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"Vitamin K" has also been used as a slang term for ketamine, an unrelated anaesthetic Vitamin K1 (phylloquinone). Both forms of the vitamin contain a functional naphthoquinone ring and an aliphatic side chain. Phylloquinone has a phytyl side chain.
Vitamin K2 (menaquinone). In menaquinone the side chain is composed of a varying number of isoprenoid residues. Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins, mostly required for blood coagulation but also involved in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives. This group of vitamins includes two natural vitamers: vitamin K1 and vitamin K2.
Vitamin K was identified in 1929 by Danish scientist Henrik Dam investigated the role of cholesterol by feeding chickens a cholesterol-depleted diet. After several weeks, the animals developed hemorrhages and started bleeding. These defects could not be restored by adding purified cholesterol to the diet. It appeared that together with the cholesterol a second compound had been extracted from the food, and this compound was called the coagulation vitamin. The new vitamin received the letter K because the initial discoveries were reported in a German journal, in which it was designated as Koagulationsvitamin. In contrast to MK4, MK7 is not produced by humans but is converted from phylloquinone in the intestines by gut bacteria. However, bacteria-derived menaquinones appear to contribute minimally to overall vitamin K status. MK4 and MK7 are both found in the United States in dietary supplements for bone health. The US FDA has not approved any form of vitamin K for the prevention or treatment of osteoporosis; however, MK4 has been shown to decrease fractures up to 87%. In the amount of 45 mg daily MK4 has been approved by the Ministry of Health in Japan since 1995 for the prevention and treatment of osteoporosis. MK4 has also been shown to prevent bone loss and/or fractures caused by corticosteroids (e.g., prednisone, dexamethasone, prednisolone), anorexia nervosa, cirrhosis of the liver, postmenopausal osteoporosis, disuse from stroke, Alzheimer s disease, Parkinson disease, primary biliary cirrhosis and leuprolide treatment (for prostate cancer). MK7 has never been shown in any clinical trials to reduce fractures and is not approved by any government for the prevention or treatment of any disease. However, in 19 February 2011, HSA (Singapore) has approved a Health Supplement (Fitness+ Natto Essence MK7) which contains Vitamin K2 (MK7) and Vitamin D3 in it's purpose in increasing bone mineral density.
K4. It is generally accepted that the naphthoquinone is the functional group. And in an animal model MK4 was shown to prevent arterial calcifications. Phylloquinone (also known as vitamin K1) invariably contains in its side chain four isoprenoid residues. These results are reinforced by human cohort studies. In this study vitamin K1 was also tested and shown to not prevent arterial calfications. in the elderly there is a reduction in vitamin K2 production. resulting in malabsorption of the molecule. Recent research results also demonstrate that the small intestine and large intestine (colon) seem to be inefficient at absorbing vitamins K. and vary in the aliphatic side chain attached at the 3-position (see figure 1). The modified residues are often (but not always) . where a majority of the subjects showed inadequate vitamins K amounts in the body. This was revealed by the presence of large amounts of incomplete gamma-carboxylated proteins in the blood. one of which is unsaturated. where n specifies the number of isoprenoids. vitamins K3. an indirect test for vitamins K deficiency. generally they are designated as MK-n. pointing to its potential role in cardiovascular disease prevention. however. which are used in many areas including the pet food industry (vitamin K3) and to inhibit fungal growth (vitamin K5). These differences are caused by the different lipophilicity of the various side chains. Substantial differences may be expected. and K5. Chemical structure All members of the vitamin K group of vitamins share a methylated naphthoquinone ring structure. Taking broad-spectrum antibiotics can reduce vitamin K production in the gut by nearly 74% in people compared to those not taking these antibiotics. with respect to intestinal absorption. and bio-availability. Physiology Vitamin K is involved in the carboxylation of certain glutamate residues in proteins to form gammacarboxyglutamate residues (abbreviated Gla-residues). Additionally. tissue distribution. so that the mechanism of action is similar for all K-vitamins. as seen in broad spectrum antibiotic use. Menaquinones have side chains composed of a variable number of unsaturated isoprenoid residues. and by the different food matrices in which they occur. Diets low in vitamin K also decrease the body's vitamin K concentration. There are three synthetic forms of vitamin K.Vitamin K absorption and dietary need Previous theory held that dietary deficiency is extremely rare unless the intestine (small bowel) was heavily damaged. The other at-risk group for deficiency were those subject to decreased production of K2 by normal flora. transport.
vitamin K is stored in the fat tissue of the human body. D.S. factors VII. In 2002 it was found that to get maximum carboxylation of osteocalcin. Blood clotting (Coagulation) studies in humans using 45 mg per day of vitamin K2 (as MK4) and even up to 135 mg/day (45 mg three times daily) of K2 (as MK4). Gla-residues are usually involved in binding calcium. X. Like other liposoluble vitamins (A. and transmembrane gcarboxyglutamyl proteins (TMGs) 3 and 4. Drug interactions . IX. Dietary Reference Intake (DRI) for an Adequate Intake (AI) of vitamin K for a 25-year old male is 120 micrograms/day. also called bone Gla-protein (BGP). there is no known toxicity associated with high doses of the phylloquinone (vitamin K1) or menaquinone (vitamin K2) forms of vitamin K and therefore no tolerable upper intake level (UL) has been set. Bone metabolism: osteocalcin.situated within specific protein domains called Gla domains. matrix gla protein (MGP). At this time 15 human proteins with Gla domains have been discovered. Toxicity Although allergic reaction from supplementation is possible. Recommended amounts The U. for children and adolescents 15 100 micrograms/day. and protein Z). In fact. for infants is 10 20 micrograms/day. protein S. is demonstrably toxic. The Adequate Intake (AI) for adult women is 90 micrograms/day. protein C. and periostin. E). hemolytic anemia. and cytotoxicity in liver cells. showed no increase in blood clot risk. one may have to take up to 1000 g of vitamin K1. and they play key roles in the regulation of three physiological processes: Blood coagulation: (prothrombin (factor II). However. the FDA has banned this synthetic form of the vitamin from over-the-counter supplements because large doses have been shown to cause allergic reactions. Even doses in rats as high as 250 mg/kg body weight did not alter the tendency for blood-clot formation to occur. Vascular biology: growth arrest-specific protein 6 (Gas6) unknown function: proline-rich g-carboxyglutamyl proteins (PRGPs) 1 and 2. a synthetic form of vitamin K. vitamin K3 (menadione). The Gla-residues are essential for the biological activity of all known Gla-proteins.
 Some vegetable oils. newborn infants are at an increased risk of deficiency. and bleeding of the gums or nose. Menaquinone-4 and menaquinone-7 (vitamin K2) are found in meat. cauliflower. Colonic bacteria synthesize a significant portion of humans' vitamin K needs.in order to tide them over until day 5-7 when their colon becomes colonized. anemia. swiss chard. contain vitamin K. the rest (mainly MK-7) are synthesized by bacteria during fermentation. Deficiency Main article: Vitamin K deficiency Average diets are usually not lacking in vitamin K and primary vitamin K deficiency is rare in healthy adults. As previously mentioned. They also reverse the tendency of these drugs to cause arterial calcification in the long term. MK4 is synthesized by animal tissues. those on stringent diets. It is believed that phylloquinone's tight binding to the thylakoid membranes in the chloroplasts is the reason behind the poor bioavailability of vitamin K in green plants. cooked spinach has a 5 percent bioavailability of phylloquinone. However when one adds fat to the spinach. By way of reference. . broccoli. and Brassica (e. some fruits such as avocado. For example. Sources Vitamin K1 is found chiefly in leafy green vegetables such as spinach. and natto. They could also have disorders such as coagulopathy. cabbage. barbiturates. alcoholics). Other populations with an increased prevalence of vitamin K deficiency include individuals who suffer from liver damage or disease (e. kiwifruit and grapes are also high in vitamin K. but at levels that would require relatively large calorific consumption to meet the USDA recommended levels. and those taking anticoagulants. bruising. the bioavailability increases to 13 percent due to the increased solubility of vitamin K in fat.this is one of the reasons why newborns often receive a vitamin K shot at birth. although the mechanism is still unknown. Other drugs that have been associated with vitamin K deficiency include salicylates.g. two tablespoons of parsley contain 153% of the recommended daily amount of vitamin K. people with cystic fibrosis. and brussels sprouts). There is no difference between the sexes as both males and females are affected equally. dairy. notably soybean.g. which work by interfering with the action of vitamin K. In natto 0% of vitamin K is from MK-4 and in cheese 2 7%. Groups that may suffer from secondary vitamin K deficiency include bulimics.Phylloquinone (K1) or menaquinone (K2) are capable of blocking the blood thinning action of anticoagulants like warfarin. Symptoms of deficiency include heavy menstrual bleeding in women. and cefamandole. inflammatory bowel diseases or those who have recently had abdominal surgeries. eggs. kale.
The carboxylation reaction will only proceed if the carboxylase enzyme is able to oxidize vitamin K hydroquinone to vitamin K epoxide at the same time. such that the carboxylation reaction catalyzed by the glutamyl carboxylase is inefficient. . These two enzymes comprise the so-called vitamin K cycle. IX. and the Factor X-targeting protein Z. Without Gla on the amino termini of these factors. This results in the production of clotting factors with inadequate Gla. (See the warfarin article. VII. the presence of the Gla-residues in these proteins turned out to be essential for functional activity.Osteoporosis and coronary heart disease are strongly associated with lower levels of K2 (menaquinone). or Gla-proteins At present. Biochemistry Function The function of vitamin K in the cell is to convert glutamate in proteins to gamma-carboxyglutamate (gla). the cell growth regulating growth arrest specific gene 6 protein (Gas6). As it is impossible to predict what dose of warfarin will give the desired degree of suppression of the clotting. the calcification inhibiting matrix gla protein (MGP). and the four transmembraneGla proteins (TMGPs) the function of which is at present unknown. they no longer bind stably to the blood vessel endothelium and cannot activate clotting to allow formation of a clot during tissue injury. Warfarin and other coumarin drugs block the action of the vitamin K epoxide reductase. This results in decreased concentrations of vitamin K and vitamin K hydroquinone in the tissues. the carboxylation and epoxidation reactions are said to be coupled reactions.) Gamma-carboxyglutamateproteins. Vitamin K epoxide is then re-converted to vitamin K by vitamin K epoxide reductase. and X. Another enzyme then oxidizes vitamin K hydroquinone to allow carboxylation of Glu to Gla. the following human Gla-containing proteins have been characterized to the level of primary structure: the blood coagulation factors II (prothrombin). Within the cell. warfarin treatment must be carefully monitored to avoid over-dosing. Gas6 can function as a growth factor that activates the Axl receptor tyrosine kinase and stimulates cell proliferation or prevents apoptosis in some cells. vitamin K undergoes electron reduction to a reduced form of vitamin K (called vitamin K hydroquinone) by the enzyme vitamin K epoxide reductase (or VKOR). Menaquinone is not inhibited by salicylates as happens with K1. the anticoagulant proteins C and S. In all cases in which their function was known. The bone Gla-protein osteocalcin. so menaquinone supplementation can alleviate the chronic vitamin K deficiency caused by long term aspirin use. One of the reasons humans are rarely deficient in vitamin K is that vitamin K is continually recycled in our cells. this enzyme is called the gammaglutamyl carboxylase or the vitamin K-dependent carboxylase.
a small molecule with an excess of electrons (also called an electron donor) such as lactate. and fish. Methods of assessment Prothrombin time test: Measures the time required for blood to clot Blood sample mixed with citric acid and put in a fibrometer. birds. but not vitamin K1 (phylloquinone). in some cases activation is accomplished by snake Gla-containing enzymes that bind to the endothelium of human blood vessels and catalyze the conversion of procoagulant clotting factors into activated ones. leading to unwanted and potentially deadly clotting. which is sufficiently toxic to kill an adult human.Gla-proteins are known to occur in a wide variety of vertebrates: mammals. Another interesting class of invertebrate Gla-containing proteins is synthesized by the fish-hunting snail Conusgeographus. in a process called anaerobic respiration. such as Escherichia coli found in the large intestine. reported no correlation between FFQ and plasma phylloquinone  Urinary -carboxyglutamic acid: Urinary Gla responds to changes in dietary vitamin K intake. In a study by Booth et al. Remarkably. menaquinone will transfer two electrons between two different small molecules. . Unfortunately insensitive to mild deficiency as the values do not change until the concentration of prothrombin in the blood has declined by at least 50 percent  Plasma Phylloquinone: Was found to be positively correlated with phylloquinone intake in elderly British women. The venom of a number of Australian snakes acts by activating the human blood clotting system. For example. or conotoxins. increases of phylloquinone intakes from 100 g to between 377 417 g for 5 days did not induce a significant change Response may be age-specific  Function in bacteria Many bacteria. can synthesize vitamin K2 (menaquinone). Delayed clot formation indicates a deficiency. but not men  However an article by Schurges et al. These snails produce a venom containing hundreds of neuro-active peptides. reptiles. Several of the conotoxins contain 2 5 Gla residues. Several days are required before any change can be observed. In these bacteria.
Vitamin K injection in newborns The blood clotting factors of newborn babies are roughly 30 to 60 percent that of adult values. the final oxidant is molecular oxygen (O2) . Controversy Controversy arose in the early 1990s regarding this practice when two studies were shown suggesting a relationship between parenteral administration of vitamin K and childhood cancer (14)[verification needed]. USA As a result of the occurrences of vitamin K deficiency bleeding. this may be due to the reduced synthesis of precursor proteins and the sterility of their guts. UK In the UK. Human milk contains between 1 and 4 micrograms/litre of vitamin K1. poor methods and small sample sizes led to the discrediting of these studies and a review of the evidence published in 2000 by Ross and Davies found no link between the two. It is estimated that there is a 0. except that the final electron acceptor is not molecular oxygen. the Committee on Nutrition of the American Academy of Pediatrics has recommended that 0. However. will pass two electrons to a menaquinone. ATP. Some of these reactions generate a cellular energy source. in a manner similar to eukaryotic cell aerobic respiration. while formula derived milk can contain up to 100 micrograms/litre in supplemented formulas. vitamin K is administered to newborns as either a single injection at birth or three orally administered doses given at birth and then over the baby's first month. with the help of an enzyme.5 to 1. The menaquinone.0 mg vitamin K1 be administered to all newborns shortly after birth. but say fumarate or nitrate (In aerobic respiration. will in turn transfer these 2 electrons to a suitable oxidant. Vitamin K2 concentrations in human milk appear to be much lower than those of vitamin K1. with the help of another enzyme.7 percent occurrence of vitamin K deficiency bleeding in the first week of the infant's life with a prevalence of 2-10 cases per 100.000 births.25 to 1. respectively.[verification needed] .formate. Adding two electrons to fumarate or nitrate will convert the molecule to succinate or nitrite + water. such fumarate or nitrate (also called an electron acceptor).) Escherichia coli can carry out aerobic respiration and menaquninone-mediated anaerobic respiration. or NADH. which accepts four electrons from an electron donor such as NADH to be converted to water. Premature babies have even lower levels of the vitamin and are at a higher risk from this deficiency.
Zambetti G & Stein G (1989) Structure of the rat osteocalcin gene and regulation of vitamin D-dependent expression. There is physiological and observational evidence that vitamin K plays a role in bone growth and the maintenance of bone density. osteoblast-to-osteocyte transition. ProcNatlAcadSci 86. Collart D. Data from the 1998 Nurses Health Study. Mackowiak S.Other studies have shown that vitamin K antagonists (usually a class of anticoagulants) lead to early calcification of the epiphysis and epiphysial line in mice and other animals. K takes part in the post translational modification as a co-factor in . 25-dihydroxy vitamin D. Despite heavy doses of . After being given 110 micrograms/day of vitamin K. Tucker K. Chen H. a large multicentre randomized placebo-controlled trial was performed to test the supplementation of vitamin K in post-menopausal women with osteopenia. but efforts to delay the onset of osteoporosis by vitamin K supplementation have proven ineffective. Stewart C. K1 intake (median K1 intake of 254 g/ day) has 35% lower risk of hip fracture than those in the lowest quartile. which is necessary for their function. menatetrenone (MK4) and manadione (Vit. Shalhoub V. K dependant proteins (VKDPs). indicated an inverse relationship between dietary vitamin K1 and the risk of hip fracture. Study of Atkins et al. Asiri R W. Subjects in the highest quartile of Vit. Lian and his group (Lian J. VKDPs have glutamate residues (Glu). causing seriously decreased bone growth. In addition to this. D works in tandem for the bone metabolism and development. Comparing with the daily recommended intake (DRI) of 90 and 120 g/ day.) is another study that showed the similar result. high intakes of vitamin D but low intakes of vitamin K were suggested to pose an increased risk of hip fracture. K1) promote in vitro mineralisaton by human primary osteoblasts.carboxylation of Vit. Biophysical studies have indicated that supplemental vitamin K promotes osteotrophic processes and slows osteoclastic processes via calcium bonding. et al. women who consumed lettuce one or more times per day had a significantly lower risk of hip fracture than women who consumed lettuce one or fewer times per week. This is due to defects in osteocalcin and matrix gla protein. Their primary function is to prevent overcalcification of the bone and cartilage. However. 1201 1208. an observational study. They found a region 600 nucleotides immediately upstream from the transcription start site that support a 10-fold stimulated transcription of the gene by 1. both the above intakes are higher than existing DRI indicating the need for the revision of DRI taking into consideration the role it plays in bone health. K and Vik. Vitamin D is reported to regulate the OC transcribtion by osteoblast thereby showing that Vit. and an anticatabolic phenotype by -carboxylation-dependent and independent mechanisms.Vitamin K and bone health The role vitamin K plays in bone metabolism triggered a new thinking in its use as a therapeutic agent in diseases related with bone like osteoporosis. C1358 C1367) revealed that phylloquinone (Vitamin K1). Firmingham Heart Study (Booth SL. Katie JW. (2009) Vitamin K promotes mineralization. Am J ClinNutr 71. Am J Physiol Cell Physiol 297. (2000) Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women. Puchacz E. 1143 1147) discovered two nucleotide substitution regions which they named "osteocalcin box" in the rat and human osteocalcin genes. Vitamin K is important in the process of carboxylating glutamic acid (Glu) in these proteins to gamma-carboxyglutamic acid (Gla).(Gerald JA. et al. Vit.
to treat rosacea and to aid in the fading of hyperpigmentation and dark under-eye circles. Vitamin K used topically Vitamin K may be applied topically. MK4 in the dose of 45 mg daily is recognized as a treatment for osteoporosis. Vitamin K as antidote for poisoning by 4-hydroxcoumarin drugs . In the amount of 45 mg daily MK4 has been approved by the Ministry of Health in Japan since 1995 for the prevention and treatment of osteoporosis. disuse from stroke..vitamin K1.g. Vitamin K and Alzheimer's disease Research into the antioxidant properties of vitamin K indicates that the concentration of vitamin K is lower in the circulation of carriers of the APOE4 gene. dexamethasone. cirrhosis of the liver. In Japan. Parkinson disease. no differences were found in bone density between the supplemented and placebo groups. A German study performed on men with prostate cancer found a significant inverse relationship between vitamin K2 consumption and advanced prostate cancer. Vitamin K and cancer While researchers in Japan were studying the role of vitamin K2 in the prevention of bone loss in females with liver disease.. stop and reverse bone loss. It has been hypothesized that vitamin K may reduce neuronal damage and that supplementation may hold benefits to treating Alzheimer's disease. postmenopausal osteoporosis. typically as a 5% cream. This two year study which involved 21 women with viral liver cirrhosis found that women in the supplement group were 90 percent less likely to develop liver cancer. In studies MK4. prednisolone). Alzheimer s disease. they discovered another possible effect of this phytonutrient. MK4 has been shown to decrease fractures up to 87%. primary biliary cirrhosis and leuprolide treatment (for prostate cancer). although more research is necessary in this area. broken capillaries (spider veins). In contrast. but not MK7 or vitamin K1 prevented bone loss and/or fractures caused by corticosteroids (e. prednisone. to diminish postoperative bruising from cosmetic surgery and injections. anorexia nervosa. MK4 has been shown in numerous studies to reduce fracture risk. and recent studies have shown its ability to inhibit nerve cell death due to oxidative stress.
or Gla. It was shown that while warfarin-treated cows had a form of prothrombin that contained 10 glutamate amino acid residues near the amino terminus of this protein. afterwards (in the case of the more potent 4-hydoxycoumarins used as rodenticides). the animals developed hemorrhages and started bleeding. Treatment usually consists of repeated intravenous doses of vitamin K. If caught early. the normal (untreated) cows contained 10 unusual residues that were chemically identified as gamma-carboxyglutamate. and also anticoagulantmechanism poisons such as bromadiolone. Danish scientist Henrik Dam investigated the role of cholesterol by feeding chickens a cholesterol-depleted diet. even when great amounts of the drug or poison are ingested. University of Iowa Department of Pathology (Emory Warner. The extent to which blood coagulation was restored by the diet was taken as a measure for its vitamin K content. . History of discovery In 1929.. when three laboratories (Stenflo et al. prognosis is good. Dam and Doisy shared the 1943 Nobel Prize for medicine for their work on vitamin K (K1 and K2) published in 1939. and this compound was called the coagulation vitamin. Kenneth Brinkhous. 4hydroxycoumarin drugs possess anticoagulatory and rodenticidal properties because they inhibit vitamin K-dependent synthesis of some clotting factors by the liver. Nelsestuen et al.) isolated the vitamin K-dependent coagulation factor prothrombin (Factor II) from cows that received a high dose of a vitamin K antagonist. After several weeks. Albert Snell. and the Mayo Clinic (Hugh Butt. The first published report of successful treatment with vitamin K of life-threatening hemorrhage in a jaundiced patient with prothrombin deficiency was made in 1938 by Smith. Death is usually a result of internal hemorrhage. The precise function of vitamin K was not discovered until 1974. and Arnold Osterberg). It appeared that together with the cholesterol a second compound had been extracted from the food. though possibly up to 2 months. warfarin. These defects could not be restored by adding purified cholesterol to the diet. Warner. in which it was designated as Koagulationsvitamin. followed by doses in pill form for a period of at least two weeks. University of Copenhagen (Dam and Johannes Glavind). which are commonly found in rodenticides. and Brinkhous. For several decades the vitamin K-deficient chick model was the only method of quantifying vitamin K in various foods: the chicks were made vitamin K-deficient and subsequently fed with known amounts of vitamin K-containing food.. Several laboratories synthesized the compound(s) in 1939. Edward Adelbert Doisy of Saint Louis University did much of the research that led to the discovery of the structure and chemical nature of vitamin K. and Harry Pratt Smith). The new vitamin received the letter K because the initial discoveries were reported in a German journal. These include the pharmaceutical warfarin. The extra carboxyl group in Gla made clear that vitamin K plays a role in a carboxylation reaction during which Glu is converted into Gla. Three groups of physicians independently found this: Biochemical Institute. and Magnusson et al.Vitamin K is a true antidote for poisoning by 4-hydroxycoumarin anticoagulant drugs (sometimes loosely referred to as coumarins).
whereas glimepiride does not suppress this counter-regulatory reaction. Glibenclamide also interferes with the normal homeostatic suppression of insulin secretion in reaction to hypoglycemia. Main article: Sulfonylurea GI disturbance. Furthermore. Mechanism of action Main article: Sulfonylurea Like all sulfonylureas. glibenclamide diminishes the glucagon secretion in reaction to hypoglycemia. glimepiride acts as a secretagogue. with no interference of meals. rarely thrombocytopenia . Glimepiride Glimepiride is a medium-to-long acting sulfonylurea anti-diabetic drug. Glibenclamide (glyburide) is associated with an incidence of hypoglycemia of up to 20 30%. compared to 2% to 4% with glimepiride. It is marketed as Amaryl by Sanofi-Aventis and GLIMY by Dr. leukopenia. and distributed throughout the body. It lowers blood sugar by stimulating the release of insulin by pancreatic beta cells and by inducing increased activity of intracellular insulin receptors. and sometimes classified as second-generation. Not all secondary sufonylureas have the same risks of hypoglycemia. the remaining being excreted in the feces.5% and it is metabolized by oxidative biotransformation and 60% is excreted in the urine. hemolytic anemia.Reddy's Labs. Glimepiride is the first third-generation sulfonylurea. whereas glimepiride does not have this property. In the initial weeks of treatment. Significant absorption of glimepiride was seen within 1 hour. It is sometimes classified as third-generation. the risk of hypoglycemia may be increased. occasionally allergic reactions occur.The biochemistry of how vitamin K is used to convert Glu to Gla has been elucidated over the past thirty years in academic laboratories throughout the world. Pharmacokinetics With glimepiride GI absorption is complete. Interactions . and is very potent. bound to the plasma protein to an extent of 99.
Chloramphenicol.With NSAIDs like Salicylates. phenytoin tend to produce hyperglycemia. coumadin and probencid may potentiate the hypoglycemic action of glimepiride. phothiazides. Insulin Sensitizers Biguanides Metformin# Buformin TZDs (PPAR) Pioglitazone Rivoglitazone Dual PPAR agonist Aleglitazar Muraglitazar§ Tesaglitazar§ Rosiglitazone Troglitazone Phenformin Secretagogues K+ ATP Sulfonylureas 1st generation: Acetohexamide Carbutamide Chlorpropamide Tolbutamide Tolazamide 2nd generation: Glibenclamide (Glyburide)# Glipizide Gliquidone Glyclopyramide Gliclazide Meglitinides/"glinides" Nateglinide Repaglinide Mitiglinide GLP-1 analogs Exenatide Liraglutide Taspoglutide DPP-4 inhibitors Alogliptin Linagliptin Saxagliptin Sitagliptin Vildagliptin Albiglutide Lixisenatide Glimepiride Analogs/other insulins . oral contraceptives. other diuretic. thyroid products. Sulphonamides. Thiazides.
Contents [hide] 1 Indication 1. Withdrawn from market. and Temax (Wockhardt).1 Administration 2 Contraindications 3 Side effects 4 Mode of action 5 Clinical trials 5. Clinical trials: Phase III.1 ONTARGET 5.fast acting (Insulin lispro Insulin aspart Insulin glulisine) short acting (Regular insulin) long acting (Insulin glargine Insulin detemir NPH insulin) ultralong acting (Insulin degludec ) Inhalable Insulin Exubera Other Alpha-glucosidase inhibitors Acarbose Miglitol Voglibose Amylin analog Pramlintide SGLT2 inhibitors Canagliflozin Other Benfluorex Tolrestat Dapagliflozin Remogliflozin§ Sergliflozin§ #WHO-EM. Targit (Pfizer India). §Never to phase III Telmisartan Telmisartan (INN) ( /t lm s rt n/) is an angiotensin II receptor antagonist (angiotensin receptor blocker.2 TRANSCEND . ARB) used in the management of hypertension. It is marketed under the trade names Micardis (BoehringerIngelheim).
with a binding affinity 3000 times greater for AT1 than AT2.5. tongue. and allergic reactions. In addition to blocking the RAs. and neonatal deaths. Side effects Side effects are similar to other angiotensin II receptor antagonists and include tachycardia and bradycardia (fast or slow heartbeat).). . Contraindications Telmisartan is contraindicated during pregnancy. lips. It is believed that telmisartan s dual mode of action may provide protective benefits against the vascular and renal damage caused by diabetes and cardiovascular disease (CVD). Administration The usually effective dose telmisartan is (20 )40 80 mg once daily. telmisartan dose can be increased to a maximum of 80 mg once daily. stillbirths. In cases where the target blood pressure is not achieved. Mode of action Telmisartan is an angiotensin II receptor blocker that shows high affinity for the angiotensin II receptor type 1 (AT1). telmisartan can cause birth defects.3 PRoFESS 6 See also 7 References Indication Telmisartan is indicated in the treatment of essential hypertension. telmisartan acts as a selective modulator of peroxisome proliferatoractivated receptor gamma (PPAR. the latter leading to breathing problems). It should not be taken by breastfeeding women since it is not known whether the drug passes into the breast milk. a central regulator of insulin and glucose metabolism. edema (swelling of arms. or throat. It has the longest half-life of any ARB (24 hours) and the largest volume of distribution. hypotension (low blood pressure). Like other drugs affecting the renin-angiotensin system (RAS). Some patients may already benefit at a daily dose of 20 mg. legs.
" PRoFESS PRoFESS (Prevention Regimen For Effectively Avoiding Second Strokes) investigated therapy with telmisartan initiated soon after an ischemic stroke and continued for 2. The study showed that telmisartan was as effective as ramipril but with lower rates of cough and angioedema which led to fewer discontinuations. telmisartan was shown to be better tolerated and associated with higher treatment compliance than ramipril. myocardial infarction.620 patients from 733 centres in 41 countries were randomised for 5. in high CV risk patients. patients who could not tolerate ACE inhibitors were randomly assigned to receive either telmisartan or placebo as part of the TRANSCEND (Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (CVD)) study. in a patient population selected to tolerate ACE inhibitors. An accompanying editorial comments: "Overall. stroke or hospilization for heart failure. Moreover. TRANSCEND As part of the ONTARGET study. TRANSCEND's results challenge the non-inferiority shown in ONTARGET and suggest no more than a modest effect. The combination group experienced similar efficacy but with increased risk of hypotensive symptoms. This treatment did not significantly lower the rate of recurrent stroke.5 years. 25. or diabetes.5 years of treatment of either telmisartan. other than heart failure. the ACE inhibitor ramipril or a combination of the two.ONTARGET The ONTARGET Trial Programme (The Ongoing Telmisartan Alone and in combination with RamiprilGlobal Endpoint Trial) was one of the largest ARB clinical study programmes ever undertaken. if any at all. major cardiovascular events. . are incomplete. The study aimed to investigate the role of telmisartan in cardiovascular (CV) protection through the primary composite outcome of death from CV causes. data supporting use of angiotensin-receptor blockers to prevent vascular events in various cardiovascular groups.
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