Methotrexate (MTX), is an antifolate drug that was first developed to treat certain types of cancer. The use in cancer therapy is at higher doses whereas its use in rheumatic diseases is at much lower doses. It was found that the addition of a maintenance therapy following remission comprising of 6 mercaptopurine daily along with methotrexate weekly resulted in higher chances of remission. As per the current ALL protocols, induction and consolidation therapy is followed by oral 6 MP/ methotrexate maintenance therapy is given until 2 to 3 years from diagnosis. The enzyme dihydrofolic acid reductase (DHFR), which acts by reducing dihydrofolates to tetrahydrofolates, is inhibited by methotrexate. The tetrahydrofolates that are formed by means of this enzyme are used in the synthesis of purine nucleotides and thymidylate as one - carbon carriers. Methotrexate, therefore, interrupts DNA synthesis, and interferes with its repair …show more content…
It is usually completely absorbed when administered parenterally.. About 50% of methotrexate in the serum is bound to plasma proteins. It can therefore be displaced by various compounds including sulfonamides, salicylates, tetracyclines, chloramphenicol, and phenytoin. Methotrexate, when given orally or parenterally, does not cross the blood-CSF barrier in therapeutic concentrations. However, intrathecal administration yields high CSF concentrations of the drug. Polyglutamated compounds are formed from methotrexate due to hepatic metabolism that may be also be reverted to form MTX by the enzymes hydrolases. The terminal half-life of methotrexate is nearly three to ten hours in those receiving doses less than 30 mg/m2 and can be 8 - 15 hours for those receiving higher doses of the drug. The primary route of elimination is renal and excretion and is dependent upon the dose as well as route of
The drug is primarily administered to a patient orally and the majority of the dosage is rapidly absorbed in the GI tract. Once ingested and absorbed, metoprolol quickly disperses throughout the body. Approximately 10% of metoprolol in the blood binds to serum albumin. Metabolism of the drug in the body occurs through the combination of alpha-hydroxylation, O-demethylation, and N-dealkylation via oxidative deamination.
However, the majority of known anti-cancer drugs target normal cells as well. Methotrexate, formerly known as amethopterin, is an antimetabolite used in the treatment of some forms of cancer (Shacter and Law, 1956). It inhibits the function of dihydrofolate reductase (DHFR) by tightly binding to the enzyme. Following this slow interaction between methotrexate and DHFR, an enzyme-NADPH-inhibitor complex is formed (Stone et al., 1984). Therein, DHFR is rendered unable to catalyze the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate (Anderson, 2017). Tetrahydrofolate is an important methyl group shuttle in the de novo synthesis of purine and pyrimidine nucleotides and some amino acids (Barbara and Hiroshi, 2002). Therefore, eliminating it from cells is a good therapeutic strategy against cancer cells, as it would limit the de novo synthesis of purines and pyrimidines (Lane and Fan, 2015). Inhibiting the function of DHFR by its competitive inhibitor methotrexate is one such good therapeutic strategy, as it would disable DHFR from converting dihydrofolate into tetrahydrofolate. However, some types of cancer cells had acquired some forms of resistance against methotrexate (Hans et al., 2011). Equally important, methotrexate should be administered in well established low doses, because it affects
Several of the officers of the company seem reluctant to contact the processor even though the math on the invoice is not correct. The invoice indicates that approximately $500,000 of the sales (2,000 items) are at 0.1% plus $.22. This would be the interchange price for a regulated debit card after add a markup of .05%. It also shows approximately $ 150,000 (300 items) at 1.48% plus $.05. When you do the math, you conclude that the total cost should be $3,175. You would expect this amount to carryforward to the front of the invoice, but it does not.
It’s important to visit a healthcare facility once an individual encounters signs of polycystic ovary syndrome and the physician may prescribe Metformin to treat PCOS.
Patients suffering from rheumatoid arthritis are advised by doctors to start treatment with disease-modifying antirheumatic drugs (DMARDs). DMARDs help relieve the symptoms as well as the progression from joint damage. A common DMARD used in relieving the symptoms and stopping the progression of joint damage is Methotrexate. “Although biologic agents were first established as combination therapy with DMARDs such as MTX, Gómez-Reino discusses data from clinical trials in which biologic monotherapy was used as an effective treatment for patients with RA”(Smolen & Keystone ,2012). DMARDs such as methotrexate is an effective treatment for treating the symptoms of Rheumatoid Arthritis. DMARDs are often prescribed along with nonsteroidal anti-inflammatory drugs (NSAIDs) to assist in reducing swelling and
The bioavailability of the carboxylate is estimated to be approximately 80%, and the time to maximum plasma concentration of the carboxylate is between 2.5 and 5 hours.
Diclofenac is 100% absorbed after oral administration compared to IV administration as measured by urine recovery. However, due to first-pass metabolism, only about 50% of the absorbed dose is systemically available .Food has no significant effect on the extent of diclofenac absorption. However, there is usually a delay in the onset of absorption of 1 to 4.5 hours and a reduction in peak plasma levels of < 20%. Diclofenac is primarily metabolized by CPY2C9. Diclofenac is eliminated through metabolism and subsequent urinary and biliary excretion of the glucuronide and the sulfate conjugates of the metabolites
Deferoxamine mesylate can be used for treating acute iron intoxication. Deferoxamine complexed with iron to form ferrioxamine and then prevented the iron from entering into further chemical reactions. The formed chelate is readily soluble in water and passes easily through the kidney [1].
Methotrexate is a competitive inhibiter of binding of dihydrofolic acid (FH2) to the enzyme dihydrofolate reductase (DHFR). METHOTREXATE is a structural analogue of folic acid which make it can easily bind to the same receptor. DHFR is responsible for reducing FH2 to folinic acid (FH4), the active intracellular metabolite. Thus, METHOTREXATE decreases the amount of intracellular FH4 available and affects the metabolic pathways within the cell that are FH4 dependent. These pathways include pyrimidine metabolism and purine, polyamine synthesis and amino
Metformin is widely used to treat type 2 diabetes who do not have severe nephritis, cardiovascular disease or liver disease. It is one of the best first line treatment for type 2 diabetes which was first marketed named as Glucophage. Metformin also used in the treatment of polycystic ovary syndrome and increasing the use day by day.
Before watching "Opiate Addiction: A new medication". I did hear about replacement therapy and like most people I thought it was a substitute for the actual drug. After watching the video I realized the importance of replacement therapy. Methadone doesn't just treat the withdrawal symptoms of opiate addiction, it treats the brain itself. Methadone corrects the chemical changes in the brain causes by the opiates.
Antionette, I really enjoyed reading your post as it was well written and you have some really good ideas. One of the most important things that you mentioned was that police officers must know the department’s expectations of them, especially that of personal conduct. This will make the supervisor’s job much easier as the officer will know what activities and actions will not be tolerated. The second most important idea was how important the public’s trust is. Look at Ferguson, Missouri, where trust had been lost for many years. The public did not trust the police, even when it was proven that they did no wrong. Not investigating civilian complaints against officers is the easiest way to lose that trust. I have found that many
Streptococcus aureus is a universally known gram-positive bacterium and is most commonly found in infections. It is also known to have an ability to evolve and adapt to antibiotics such as penicillin and methicillin. S. aureus was regularly treated with penicillin up until the point it obtained a resistance to penicillin around 1948. This occurrence caused the switch from penicillin to methicillin to treat infections with S. aureus. However, over time Streptococcus aureus gained and developed several strains that are resistant to methicillin around 1961. These strains are known as MRSAs, which is short for methicillin resistant Streptococcus aureus. (Robinson 2003) Although not everything about the methicillin resistance in S. aureus is known,
Methotrexate has as its principal mechanism of action the competitive inhibition of the enzyme folic acid reductase. Folic acid must be reduced to tetrahydrofolic acid by this enzyme in the process of DNA synthesis and cellular replication. Methotrexate
“Thin” a documentary about women facing their eating disorders. “Thin” focused on four particular women Polly, Shelley, Brittany, and Alisa. These women were all brave enough to realize they had a problem and wanted help with the exception of Brittany. Sometimes when I hear about women with eating disorders I can be unsympathetic. I just feel there are so many things in life to think about other than what people think of you. Then I had to realize media has a lot to do with the way our young women picture themselves. We all want to look like this superstar. They all see this fat, ugly person when they look in the mirror and I realized I do the same thing, if we admit it we’ve all done it. The only difference is I’ve