History Of Non Steroidal Anti Inflammatory Biology Essay
Non steroidal Anti Inflammatory (NSAID’s), are a family of drugs which provide a sense of analgesia and/or anti inflammatory properties. NSAIDs are usually indicated for the treatment of acute or chronic conditions where pain and inflammation are present. Meloxicam (4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1, 2-benzothiazine-3-carboxamide-1, 1-dioxide.) is a derivate of oxicam, which are substances which bind closely to the plasma proteins. There are enolic acid groups of NSAID’s, the key factor is that they are weak acids, extremely weaker than, say, aspirin or ibuprofen. This means they give less gastric problems( decreases Disturbance of gastric mucosa leads to acid secretion, which prevents Acids contacting stomach nerve endings). Meloxicam was approved for use in April 2000.
Meloxicam is used to relieve pain, tenderness, swelling, and stiffness caused by osteoarthritis (a common condition that causes pain and inflammation within a joint.) and rheumatoid arthritis (swelling of the lining of the joints). Meloxicam is also used to relieve the pain, tenderness, swelling, and stiffness caused by juvenile rheumatoid arthritis in children 2 years of age and older. Meloxicam can also be used to relief people suffering from osteoarthritis usually at low doses but vary due to prescriber’s discrepancy.
Meloxicam is primarily ingested orally with either 7.5mg or 15mg Tablets daily. Once ingested, meloxicam is evenly distributed throughout the body via the blood stream limiting movement into the brain : by means of brain-blood barrier(BBB). A physiological mechanism that alters the permeability of brain capillaries so that some substances, such as certain drugs, are prevented from entering brain tissue, while other substances are allowed to enter freely as it is ingested orally, the drug takes longer to start to work as it is delocalised and not specific to its target. Meloxicam act primarily to reduce the biosynthesis of prostaglandins (PG) by inhibiting cyclooxygenase (COX), COX converts arachidonic acid (AA,)to prostaglandin H2 (PGH2), the precursor of the series-2 prostanoids.
Prostaglandins are unsaturated carboxylic acids, consisting of a 20 carbon skeleton that also contains a five member ring. Prostaglandins, are like hormones in that they act as chemical messengers, but do not move to other sites, but work right within the cells where they are synthesized. Prostaglandins are produced by the body in response to injury and certain diseases and conditions, and cause pain, swelling and inflammation. Meloxicam blocks the production of these prostaglandins and is therefore effective at reducing inflammation and pain.
Initially the meloxicam attaches to specific receptors in the phospholipid bilayer due to its selective permeability properties. This arrangement of phospholipids in bilayer is used to describe the cell membranes of many animal and plant cells. The two layers of phospholipids are arranged in a way that their hydrophobic tails are projecting to the interior whereas their hydrophilic heads are projecting the exterior. Usually, pain receptors(Nociceptor) in the hemispheres of the brain are stimulated, producing a mediator substance that is synthesised in the endoplasmic reticulum of the membrane : namely arachidonic acid. This intermediate fatty acid promotes the activation of prostaglandin synthetase(cyclo-oxygenase) an enzyme which propagates the production of the prostaglandins. As meloxicam interferes with the catalysed reactions leading to the synthesis of prostaglandin, it inhibits any further reaction(s) stimulating pain or inflammation leading to a sense of analgesia. Another affect of meloxicam is that it reduces the production of thromboxane which promotes platelet aggregation.
Like with an drug that are misused, side affects can occur. This effects can seem to amplify its desired effect or cause adverse effects. As was mentioned above, meloxicam is in the family of NSAID’s which are probably the most common family of analgises/ anti inflammatory drugs used in the developed world. In the UK meloxicam is prescribed, under the NHS, for patients suffering from pain and/ or inflammation. This course is usually short term due to the mild nature of the drug.. these patients are show not to aquire any unwanted side effects as the course is very short and the dosage may be insignificant to cause any sort of problem. Short courses are usually more suited to young children leading to young adults who have an acute problem e.g broken bone or an asthma attack.
However, patients whom have course of meloxicam or any other similar NSAID over a longer period of time are more susceptible due to the chronic nature of their imparement. Other factors such as gender, alcohol use, smoking and use of corticosteroids can also intertwine with the effects of NSAID. This patients tend to be over the age of 60. This means of treatment is only used when patients are more prone to heart attacks, strokes or heart failure and all other alternatives have been exhausted. The reason for this precaution approach is that meloxicam can have some adverse effects. Over use can result in two main problems; gastrointestinal (GI) and renal. GI refers to all the digestive organs, tissues and vessels that lead from the mouth to the anus. WHO (worldwide hearth organisation) estimated that over 60million people suffered GI induced problems as a result of use of NSAID including meloxicam. (known as NSAID-induced gastropathy). Gastropathy may refer to any number of medical conditions or diseases that affect the stomach. NSAID can cause peptic ulcerations and bleeding ; this may manifest as dyspepsia, iron deficiency anaemia, haematesmesis and melaena or ulcer perforation. A peptic ulcer is a sore on the lining of the stomach or duodenum—the beginning of the small intestine. As meloxicam inbihits COX1 and COX2 from catalysing their respected reactions it therefore haults the production of prostaglandins which protect the lining of the stomach from stomach acid and also helps prevent bleeding thus allowing peptic ulcers to occur.
Renal refers to anything related to the kidney. Prostaglandins are involved in the maintenance of renal blood flow and havr additional effects on the renal tubule that promotes natriuresis( process of excretion of sodium in the urine). Meloxicam can produce a reversible decline in renal function, with a rise in serum creatinine, salt and water retention leading to oedema( is the medical term for fluid retention in the body). Prostaglandins are also used in the kidney as a vascodilator of the afferent arteriole allowing for suffieicent blood flow thorugh the glomerulus and filtration through the glomerulus. However, as NSAIDs prevent prostaglandin production a decline in glomerular hydraulic pressure, the major driving force for glomerular filtration, can be seen leading to acute renal failure.
As with many pharmaceutical drugs, they all belong to a family of similar chemical and/or physical properties. Meloxicam as mentioned previous belongs to NSAID’s. NSAIDs differ in their duration of action, potency and the way in which they are eliminated from the body. Another important difference is their range of side effects : namely stomach alcers and promote bleeding. Meloxicam is sub grouped as part of enolic acid (oxicam) along with droxicam, peroxicam and isoxicam. All three are predominantly used as pain relief from acute illnesses like oesteoarthiritis or any inflammatory diseases. Most oxicams are unselective inhibitors of COX 1 and 2, unlike meloxicam, which has a slight preference to COX-2. This means that that unlike the rest meloxicam targets pain and inflammation primarily.
Asprin is one of the most commonly used non steroid anti inflammatory. If differs from meloxicam in a range of way. It inhibits the same Cyclooxygenase enzymes as meloxicam but I does so in an irreversible way by covalently modifying the enzyme. This doesn’t denature all enzymes just specifically changes that particular one. Another difference between the two is the routes of administrations. Meloxicam can only be taken orally whereas asprin can be taken orally, rectal, lysine acetylsalicylate(soluble form) or intravenously or intramuscularly. Both are similar due to their primarily uses however patients are strongly discouraged from taking the both at the same time. This is due to the fact one may contain an inactive ingredient which may cause effects when used coinciding with the other.