«Rheumatoid Arthritis Case Study» - Free Essay Paper
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The Mechanism of Action of Prednisone
Prednisone is an agonist of the glucocorticoid receptor. Its first metabolism takes place in the liver where it is converted into prednisolone, its active form, by 11β-hydroxysteroid dehydrogenases. Prednisolone diffuses freely over the cell membranes and forms a chemical bond with high affinity to unique cytoplasmic receptors (Ruiz-Irastorza, Danza, & Khamashta, 2012). This chemical reaction can result to the following: reduction of the scar tissue or edema, suppression of humoral immune responses, interfering with the function of mediators of inflammatory response, and inhibition of leukocyte infiltration at the inflammation site (Ruiz-Irastorza, Danza, & Khamashta, 2012). The corticosteroids anti-inflammatory actions are believed to involve lipocortins (also referred to as annexin) proteins, which suppress the phospholipase A2. By stimulating the production of lipocortins proteins, prednisone is able to control the biosynthesis of leukotrienes, interleukins, and prostaglandins, which are strong mediators of inflammation (Ruiz-Irastorza, Danza, & Khamashta, 2012).
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Prednisone has the ability to cause the secretion of different elements of gastric juices. Suppressing the production of corticotropin can contribute to the inhibition of endogenous corticosteroids. Prednisone also has an ability to act as a stimulant to some minerals, in which loss of intracellular potassium and entry of sodium into cells is stimulated (Ruiz-Irastorza, Danza, & Khamashta, 2012). This is especially found in the kidney, whereby rapid ion exchange results in sodium hypertension and retention. Prednisone is eliminated through the urine as glucuronide and sulfate conjugates.
The Concern with Chronic Treatment with Glucocorticoids
Although glucocorticoids have been used for over 6 decades, there are still some controversies as for their usage (Saag, 2012). These controversies arise because of their perceived toxicity, especially when used for a long period. In spite of these concerns, glucocorticoids are considered beneficial when used in low dosages. However, some studies suggest that using low-dose glucocorticoids for a long period may lead to numerous, potentially serious side effects. This contributes to further concerns that the toxicity of glucocorticoids is both time and dose dependent. There are normally two types of dose-related side effects: 1) side effects that increase linearly with an increasing dose include sleep disturbance, parchment-like skin, leg edema, ecchymosis, Cushingoid phenotype, among others; 2) side effects that occur when glucocorticoid goes beyond a certain threshold include increase in blood pressure, listlessness and depression, glaucoma, among others (Saag, 2012). Taking a dose of 5mg/day or more can result to weight gain and epistaxis, while a very low dose is associated with cataract (Saag, 2012).
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Although less serious side effects, such as Cushingoid appearance and skin thinning are commonly of great concern to the patients, more debilitative and serious side effects, such as cataracts and vertebral fractures, could be initially asymptomatic or unrecognized (Saag, 2012). The side effects described above do not occur in everyone who uses glucocorticoids and those people who experience them are normally affected by just one or two side effects. There is no specific dose at which these adverse effects are sure to occur, but health providers’ start looking for them if an individual has taken 10mg/day for a year or more.
The Mechanism of Action of Methotrexate and Sulfasalazine
The mechanisms of action of methotrexate are not yet completely understood. Methotrexate diffuses into the cells through an active transport mechanism and when it is within the cell, it is changed into polyglutamate methotrexate. This conversion is done by folylpolyglutamyl synthase. Reversibly, polyglutamate methotrexate has an ability to suppress dihydrofolate reductase (Pagnoux & Goulet, 2009). It also has a capability of inhibiting other enzymes, particularly 5-aminoimidazole-4-carboxamide ribonucleotide transformylase and thymidylate synthase. Tetrahydrofolate (THF) is required in the synthesis of pyrimidine and purine precursors of RNA and DNA. THF is also vital for the methylation of RNA, DNA, as well as other proteins. Finally, the elimination of methotrexate from the cell is conducted by carriers of the ATP-binding cassette class (Pagnoux & Goulet, 2009). Methotrexate is also capable of inducing apoptosis or inhabitation proliferation of neoplastic cells and was thus first used by hematologists in the late 1940s (Pagnoux & Goulet, 2009).
The sulfasalazine mechanism of action, as well as its metabolites, such as the sulfapyridine (SP) and 5-aminosalicy acid (5-ASA) is not yet understood and its investigation is still going on. However, its mechanism of action is considered to be related to immunomodulatory or anti-inflammatory properties that have been discovered in in vitro and animal models, to its chemical attraction for connective tissue, or to the comparatively higher concentration it achieves in intestinal walls, liver, and serous fluids, as indicated in autoradiographic studies on animals (Peponis et al., 2010).
The Side Effects of Methotrexate and Sulfasalazine
There are a number of side effects associated with methotrexate treatment; luckily, the most severe adverse effects such as severe myelosuppression, interstitial pneumonitis, and hepatic cirrhosis are very rare. Other side effects associated with methotrexate include non-arteritic ischemic optic neuropathy, decreased reflex tear secretion, blepharitis, conjunctivitis, photophobia, blurred vision, ocular pain, and peri-orbital edema (Peponis et al., 2010). Gastrointestinal upset (diarrhea or nausea), oral ulcers, hair thinning, stomatitis, and mild alopecia are other side effects associated with this medication. These effects are connected to folic acid antagonism and can therefore be eliminated through folic acid supplementation. When folic acid is administered at a dose of 1mg/day, it does not affect the effectiveness of methotrexate and is normally taken together with methotrexate to minimize these side effects (Peponis et al., 2010). Some patients have also complained of having a feeling “wiped out,” fatigue and headache. These effects can be eliminated by increasing the folic acid dosage or using an activated folic acid form (Peponis et al., 2010).
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The side effects associated with taking sulfasalazine are relatively few and the drug is believed to be safe. Some of the side effects that have been associated with the sulfasalazine treatment include blurred near vision and peripheral facial nerve palsy (Peponis et al., 2010). Sulfasalazine may also cause allergic reactions and hypersensitivity such as Stevens-Johnson syndrome. Mild gastrointestinal complaints and mild cytopenias have also been reported, but these can be treated easily.