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Discovery And Development Of Gastrointestinal Lipase Inhibitors
Lipase inhibitors belong to a drug class that is used as an antiobesity agent. Their mode of action is to inhibit gastric and pancreatic lipases, enzymes that play an important role in the digestion of dietary fat. Lipase inhibitors are classified in the ATC-classification system as A08AB (peripherally acting antiobesity products). Numerous compounds have been either isolated from nature, semi-synthesized, or fully synthesized and then screened for their lipase inhibitory activity but the only lipase inhibitor on the market (October 2016) is orlistat (Xenical, Alli). Lipase inhibitors have also shown anticancer activity, by inhibiting fatty acid synthase. Discovery of lipase inhibitors and their development Pancreatic lipase inhibitor was originally discovered and isolated from fermented broth of the Streptomyces toxytricini bacterium in 1981 and named lipstatin. It is a selective and potent irreversible inhibitor of human gastric and pancreatic lipases. Tetrahydrolipstatin, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Orlistat
Orlistat, sold under the brand name Xenical among others, is a medication used to treat obesity. Its primary function is preventing the absorption of fats from the human diet by acting as a lipase inhibitor, thereby reducing caloric intake. It is intended for use in conjunction with a healthcare provider-supervised reduced-calorie diet. Orlistat is the saturated derivative of lipstatin, a potent natural inhibitor of pancreatic lipases isolated from the bacterium ''Streptomyces toxytricini''. However, due to its relative simplicity and stability, orlistat was chosen over lipstatin for development as an anti-obesity drug. The effectiveness of orlistat in promoting weight loss is definite but modest. Pooled data from clinical trials suggest that people given orlistat in addition to lifestyle modifications, such as diet and exercise, lose about more than those not taking the drug over the course of a year. Orlistat also modestly reduces blood pressure and appears to pre ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Lipstatin
Lipstatin is a potent, irreversible inhibitor of pancreatic lipase. It is a natural product that was first isolated from the actinobacterium ''Streptomyces toxytricini''. The popular antiobesity drug orlistat (trade names Xenical and alli) is a saturated derivative of lipstatin. Biosynthesis Lipstatin is composed of a 2-hexyl-3,5-dihydroxy-7,10-hexadecadienoic-β-lactone 22 carbon backbone from fatty acid synthesis pathway and an ''N''-formyl-L-leucine group ester linked to the 5-hydroxyl group of the back bone. The composts of the lipstatin are ultimately from linoleic acid, octanoic acid, and L-leucine. The 22 carbon β-lactone moiety is derived from Claisen condensation between 3-hydroxytetradeca-5,8-dienyl-CoA derived from linoleic acid and hexyl-malonyl-ACP derived from octanoic acid. Linoleic acid is first attached to CoA through some acyl-CoA synthetase homologue synthesized by lipstatin biosynthetic operons (''Lst'') and goes through two β-oxidation to hydroxytet ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Prothrombin Time
The prothrombin time (PT) – along with its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) – is an assay for evaluating the ''extrinsic'' pathway and common pathway of coagulation. This blood test is also called ''protime INR'' and ''PT/INR''. They are used to determine the clotting tendency of blood, in such things as the measure of warfarin dosage, liver damage, and vitamin K status. PT measures the following coagulation factors: I (fibrinogen), II (prothrombin), V (proaccelerin), VII (proconvertin), and X (Stuart–Prower factor). PT is often used in conjunction with the activated partial thromboplastin time (aPTT) which measures the ''intrinsic'' pathway and common pathway of coagulation. Laboratory measurement The reference range for prothrombin time depends on the analytical method used, but is usually around 12–13 seconds (results should always be interpreted using the reference range from the laboratory that perform ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Anticoagulants
Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where they help keep the bite area unclotted long enough for the animal to obtain some blood. As a class of medications, anticoagulants are used in therapy for thrombotic disorders. Oral anticoagulants (OACs) are taken by many people in pill or tablet form, and various intravenous anticoagulant dosage forms are used in hospitals. Some anticoagulants are used in medical equipment, such as sample tubes, blood transfusion bags, heart–lung machines, and dialysis equipment. One of the first anticoagulants, warfarin, was initially approved as a rodenticide. Anticoagulants are closely related to antiplatelet drugs and thrombolytic drugs by manipulating the various pathways of blood coagulation. Specifically, antiplatelet drugs inhibit platel ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Drug Interaction
Drug interactions occur when a drug's mechanism of action is disturbed by the concomitant administration of substances such as foods, beverages, or other drugs. The cause is often the inhibition of the specific receptors available to the drug, forcing the drug molecules to bind to other non-intended targets which results in an array of side-effects. The term selectivity describes a drug’s ability to target a single receptor, rendering a predictable physiological response. For example, the binding of acetylcholine to muscarinic tracheal smooth-muscle receptors (M3) results in smooth muscle contractions. When free receptors become occupied by agonists - drugs that bind and activate receptors - and antagonists - drugs that inhibit/ block activation - the opportunity for drugs to target their intended receptor decreases as most receptors are already occupied. Therefore, when the number of free receptors decreases, the drugs begin binding to other secondary receptors, cau ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Abdominal Pain
Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues. Common causes of pain in the abdomen include gastroenteritis and irritable bowel syndrome. About 15% of people have a more serious underlying condition such as appendicitis, leaking or ruptured abdominal aortic aneurysm, diverticulitis, or ectopic pregnancy. In a third of cases the exact cause is unclear. Given that a variety of diseases can cause some form of abdominal pain, a systematic approach to the examination of a person and the formulation of a differential diagnosis remains important. Differential diagnosis The most frequent reasons for abdominal pain are gastroenteritis (13%), irritable bowel syndrome (8%), urinary tract problems (5%), inflammation of the stomach (5%) and constipation (5%). In about 30% of cases, the cause is not determined. About 10% of cases have a more serious cause including gallbladder ( gallstones or biliary dyskin ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Steatorrhea
Steatorrhea (or steatorrhoea) is the presence of excess fat in feces. Stools may be bulky and difficult to flush, have a pale and oily appearance, and can be especially foul-smelling. An oily anal leakage or some level of fecal incontinence may occur. There is increased fat excretion, which can be measured by determining the fecal fat level. The definition of how much fecal fat constitutes steatorrhea has not been standardized. Causes Impaired digestion or absorption can result in fatty stools. Possible causes include exocrine pancreatic insufficiency, with poor digestion from lack of lipases, loss of bile salts, which reduces micelle formation, and small intestinal disease-producing malabsorption. Various other causes include certain medicines that block fat absorption or indigestible or excess oil/fat in diet. The absence of bile secretion can cause the feces to turn gray or pale. Bile is responsible for the brownish color of feces. Other features of fat malabsorption may ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin with loss of the normal stretchiness of the skin and irritable behaviour. This can progress to decreased urination, loss of skin color, a fast heart rate, and a decrease in responsiveness as it becomes more severe. Loose but non-watery stools in babies who are exclusively breastfed, however, are normal. The most common cause is an infection of the intestines due to either a virus, bacterium, or parasite—a condition also known as gastroenteritis. These infections are often acquired from food or water that has been contaminated by feces, or directly from another person who is infected. The three types of diarrhea are: short duration watery diarrhea, short duration bloody diarrhea, and persistent diarrhea (lasting more than two wee ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Adverse Effects
An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a " side effect", when judged to be secondary to a main or therapeutic effect. The term complication is similar to adverse effect, but the latter is typically used in pharmacological contexts, or when the negative effect is expected or common. If the negative effect results from an unsuitable or incorrect dosage or procedure, this is called a medical error and not an adverse effect. Adverse effects are sometimes referred to as " iatrogenic" because they are generated by a physician/treatment. Some adverse effects occur only when starting, increasing or discontinuing a treatment. Adverse effects can also be caused by placebo treatments (in which case the adverse effects are referred to as nocebo effects). Using a drug or other medical intervention which is contraindicated may increase the risk of adverse effects. Adverse effect ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dyslipidemia
Dyslipidemia is an abnormal amount of lipids (e.g. triglycerides, cholesterol and/or fat phospholipids) in the blood. Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular disease ( ASCVD). ASCVD includes coronary artery disease, cerebrovascular disease, and peripheral artery disease. Although dyslipidemia is a risk factor for ASCVD, abnormal levels don't mean that lipid lowering agents need to be started. Other factors, such as comorbid conditions and lifestyle in addition to dyslipidemia, is considered in a cardiovascular risk assessment. In developed countries, most dyslipidemias are hyperlipidemias; that is, an elevation of lipids in the blood. This is often due to diet and lifestyle. Prolonged elevation of insulin resistance can also lead to dyslipidemia. Likewise, increased levels of O-GlcNAc transferase (OGT) may cause dyslipidemia. Types Diagnosis Classification Physicians and basic researchers classify dyslipidemias in two distinct ways. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Food And Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food safety, tobacco products, caffeine products, dietary supplements, prescription and over-the-counter pharmaceutical drugs (medications), vaccines, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices (ERED), cosmetics, animal foods & feed and veterinary products. The FDA's primary focus is enforcement of the Federal Food, Drug, and Cosmetic Act (FD&C), but the agency also enforces other laws, notably Section 361 of the Public Health Service Act, as well as associated regulations. Much of this regulatory-enforcement work is not directly related to food or drugs, but involves such things as regulating lasers, cellular phones, and condoms, as well as control of disease in contexts v ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hoffmann-La Roche
F. Hoffmann-La Roche AG, commonly known as Roche, is a Swiss multinational healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX Swiss Exchange. The company headquarters are located in Basel. Roche is the fifth largest pharmaceutical company in the world by revenue, and the leading provider of cancer treatments globally. The company controls the American biotechnology company Genentech, which is a wholly owned affiliate, and the Japanese biotechnology company Chugai Pharmaceuticals, as well as the United States-based companies Ventana and Foundation Medicine. Roche's revenues during fiscal year 2020 were 58.32 billion Swiss francs. Descendants of the founding Hoffmann and Oeri families own slightly over half of the bearer shares with voting rights (a pool of family shareholders 45%, and Maja Oeri a further 5% apart), with Swiss pharma firm Novartis owning a fu ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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