treatment

neg: Steroid fungi; see examples above) or cycloartenol (in plants). Lanosterol and cycloartenol derive from cyclization of the triterpenoid squalene. Steroid biosynthesis is an anabolic pathway which produces steroids from simple precursors. A unique biosynthetic pathway is followed in animals (compared to many other organisms), making the pathway a common target for antibiotics and other anti-infection drugs. Steroid metabolism in humans is also the target of cholesterol-lowering drugs, such as statins. In humans and other animals the biosynthesis of steroids follows the mevalonate pathway, which uses acetyl-CoA as building blocks for dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP). In subsequent steps DMAPP

neg: Discovery and development of statins dominant. CYP3A4 isoenzyme is the most predominant isoform involved in metabolism of lovastatin, simvastatin, atorvastatin and cerivastatin. CYP2C9 isoenzyme is the most predominant isoform involved in metabolism of Fluvastatin, but CYP3A4 and CYP2C8 isoenzymes also contribute to the metabolism of Fluvastatin. Rosuvastatin is metabolized to a small degree by CYP2C9 and to a lesser extent by CYP2C19 isoenzymes. Pravastatin is not metabolized by CYP isoenzymes to any appreciable extent. The statins that have the ability to be metabolized by multiple CYP isoenzymes may therefore avoid drug accumulation when one of the pathways is inhibited by co-administered drugs. With the recent

neg: Bisphosphonate phenomenon). While inhibition of protein prenylation may affect many proteins found in an osteoclast, disruption to the lipid modification of Ras, Rho, Rac proteins has been speculated to underlie the effects of bisphosphonates. These proteins can affect both osteoclastogenesis, cell survival, and cytoskeletal dynamics. In particular, the cytoskeleton is vital for maintaining the "ruffled border" that is required for contact between a resorbing osteoclast and a bone surface. Statins are another class of drugs that inhibit the HMG-CoA reductase pathway. Unlike bisphosphonates, statins do not bind to bone surfaces with high affinity, and thus are not specific for bone. Nevertheless,

neg: Comorbidity did not kill the pain. It was also known from the case history that the patient had twice suffered during the last ten years from myocardial infarction, as well as from Acute Cerebrovascular Event with sinistral hemiplegia more than 15 years ago. Apart from that the patient suffers from hypertension, type 2 diabetes with diabetic nephropathy, hysteromyoma, cholelithiasis, osteoporosis and varicose pedi-vein disease. It also came to knowledge that the patient regularly takes a number of antihypertensive drugs, urinatives and oral antihyperglycemic remedies, as well as statins, antiplatelet and nootropics. In the past the patient had undergone cholecystectomy due to

neg: Kalipada Pahan from the UNMC College of Dentistry. He also received the Zenith Fellows Award from the Alzheimer's Association. Kalipada Pahan Kalipada Pahan is a Professor of Neurological Sciences, Biochemistry and Pharmacology, and the Floyd A. Davis, M.D., Endowed Chair in Neurology in Rush University Medical Center. He is also a Veterans Affairs (VA) Scientist at the Jesse Brown VA Medical Center. He is an eminent Indian American neuroscientist involved in translational research on multiple sclerosis, Parkinson's disease, Alzheimer's disease, dementia, and Batten disease. He is known for his research on statins, cholesterol-lowering drugs. He first explored the application of statins in

neg: Kalipada Pahan Kalipada Pahan Kalipada Pahan is a Professor of Neurological Sciences, Biochemistry and Pharmacology, and the Floyd A. Davis, M.D., Endowed Chair in Neurology in Rush University Medical Center. He is also a Veterans Affairs (VA) Scientist at the Jesse Brown VA Medical Center. He is an eminent Indian American neuroscientist involved in translational research on multiple sclerosis, Parkinson's disease, Alzheimer's disease, dementia, and Batten disease. He is known for his research on statins, cholesterol-lowering drugs. He first explored the application of statins in suppressing the inflammatory events in microglia, astroglia and macrophages. This finding has revolutionized the research on statin

neg: Coenzyme Q10 be measured in blood plasma, these measurements reflect dietary intake rather than tissue status. Currently, most clinical centers measure CoQ levels in cultured skin fibroblasts, muscle biopsies, and blood mononuclear cells. Culture fibroblasts can be used also to evaluate the rate of endogenous CoQ biosynthesis, by measuring the uptake of C-labelled "p"-hydroxybenzoate. CoQ shares a biosynthetic pathway with cholesterol. The synthesis of an intermediary precursor of CoQ, mevalonate, is inhibited by some beta blockers, blood pressure-lowering medication, and statins, a class of cholesterol-lowering drugs. Statins can reduce serum levels of CoQ by up to 40%. CoQ is not approved by

neg: Juvenile hormone CoASH as substrates. Three acetyl-CoAs are converted inoto HMG-CoA by the cytosolic isoforms of thiolase and 3-hydroxy-3-methylglutaryl-CoA synthase. The HMG-CoA is then reduced by NADPH to mevalonate by HMG-CoA reductase, the rate controlling enzyme of cholesterol biosynthesis. This enzyme has 8 helical domains anchoring it in the Golgi membrane of the ER; the catalytic domain is in the cytosol. It is strongly inhibited by the statins, a class of drugs based on a mold metabolite which, at least at one time, were the largest selling class of drugs in the world. Mevalonate is acted of by a series of 3

neg: Endothelial NOS of diseases with NOS3 haplotypes (combination of alleles in close proximity, within a DNA block). This approach may be more informative than the analysis of genetic polymorphisms one by one. Haplotypes including the SNPs g.-786T>C and Glu298Asp and the VNTR in intron 4 affected the susceptibility to hypertension, preeclampsia, and hypertension in diabetic subjects, NOS3 variants may also affect the responses to drugs that affect NO signaling, such as statins, angiotensin-converting enzyme inhibitors (ACEi) and phosphodiesterase type 5 (PDE-5) inhibitors (PDE5i). Statin treatment was more effective in increasing NO bioavailability in subjects carrying the CC genotype for the g.-786T>C polymorphism

neg: Enzyme pathways such as the citric acid cycle make use of this mechanism. Since inhibitors modulate the function of enzymes they are often used as drugs. Many such drugs are reversible competitive inhibitors that resemble the enzyme's native substrate, similar to methotrexate above; other well-known examples include statins used to treat high cholesterol, and protease inhibitors used to treat retroviral infections such as HIV. A common example of an irreversible inhibitor that is used as a drug is aspirin, which inhibits the COX-1 and COX-2 enzymes that produce the inflammation messenger prostaglandin. Other enzyme inhibitors are poisons. For example, the poison

neg: Discovery and development of statins trials showed very good inhibitory effect as in clinical trials, however in a long term toxicity study in dogs it resulted in toxic effects at higher doses and as a result was believed to be too toxic to be given to humans. In 1978, Alfred Alberts and colleagues at Merck Research Laboratories discovered a new natural product in a fermentation broth of "Aspergillus terreus", their product showed good HMGR inhibition and they named the product mevinolin, which later became known as lovastatin. The cholesterol controversy began in the early promotion of statins. Statins are a competitive antagonists of HMG CoA,

neg: Statin and possibly prostate cancer. They appear to have no effect on the risk of lung cancer, kidney cancer, breast cancer, pancreatic cancer, or bladder cancer. Combining any statin with a fibrate or niacin (other categories of lipid-lowering drugs) increases the risks for rhabdomyolysis to almost 6.0 per 10,000 person-years. Monitoring liver enzymes and creatine kinase is especially prudent in those on high-dose statins or in those on statin/fibrate combinations, and mandatory in the case of muscle cramps or of deterioration in kidney function. Consumption of grapefruit or grapefruit juice inhibits the metabolism of certain statins. Bitter oranges may have a

neg: Medicinal fungi the fungal metabolite pleuromutilin. Plectasin, austrocortilutein, austrocortirubin, coprinol, oudemansin A, strobilurin, illudin, pterulone, and sparassol are antibiotics isolated from basidiomycete species. Statins are an important class of cholesterol-lowering drugs; the first generation of statins were derived from fungi. The Pravastatin precursor mevastatin can be extracted from "Penicillium". Lovastatin, the first commercial statin, was extracted from a fermentation broth of "Aspergillus terreus". Industrial production is now capable of producing 70 mg lovastatin per kilogram of substrate. The red yeast rice fungus, "Monascus purpureus", can synthesize lovastatin, mevastatin, and the simvastatin precursor monacolin J. Zaragozic acids were isolated from ascomycota. Nicotinamide riboside,

neg: Pharmaceutical sales representative flattery, the attractiveness of sales reps has been noted, with a trend of former cheerleaders entering the field. Researchers note; "seduction appeared to be a deliberate industry strategy", and in informal survey by a doctor found that 12 out of 13 women sales reps said they had been sexually harassed by doctors. Sales reps push new "follow on" or "me-too" drugs with free samples that are more expensive than existing generic drugs, such as Nexium which costs three times as much as its predecessor Prilosec, with no evidence of improved efficacy. With beta-blockers and statins, me-too drugs have improved results,

neg: Lanosterol synthase disease prevention and treatment (see Disease Relevance, below). Interest has grown in lanosterol synthase inhibitors as drugs to lower blood cholesterol and treat atherosclerosis. The widely popular statin drugs currently used to lower LDL (low-density lipoprotein) cholesterol function by inhibiting HMG-CoA reductase activity. Because this enzyme catalyzes the formation of precursors far upstream of (S)-2,3-epoxysqualene and cholesterol, statins may negatively influence amounts of intermediates required for other biosynthetic pathways (e.g. synthesis of isoprenoids, coenzyme Q). Thus, lanosterol synthase, which is more closely tied to cholesterol biosynthesis than HMG-CoA reductase, is an attractive drug target. Lanosterol synthase inhibitors are thought to

neg: Ezetimibe 1.7-fold, 3-to-4-fold, and 5-to-6-fold, respectively, compared to healthy subjects. Ezetimibe Ezetimibe is a drug that lowers plasma cholesterol levels. It acts by decreasing cholesterol absorption in the small intestine. It may be used alone (marketed as Zetia or Ezetrol), when other cholesterol-lowering medications are not tolerated, or together with statins (e.g., ezetimibe/simvastatin, marketed as Vytorin or Inegy) when statins alone do not control cholesterol. Ezetimibe is recommended as second line therapy for those intolerant of statins or unable to achieve target low-density lipoprotein (LDL) cholesterol levels on statins alone by several major medical group practice guidelines, including the American College

neg: Ezetimibe Ezetimibe Ezetimibe is a drug that lowers plasma cholesterol levels. It acts by decreasing cholesterol absorption in the small intestine. It may be used alone (marketed as Zetia or Ezetrol), when other cholesterol-lowering medications are not tolerated, or together with statins (e.g., ezetimibe/simvastatin, marketed as Vytorin or Inegy) when statins alone do not control cholesterol. Ezetimibe is recommended as second line therapy for those intolerant of statins or unable to achieve target low-density lipoprotein (LDL) cholesterol levels on statins alone by several major medical group practice guidelines, including the American College of Cardiology. In the United States as of 2015

neg: Pitavastatin As a consequence, pitavastatin is likely to be appropriate for patients with metabolic syndrome plus high LDL, low HDL and diabetes mellitus. Common statin-related side effects (headaches, stomach upset, abnormal liver function tests and muscle cramps) were similar to other statins. However, pitavastatin seems to lead to fewer muscle side effects than certain statins that are lipid-soluble, as a result of the fact that pitavastatin is water-soluble (as is pravastatin, for example). One study found that coenzyme Q was not reduced as much as with certain other statins (though this is unlikely given the inherent chemistry of the HMG-CoA reductase

neg: RVX 208 international, multicenter phase III trial, “Effect of RVX000222 on Time to Major Adverse Cardiovascular Events in High-Risk Type 2 Diabetes Mellitus Subjects with Coronary Artery Disease” (BETonMACE) commenced in October 2015. The trial is designed to determine whether apabetalone in combination with statins can decrease cardiac events compared to treatment with statins alone. The molecular targets of apabetalone are bromodomain and extra terminal domain (BET) proteins, and in particular the BET family member BRD4. BET proteins, which contain two bromodomains, interact with acetylated lysines on histones bound to DNA to regulate gene transcription via an epigenetic mechanism. Apabetalone selectively binds

neg: Consumer Reports Best Buy Drugs category; and cost less on average than other drugs in the category. Several of the Best Buys have been chosen because of their superior effectiveness or safety profile even though they may cost more. The project publishes Best Buy Drugs drug reports, the first three such reports covered Statins to reduce high cholesterol, heartburn drugs, and NSAIDs commonly used to treat arthritis. The project covers over 20 conditions and the most widely used drugs. The reports are published in web versions, and two-page PDF summaries in English and Spanish. More than half of all prescription drugs cause adverse effects—some serious

neg: Triparanol accumulation of desmosterol, which in turn is responsible for the side effects of triparanol. Unlike statins, triparanol does not inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis, and in contrast to triparanol, statins can significantly lower cholesterol levels without resulting in accumulation of intermediates like desmosterol. The developmental code name of triparanol, MER/29, became so well known that it became the registered trade name of the drug. Estrogen is known to lower cholesterol levels, but produces side effects like gynecomastia and decreased libido in men. It was hoped that a drug could be developed that lacked overt estrogenic effects

neg: International nonproprietary name example: "paracetamol" (en) ' (la), ' (fr) and (ru). An established INN is known as a "recommended" INN (rINN), while a name that is still being considered is called a "proposed" INN (pINN). Drugs from the same therapeutic or chemical class are usually given names with the same "stem". Stems are mostly placed word-finally, but in some cases word-initial stems are used. They are collected in a publication informally known as the "Stem Book". Examples are: The term "stem" is not used consistently in linguistics. It has been defined as a form to which affixes (of any type) can be

neg: Fungus of bacterial diseases, such as tuberculosis, syphilis, leprosy, and others began in the early 20th century and continues to date. In nature, antibiotics of fungal or bacterial origin appear to play a dual role: at high concentrations they act as chemical defense against competition with other microorganisms in species-rich environments, such as the rhizosphere, and at low concentrations as quorum-sensing molecules for intra- or interspecies signaling. Other drugs produced by fungi include griseofulvin isolated from "Penicillium griseofulvum", used to treat fungal infections, and statins (HMG-CoA reductase inhibitors), used to inhibit cholesterol synthesis. Examples of statins found in fungi include mevastatin

neg: Atorvastatin Atorvastatin Atorvastatin, marketed under the trade name Lipitor among others, is a member of the medication class known as statins, which are used primarily as a lipid-lowering agent and for prevention of events associated with cardiovascular disease. Like all statins, atorvastatin works by inhibiting HMG-CoA reductase, an enzyme found in liver tissue that plays a key role in production of cholesterol in the body. Atorvastatin was first made in August 1985 at Warner-Lambert's Parke-Davis research facility in Ann Arbor, Michigan by a team led by Bruce Roth. From 1996 to 2012 under the trade name Lipitor, atorvastatin became the world's

neg: Hyperlipidemia cause atherosclerosis. Types Both conditions are treated with fibrate drugs, which act on the peroxisome proliferator-activated receptors (PPARs), specifically PPARα, to decrease free fatty acid production. Statin drugs, especially the synthetic statins (atorvastatin and rosuvastatin) can decrease LDL levels by increasing hepatic reuptake of LDL due to increased LDL-receptor expression. These unclassified forms are extremely rare: Acquired hyperlipidemias (also called secondary dyslipoproteinemias) often mimic primary forms of hyperlipidemia and can have similar consequences. They may result in increased risk of premature atherosclerosis or, when associated with marked hypertriglyceridemia, may lead to pancreatitis and other complications of the chylomicronemia syndrome. The

neg: Alzheimer's disease such as diet, cardiovascular risk, pharmaceutical products, or intellectual activities among others, and a population's likelihood of developing AD. Only further research, including clinical trials, will reveal whether these factors can help to prevent AD. Although cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes, and smoking, are associated with a higher risk of onset and course of AD, statins, which are cholesterol lowering drugs, have not been effective in preventing or improving the course of the disease. Long-term usage of non-steroidal anti-inflammatory drugs (NSAIDs) were thought in 2007 to be associated with a reduced likelihood of developing AD. Evidence also

neg: Pentostatin Pentostatin Pentostatin (or deoxycoformycin, trade name Nipent, manufactured by SuperGen) is an anticancer chemotherapeutic drug. It is classified as a purine analog, which is a type of antimetabolite. It mimics the nucleoside adenosine and thus inhibits the enzyme adenosine deaminase, interfering with the cell's ability to process DNA. Cancer cells generally divide more often than healthy cells; DNA is highly involved in cell division (mitosis) and drugs which target DNA-related processes are therefore more toxic to cancer cells than healthy cells. Pentostatin is used to treat hairy cell leukemia. It is given by intravenous infusion once every two weeks for

neg: Clarithromycin CYP3A4, involved in the metabolism of many other commonly prescribed drugs. Taking clarithromycin with other medications that are metabolized by CYP3A4 may lead to unexpected increases or decreases in drug levels. A few of the common interactions are listed below. Clarithromycin has been observed to have a dangerous interaction with colchicine as the result of inhibition of CYP3A4 metabolism and P-glycoprotein transport. Combining these two drugs may lead to fatal colchicine toxicity, particularly in patients with renal insufficiency. Taking clarithromycin concurrently with certain statins (a class of drugs used to reduce blood serum cholesterol levels) increases the risk of side

neg: Red yeast rice (血脂康). The test product was an ethanol extract of red yeast rice, with a monacolin K content of 11.6 mg/day. Key CCSPS results: In the treated group, risk of subsequent heart attacks was reduced by 45%, cardio deaths by 31%, and all-cause deaths by 33%. The CCSPS heart attack and cardiovascular death outcomes appear to be better than what has been reported for prescription statin drugs. A 2008 review pointed out that the cardioprotective effects of statins in Japanese populations occur at lower doses than are needed in Western populations, and theorized that the low amount of monacolins found in

neg: Organo anion transporter family use cytoplasmic glutamate as the exchanging anion. Among the well characterized substrates are numerous drugs including statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, antibiotics, antihistaminics, antihypertensives and anticancer drugs. Other substrates include luciferin, thyroid hormones and quinolones. The various paralogues in a mammal have differing but overlapping substrate specificities and tissue distributions as summarized by Hagenbuch and Meier. These authors also provide a phylogenetic tree of the mammalian members of the family, showing that they fall into five recognizable subfamilies, four of which exhibit deep branching sub-subfamilies. However, all sequences within a subfamily are >60% identical while those between subfamilies

neg: Steroid then be converted into other steroids, such as cholesterol and ergosterol. Two classes of drugs target the mevalonate pathway: statins (like rosuvastatin), which are used to reduce elevated cholesterol levels, and bisphosphonates (like zoledronate), which are used to treat a number of bone-degenerative diseases. Steroidogenesis is the biological process by which steroids are generated from cholesterol and changed into other steroids. The pathways of steroidogenesis differ among species. The major classes of steroid hormones, as noted above (with their prominent members and functions), are the Progestogen, Corticosteroids (corticoids), Androgens, and Estrogens. Human steroidogenesis of these classes occurs in a number

neg: Type genus Type genus In biological classification, especially zoology, the type genus is the genus which defines a biological family and the root of the family name. According to the International Code of Zoological Nomenclature, "The name-bearing type of a nominal family-group taxon is a nominal genus called the 'type genus'; the family-group name is based upon that of the type genus." Any family-group name must have a type genus (and any genus-group name must have a type species, but any species-group name may, but need not, have one or more type specimens). The type genus for a family-group name is also

neg: Discovery and development of statins different pharmacophore structure were found. This structure-based virtual screening procedure is considered promising for rational quest and optimization of potential novel HGMR inhibitors. Discovery and development of statins The discovery of HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitors, called statins, was a breakthrough in the prevention of hypercholesterolemia and related diseases. Hypercholesterolemia is considered to be one of the major risk factors for atherosclerosis which often leads to cardiovascular, cerebrovascular and peripheral vascular diseases. The statins inhibit cholesterol synthesis in the body and that leads to reduction in blood cholesterol levels, which is thought to reduce the risk of atherosclerosis and diseases caused

neg: Pitavastatin metabolism pathway of pitavastatin is glucuronidation. It is minimally metabolized by the CYP450 enzymes CYP2C9 and CYP2C8, but not by CYP3A4 (which is a common source of interactions in other statins). As a result, it is less likely to interact with drugs that are metabolized via CYP3A4, which might be important for elderly patients who need to take multiple medicines. Pitavastatin (previously known as itavastatin, itabavastin, nisvastatin, NK-104 or NKS-104) was discovered in Japan by Nissan Chemical Industries and developed further by Kowa Pharmaceuticals, Tokyo. Pitavastatin was approved for use in the United States by the FDA on 08/03/2009 under

neg: Discovery and development of statins Discovery and development of statins The discovery of HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitors, called statins, was a breakthrough in the prevention of hypercholesterolemia and related diseases. Hypercholesterolemia is considered to be one of the major risk factors for atherosclerosis which often leads to cardiovascular, cerebrovascular and peripheral vascular diseases. The statins inhibit cholesterol synthesis in the body and that leads to reduction in blood cholesterol levels, which is thought to reduce the risk of atherosclerosis and diseases caused by it. More than 100 years ago a German pathologist named Rudolf Virchow discovered that cholesterol was to be found in the artery

neg: Pitavastatin the trade name Livalo. Pitavastatin has been also approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in UK on 17 August 2010. Pitavastatin Pitavastatin (usually as a calcium salt) is a member of the blood cholesterol lowering medication class of statins, marketed in the United States under the trade name Livalo, and in European Union and Russia under the trade name Livazo. Like other statins, it is an inhibitor of HMG-CoA reductase, the enzyme that catalyses the first step of cholesterol synthesis. It has been available in Japan since 2003, and is being marketed in South Korea and

neg: Anarchist economics with mostly second-hand items—only everything is available at no cost. Whether it is a book, a piece of furniture, a garment or a household item, it is all freely given away, although some operate a one-in, one-out type policy (swap shops). The free store is a form of constructive direct action that provides a shopping alternative to a monetary framework, allowing people to exchange goods and services outside of a money-based economy. The anarchist 1960s countercultural group The Diggers opened free stores which simply gave away their stock, provided free food, distributed free drugs, gave away money, organized free music

neg: Proportional reporting ratio the same adverse event is reported for all drugs in the comparison group (relative to all adverse events for drugs in the comparison group). For example, suppose that nausea was reported 83 times for a given drug of interest, out of 1356 adverse events reported for the drug. Thus the proportion of adverse events of nausea for this drug is 83/1356 = 0.061. Suppose that we wish to compare the drug of interest to a class of drugs, for which nausea was reported as an adverse event 1489 times, out of 53789 total adverse events reported for drugs in the

neg: Human interactions with fungi Human interactions with fungi Human interactions with fungi include both beneficial uses, whether practical or symbolic, and harmful interactions such as when fungi damage crops, timber, or food. Yeasts have been used since ancient times to leaven bread and to ferment beer and wine. More recently, mould fungi have been exploited to create a wide range of industrial products, including enzymes and drugs. Medicines based on fungi include antibiotics, immunosuppressants, statins and many anti-cancer drugs. The yeast species "Saccharomyces cerevisiae" is an important model organism in cell biology. The fruiting bodies of some larger fungi are collected as edible mushrooms,

neg: Ixazomib Ixazomib Ixazomib (trade name Ninlaro) is a drug for the treatment of multiple myeloma, a type of white blood cell cancer, in combination with other drugs. It is taken by mouth in form of capsules. Common side effects include diarrhoea, constipation and low platelet count. Like the older bortezomib (which can only be given by injection), it acts as a proteasome inhibitor, has orphan drug status in the US and Europe, and is a boronic acid derivative. The drug was developed by Takeda. In the US, it is approved since November 2015, and in the EU since November 2016. Ixazomib

neg: Ixazomib be conducted. The approval indication is the same as in the US. , ixazomib is also in Phase III clinical trials for the treatment of AL amyloidosis and plasmacytoma of the bones, and in Phase I/II trials for various other conditions. Ixazomib Ixazomib (trade name Ninlaro) is a drug for the treatment of multiple myeloma, a type of white blood cell cancer, in combination with other drugs. It is taken by mouth in form of capsules. Common side effects include diarrhoea, constipation and low platelet count. Like the older bortezomib (which can only be given by injection), it acts as

neg: PON1 is also a major anti-atherosclerotic component of high-density lipoprotein (HDL). The PON1 gene is activated by PPAR-γ, which increases synthesis and release of paraoxonase 1 enzyme from the liver, reducing atherosclerosis. The "natural" substrates for PON1 appear to be lactones. However, PON1 has evolved to be a highly promiscuous enzyme capable of hydrolysing a wide variety of substrates such as lactones (including a number of important pharmaceutical agents such as statins), glucuronide drugs, thiolactones, arylesters, cyclic carbonates, organophosphorus pesticides and nerve gases such as sarin, soman and VX, oestrogen esters and lipid peroxides (oxidised lipids). PON1 in humans is encoded

neg: Drug reaction testing patients get the test before taking the medication. There are four possible categories for each marker: poor metabolizer, intermediate metabolizer, extensive metabolizer, or ultra-extensive metabolizer. Different testing companies may call these by different names. Extensive metabolizers (that is, people who are extensive metabolizers of a given type) are the most common, and are the type of people for which drugs are designed. Up to 7% of Caucasians are poor metabolizers of drugs metabolized by the CYP2D6 enzyme. People who cannot metabolize a drug will require a much lower dose than is recommended by the manufacturer, and those who metabolize it

neg: Triglyceride Niacin and omega-3 fatty acids as well as drugs from the statin class may be used in conjunction, with statins being the main medication for moderate hypertriglyceridemia when reduction of cardiovascular risk is required. Linseed oil and related oils are important components of useful products used in oil paints and related coatings. Linseed oil is rich in di- and tri-unsaturated fatty acid components, which tend to harden in the presence of oxygen. This heat-producing hardening process is peculiar to these so-called "drying oils". It is caused by a polymerization process that begins with oxygen molecules attacking the carbon backbone. Triglycerides

neg: Atorvastatin sand (less than 1 mm in size). The FDA received no reports of injury from the contamination. Ranbaxy also issued recalls of bottles of 10-milligram tablets in August 2012 and March 2014, due to concerns that the bottles might contain larger, 20-milligram tablets and thus cause potential dosing errors. Atorvastatin Atorvastatin, marketed under the trade name Lipitor among others, is a member of the medication class known as statins, which are used primarily as a lipid-lowering agent and for prevention of events associated with cardiovascular disease. Like all statins, atorvastatin works by inhibiting HMG-CoA reductase, an enzyme found in liver

neg: Fenofibrate approval for the use in high cholesterol treatment in combination with statins. Fenofibrate has been used since 1975 and is one of the most commonly prescribed fibrates. Fenofibrate is mainly used for primary hypercholesterolemia or mixed dyslipidemia. Fenofibrate appears to decrease the risk of cardiovascular disease and possibly diabetic retinopathy in those with diabetes mellitus, and firstly indicated for the reduction in the progression of diabetic retinopathy in patients with type 2 diabetes and existing diabetic retinopathy in Australia. It also appears to be helpful in decreasing amputations of the lower legs in this same group of people. Fenofibrate also

neg: Pitavastatin Pitavastatin Pitavastatin (usually as a calcium salt) is a member of the blood cholesterol lowering medication class of statins, marketed in the United States under the trade name Livalo, and in European Union and Russia under the trade name Livazo. Like other statins, it is an inhibitor of HMG-CoA reductase, the enzyme that catalyses the first step of cholesterol synthesis. It has been available in Japan since 2003, and is being marketed in South Korea and in India. It is expected that pitavastatin will be approved outside Southeast Asia as well. In the US, it received FDA approval in 2009.

neg: International Code of Zoological Nomenclature name. Any family-group name must have a type genus, any genus-group name must have a type species, and any species-group name can (not must) have one or more type specimens (holotype, lectotype, neotype, syntypes, or others), usually deposited in a museum collection. The type genus for a "family-group name" is simply the genus that provided the stem to which was added the ending "-idae" (for families). Example: The type species for a "genus-group name" is more complicated and follows exactly defined provisions in articles 67-69. Type species are very important, and no general zoological database has recorded the type species

neg: Barbiturate the Netherlands, the Opium Law classifies all barbiturates as List II drugs, with the exception of secobarbital, which is on List I. There is a small group of List II drugs for which doctors have to write the prescriptions according to the same, tougher guidelines as those for List I drugs (writing the prescription in full in letters, listing the patients name, and have to contain the name and initials, address, city and telephone number of the licensed prescriber issuing the prescriptions, as well as the name and initials, address and city of the person the prescription is issued to).

neg: Methanobrevibacter smithii is not inhibited by statins. In 2009, the largest human study concerning obesity and gut microbiota to date was conducted. Obesity disorders are the result of an imbalance and have serious consequences such as cardiovascular disease, type 2 diabetes, and colon cancer. The gut microbiota and environment contributes to the energy imbalance because of its involvement in energy intake, conversion and storage. Culture-independent methods have shown that high proportions of methanogens can comprise up to 10% of all anaerobes in the colons of healthy adults. The quantification average of "M. smithii" for the anorexic group was much greater than the

neg: Angina vasodilators, such as calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors along with HMG-CoA reductase inhibitors (statins), also has been shown to be effective in many women, and new drugs, such as Ranolazine and Ivabradine, have shown promise in the treatment of MVA. Other approaches include spinal cord stimulators, adenosine receptor blockade, and psychiatric intervention. Hospital admission for people with the following symptoms is recommended, as they may have unstable angina: pain at rest (which may occur at night), pain on minimal exertion, angina that seems to progress rapidly despite increasing medical treatment. All people with suspected angina should

neg: Catalyst (TV program) to a 60-minute format starting 2017. The new 2017 format utilises out-of-house talent who are experts in their respective fields, presenting 60-minute in depth documentaries. Documentaries aired have included virtual reality, driverless cars, dinosaurs, heart surgery, aliens and seaweed. The Catalyst team is composed of specialised science journalists, each with different specialisations and roles. A series of episodes ("Heart of the Matter, Parts 1 and 2") broadcast in October 2013 which questioned the link between saturated fat, cholesterol and heart disease, as well as the widespread use of anti-cholesterol drugs known as statins, have come under fire from doctors and

neg: Chemotherapy Chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents) as part of a standardized chemotherapy regimen. Chemotherapy may be given with a curative intent (which almost always involves combinations of drugs), or it may aim to prolong life or to reduce symptoms (palliative chemotherapy). Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called "medical oncology". The term "chemotherapy" has come to connote non-specific usage of intracellular poisons to inhibit mitosis, cell division.

neg: Variant angina of their coronary arteries. For the latter individuals, other, less fully investigated drugs may provide symptom relief. Statins, e.g. fluvastatin, while not evaluated in large-scale double-blind studies, are reportedly helpful in reducing variant angina attacks and should be considered in patients when calcium channel blockers and nitroglycerin fail to achieve good results. There is also interest in using rho-kinase inhibitors, such as fasudil (available in Japan and China but not the USA), and blocker of alpha-1 adrenergic receptors such as prazosin (which when activated cause vasodilation) but studies are needed to support their clinical utility in variant angina. Individuals with

neg: Lipoprotein lipase deficiency many of the patients. Lipid lowering drugs Lipid-lowering agents such as fibrates and omega-3-fatty acids can be used to lower TG levels in LPLD; however, those drugs are very often not effective enough to reach treatment goals in LPLD patients. Statins should be considered to lower elevated non-HDL-Cholesterol. Additional measures are avoidance of agents known to increase endogenous triglyceride levels, such as alcohol, estrogens, diuretics, isotretinoin, anidepressants (e.g. sertraline) and b-adrenergic blocking agents. Gene therapy In 2012, the European Commission approved alipogene tiparvovec (Glybera), a gene therapy for adults diagnosed with familial LPLD (confirmed by genetic testing) and suffering from

neg: Stroke equally important in secondary prevention. Even patients older than 80 years and those with isolated systolic hypertension benefit from antihypertensive therapy. The available evidence does not show large differences in stroke prevention between antihypertensive drugs —therefore, other factors such as protection against other forms of cardiovascular disease and cost should be considered. The routine use of beta-blockers following a stroke or TIA has not been shown to result in benefits. High cholesterol levels have been inconsistently associated with (ischemic) stroke. Statins have been shown to reduce the risk of stroke by about 15%. Since earlier meta-analyses of other lipid-lowering drugs

neg: Kalipada Pahan drugs. Later his lab has shown that statins may be beneficial in protecting neurons and improving locomotor activities in Parkinson's disease by suppressing the activation of p21/Ras. His lab is also famous for research on cinnamon where they have described that this commonly-used natural spice may be beneficial for different brain disorders including improving memory and learning of poor learners. Recently his lab has delineated a unique crosstalk between fat and memory in which the lipid-lowering transcription factor PPARalpha controls the formation of hippocampal memory via transcriptional regulation of CREB (Roy et al., 2013, Cell Reports 4: 724-737), suggesting a

neg: Discovery and development of statins because lipophilic statins passively and non-selectively diffuse into both hepatocyte and non-heptatocyte, while the hydrophilic statins rely largely on active transport into hepatocyte to exert their effects. High hepatoselectivity is thought to translate into reduced risk of adverse effects. It has been reported that the organic anion transporting polypeptide (OATP) is important for the hepatic uptake of hydrophilic statins such as rosuvastatin and pravastatin. OATP-C is expressed in liver tissue on the basolateral membrane of hepatocytes and is considered to be a potential contributor for the low IC for rosuvastatin in hepatocytes. Of the marketed statins, cerivastatin was the most

neg: Anti-diabetic medication disease of insulin resistance by cells. Type 2 diabetes mellitus is the most common type of diabetes. Treatments include (1) agents that increase the amount of insulin secreted by the pancreas, (2) agents that increase the sensitivity of target organs to insulin, and (3) agents that decrease the rate at which glucose is absorbed from the gastrointestinal tract. Several groups of drugs, mostly given by mouth, are effective in type 2, often in combination. The therapeutic combination in type 2 may include insulin, not necessarily because oral agents have failed completely, but in search of a desired combination of effects.

neg: Systematic name Systematic name A systematic name is a name given in a systematic way to one unique group, organism, object or chemical substance, out of a specific population or collection. Systematic names are usually part of a nomenclature. A semisystematic name or semitrivial name is a name that has at least one systematic part and at least one trivial part. Creating systematic names can be as simple as assigning a prefix or a number to each object (in which case they are a type of numbering scheme), or as complex as encoding the complete structure of the object in the name.

neg: Statin by at least 50%, and recommend statins for patients who will not benefit, based on populations whose observed risk is lower than predicted by the guidelines. The European Society of Cardiology and the European Atherosclerosis Society recommend the use of statins for primary prevention, depending on baseline estimated cardiovascular score and LDL thresholds. Statins are effective in decreasing mortality in people with pre-existing cardiovascular disease. They are also advocated for use in people at high risk of developing coronary heart disease. On average, statins can lower LDL cholesterol by 1.8 mmol/l (70 mg/dl), which translates into an estimated 60% decrease

neg: Raffi Khatchadourian human experiments. Khatchadourian unveiled the extent to which a vast assortment of different chemicals were being tested on, often unknowing, U.S. soldiers. The experiments were executed in an effort to create a viable form of psychochemical warfare. Ketchum told Khatchadourian about the experiments that took place at Edgewood. Soldiers were given drugs without any preparation or knowledge of what they were taking; they were studied, and then released without counselling or warning of potential effects. Ketchum also told Khatchadourian of an experimenter at Edgewood Arsenal by the name of Dr. Van Murray Sim. Sim believed that the type of psychochemical