Non Steroidal Anti Inflammatory Drugs (NSAID): Effects

Non Steroidal Anti Inflammatory Drugs (NSAID): Effects Non steroidal anti inflammatory drugs or NSAIDs are inhibitors of prostaglandin, they have several key therapeutic effects, anti-inflammatory, antipyretic (reduces fevers) and analgesic. NSAIDs prevent the synthesis of prostaglandins; theses are made from the enzyme cyclo-oxygenase (COX) which supports inflammation, pain and fever, there are two cyclo-oxgenase COX-1 and COX-2. NSAIDs block the enzyme COX thus reducing the amount of prostaglandins and therefore reducing inflammation, pain and fevers. The main mechanism of action of NSAIDs is the inhibition of enzyme cyclo-oxygenase (COX). COX converts the fatty acid arachidonic acid into endoperoxide, prostaglandins and thromoxanes. The prostanoids have many physiological functions such as protecting the gastrointestinal tract, renal, homeostasis responses, platelet aggregation, contraction of uterine smooth muscle etc. There are two isoforms of COX, COX-1 and COX-2. COX-1 produces prostaglandin that support platelets and protect the stomach therefore has the most adverse side effects. COX-2 is inducible and found is inflammatory conditions and some types of carcinoma. Some drugs only inhibit COX-2 which reduces adverse effects that are associated with COX-1, such as the irritation of the stomach lining. Prostaglandins have numerous tasks to play as mediators of inflammation. They enhance the action of histamine and other natural compounds causing vasodilatation and increasing vascular permeability to fluids. These two factors re sult in the symptoms of inflammation. As well prostaglandins they relay pain messages to the brain. This journal article supports my essay on NSAIDs  [i]  Salicylic acid and salicylates, obtained from natural sources, have long been used as medicaments. Salicylic acid was chemically synthesized in 1860 and was used as an antiseptic, an antipyretic, and an antirheumatic. Twenty-five years ago, it was proposed that the mechanism of action of NSAIDs was through their inhibition of prostaglandin biosynthesis. Since then, there has been general acceptance of the concept that these drugs work by inhibition of the enzyme cyclo-oxygenase (COX), which we now know to have at least two distinct isoforms: the constitutive isoform, COX-1, and the inducible isoform, COX-2. COX-1 has clear physiologic functions. Its activation leads, for instance, to the production of prostacyclin, which when released by the endothelium is antithrombogenic and when released by the gastric mucosa is cytoprotective. COX-2, discovered 6 years ago, is induced by inflammatory stimuli and cytokines in migratory and other cells. It is therefore attractive to suggest that the anti-inflammatory actions of NSAIDs are due to inhibition of COX-2, whereas the unwanted side-effects, such as irritation of the stomach lining, are due to inhibition of COX-1. Drugs that have the highest COX-2 activity and a more favourable COX-2: COX-1 activity ratio will have a potent anti-inflammatory activity with fewer side-effects than drugs with a less favourable COX-2: COX-1 activity ratio. The identification of selective inhibitors of COX-2 will therefore lead to advances in therapy. NSAIDs are highly lipophilic substances, adsorption occurs through the gastrointestinal tract, as NSAIDs are weak acids they are less ionised in the gastric juices and therefore are absorbed by the mechanism of ionic or diffusion tapping. Most NSAIDs are given as oral tablets or capsules; others are given by injection to avoid gastric irritation. The main use of anti-inflammatory drugs is in the treatment of pain resulting from rheumatoid arthritis and osteoarthritis. Rheumatoid arthritis is an inflammatory condition of connective tissue especially within the joint capsule; it may be described as an autoimmune disease, whereby the bodys own immune system starts to destroy the synovial membrane. This may lead a complete destruction of the joint. Osteoarthritis is due to a mechanical damage to the joint which leads to degeneration of the articular cartilage the hip joint is commonly affected. Prostaglandins are found in the hypothalamus are involved in raising the temperature of the body during infection, therefore NSAIDs are useful in inhibiting prostaglandins and reducing body temperature, this is called antipyretic . Most prostaglandin inhibitors are acidic drugs that can directly irritate the gastric mucosa. Prostaglandins in the stomach lead to a decrease in gastric secretions; therefore, inhibiting the synthesis of prosta glandins leads to an increase in sections which may lead to ulcers. Aspirin is an irreversible inhibitor of COX-1 but has adverse side an effect, most side effects of NSAIDs is related to their action on the gastrointestinal tract. In the stomach prostaglandins are normally involved in the protection of the gastric mucosa (lining of the stomach) against the corrosive actions of the gastric acid; prevention of prostaglandin synthesis by NSAIDs therefore remove this protection and make the stomach open to irritation and ulceration. NSAIDs themselves are irritant chemicals which have a direct effect on the gastric mucosa. Other Problems of NSAIDs such as aspirin have an effect the kidneys, because the role of prostaglandins in the maintenance of blood flow to the kidneys, NSAIDs often cause kidney damage and disorders of salt and fluid balance. This article shows the adverse effects and mechanism of NSAIDs on the gastrointestinal tract. Mechanisms of gastrointestinal (GI) injury NSAIDs injure the gut by causing topical injury to the mucosa and systemic effects associated with  mucosal prostaglandin depletion derived from COX-1. The systemic effects of NSAIDs appear to have  the predominant role. Because of that the use of enteric-coated aspirin preparations and parenteral or rectal administration of NSAIDs in order to prevent topical mucosal injury has failed to prevent the development of ulcers. Topical injury The acidic properties of most NSAIDs (included ASA) initiate mucosal damage. These weak acids remain in their non ionised lipophilic form in the highly acidic gastric environment. These conditions favour migration into surface epithelial cell, where NSAIDs are dissociated into the ionised form that traps hydrogen ions, inducing mucosal injury. Systemic effects NSAIDs inhibit cyclooxygenase (COX), a key in the biosynthesis of prostaglandins. There are two isoforms, COX 1 and COX 2. Traditional NSAIDs (tNSAIDs) and ASA inhibit both isoforms. Selective NSAIDs (COXIBs) spare COX 1 and primarily inhibit COX 2. COX 1 isoform is expressed in most tissues, producing prostaglandins that play an important protective role in the gut by stimulating the synthesis and secretion of mucus and bicarbonate, increasing mucosal blood flow and promoting epithelial proliferation. When NSAIDs inhibit this enzyme create a gastric environment that is more susceptible to topical attack by endogenous and exogenous factors. Besides, the inhibition of the COX 1 blocks platelet production of thromboxane, which increases bleeding when an active GI bleeding site is present .On the other hand, COX2 isoform is induced inmost tissues in response to inflammatory stimuli. Prostaglandins derived from COX-2 can be generated at the ulcer margin and appear to play an important ro le in ulcer healing through triggering the cell proliferation, promotion of angiogenesis and restoration of mucosal integrity .This isoform is the primary target for anti-inflammatory drugs. Therefore selective COX-2 NSAIDs while having little to no effect on COX-1 should result in effective pain relief with reduced adverse GI effects. This COX2 hypothesis has been challenged by data from animal studies. Wallace et al reported that inhibition of both COX-1 and COX-2 is required for NSAID-induced gastric injury in the rat. Aspirin (acetylsalicylic acid) was first isolated in 1829 by Leroux from willow bark. It can cause irreversible inactivation of cyclo-oxygenase, acting on both COX-1 and COX-2. Aspirin has many pharmacologic effects for example it has antipyretic action it reduces fevers and is rapidly effective in febrile patients, yet has little effect on normal body temperature. It has many effects on the body; prostaglandin PGE2 is produced in the brain and causes the temperature regulatory centre in the hypothalamus to raise the body temperature, Aspirin inhibits PGE2 production so body temperature falls. Aspirin also has anti-inflammatory action, during inflammation, prostaglandin and other arachidonic acid are produced and contribute to the pain, swelling and tissue damage, and aspirin inhibits the production of arachidonic acid thus reducing inflammation. It is a very good anti-inflammatory effects it helps in condition for example the treatment of musculoskeletal disorders, such as rheumatoid arthritis, osteoarthritis and ankylosing spondylitis. The ability of aspirin to control pain occurs both through a peripheral and central action when aspirin inhibits the synthesis of prostaglandins in inflamed tissue, and it prevents the prostaglandin from sensitising the nociceptors, by inhibiting prostaglandin synthesis in the brain. Aspirin is also thought to also modify transmissions in the pain conducting pathways. Aspirin has other analgesic effects which is usually effective for low- to moderate-intensity pain. Integument pain is relieved better than the pain from hollow visceral areas. Relief of pain occurs through both peripheral and central mechanisms. In the peripherally, it inhibits the synthesis of PGs in inflamed tissues, thus preventing the sensitisation of pain receptors to both mechanical and chemical stimuli. Also in the centrally, the analgesic site exists in close proximity to the antipyretic region in the hypothalamus. Its analgesia action is not associated with mental alterations, such as hypnosis or changes in se nsation other than pain. EFFECTS OF ASPIRIN ON PROSTAGLANDIN SYNTHESIS Both COX-1 and COX-2 enzymes are inhibited by aspirin, but not by opioids, acetaminophen, or tramadol. The active site of both enzymes appears to be at the end of a long, tubular channel in the molecule. Aspirin block arachidonates entrance to this channel (as seen in picture below). Aspirin does this by irreversibly acetylating a specific serine molecule (serine 530 for COX-1 and serine 516 for COX-2) When blocked by aspirin, COX-1 becomes completely inactive. COX-2, on the other hand, converts arachidonate to 15-R-hydroxyeicosatetraenoic acid (15-R-HETE). Neither enzyme is capable of producing prostaglandin H2, the necessary precursor of prostaglandin and thromboxane synthesis. Aspirin causes damage to the gastric mucosa partly by inhibiting the formulation of prostaglandins that protect stomach wall from gastric acids. Aspirin in addition has Gastrointestinal effects such as It can cause epigastric distress, nausea, and vomiting by irritating the gastric mucosal lining and stimulating the chemoreceptor trigger zone in the CNS. It may cause a dose-related gastric ulceration, bleeding, and erosive gastritis because of inhibiting the formation of PGE2, which inhibits gastric acid secretion and has a cytoprotective effect. Salicylates-induced gastric bleeding is painless and may lead to an iron deficiency anemia. Aspirin is used in restricted situation for the symptomatic relief of fever. Because of an increased incidence of Reyes syndrome in children who previously were given aspirin for the relief of viral fevers, it is now recommended that a child with any fever be given paracetamol instead, if medication is required. It is useful as analgesics for certain categories of pain, such as headache, arthritis, and dysmenorrhea. It remains the standard, first-line drug in the therapy of rheumatoid arthritis, and can provide relief of symptoms in acute rheumatic fever. Some clinicians recommend small daily doses of aspirin for prophylaxis of thromboembolism, stroke, or myocardial infarction because of its antiplatelet activity. Some adverse effects of aspirin when uses in large repeated dosages are headache, mental confusion, lassitude, and drowsiness, tinnitus and difficulty in hearing, hyperthermia, sweating, thirst, hyperventilation, vomiting, and diarrhea. Contraindications Aspirin, non-steroidal anti-inflammatory drugs and anticoagulants should be avoided in all patients with liver disease because of the risk of altering platelet function, causing gastric ulceration and bleeding. NSAIDs have also been implicated in precipitating renal dysfunction and vericeal bleeding in patients with end-stage liver disease. Although COX-2 inhibitors may cause a lower incidence of bleeding complication, currently they are avoided in patients with liver disease as their still pose a risk. Paracetamol is an analgesic agent. It does not have ant-inflammatory or anti-platelet activities, but it is a useful analgesic in febrile illnesses such as influenza. As paracetamol has no anti-inflammatory properties it does not inhibit prostaglandin thus have no affect on the gastric mucosa. As an analgesic, paracetamol is best taken on an empty stomach for fast action, as it gets absorbed faster. As it is not associated with Reyess syndrome, it is the preferred analgesic in the symptomatic treatment of children with viral infections. The mechanism of action of paracetamol is now thought to be via COX-3 inhibition. This enzyme is present in the brain and spinal cord and is selectively inhibited by paracetamol. Paracetamol has no action on COX-1 and COX-2, thus does not have any gastric side effects. The central action of paracetamol explains it antipyretic effects and its lack of other peripheral adverse effects associated with NSAIDs. Paracetamol has few adverse side effects as it is tolerated by the stomach because inhibition of prostaglandin in the periphery is weak; allergic reactions and skin rash sometimes occur. Heavy, long term daily use may predispose chronic renal disease.

Computers :: essays research papers

Computers Nothing attracts a crowd like a crowd. Today, with home computers and modems becoming faster and cheaper, the home front is on the break of a new frontier of on line information and data processing. The Internet, the ARPANET (Advanced Research Programs Agency Network) spinoff is a channel of uninterrupted information interchange. It allows people to connect to large computer databases that can store valuable information on goods and services. The Internet is quickly becoming a tool for vast data interchange for more than twenty million Americans. New tools are allowing Internet presence an easier task. As did the gold miners set out to California on carriages to stake their claim in the gold rush, business and entrepreneurs are rushing to stake their claim on the information superhighway through Gopher sites, World-Wide Web sites, and electronic mailing lists. This article explains how businesses and entrepreneurs are setting up information services on the Internet that allows users to browse through picture catalogues, specification lists, and up to the minute reports. Ever since Sears Roebuck created the first pictorial catalogue, the idea has fascinated US that merchandises could be selected and ordered in our leisure time. Like any cataloging system, references make it easy to find what user seeks. Since its inception, The Internet has been refining its search tools. Being able to find products through many catalogues is what make the Internet shine in information retrieval. This helps the consumer find merchandise that they might other wise probably cannot find. The World Wide Web allows users to find information on goods and services, pictures of products, samples of music (Used by record Companies), short videos showing the product or service, and samples of programs. Although a consumer cannot order directly from the Web site, the business will often give a Voice telephone number or an order form that costumer can print out and send out through the mail. Although web sites have the magazine like appeal, storing large amounts of textual data is often difficult. Gopher (like go-for) is set up like a filing cabinet to allow the user more flexibility in retrieval. Gopher is similar to the white/yellow pages in the way information is retrieved word for word. They are also a lot cheaper and easier to set up which allows small business an easy way to set up shop. Consumers can find reviews, tech-info, and other bits and pieces of information. Each person who uses the Internet has an identification that sets them apart from everyone else. Often called handles (from the old short wave radio days). Electronic mail addresses allow information exchange from user to user.

Global Warming Challenge Essay

One of the greatest challenges earth is facing is Global Warming. The global warming hypothesis orginated in 1896 when Svante Arrhenius, a Swedish chemist, developed the theory that carbon dioxide emissions from the burning of fossil fuels would cause global temperatures to rise by trapping excess heat in the earth’s atmosphere. The term â€Å"Global Warming† signifies the temperature of the earth’s neon- surface air. The change in climatic conditions is one of the impacts of global warming. It is directly impacting on rising sea levels and the melting of ice. It is a threat to life on earth. The effects of global warming have been increasing significantly for the past decades. Climate change, devastation of the ecosystem, water contamination, melting ice over Arctic and Antarctic regions, negative impacts in the agricultural sector are just the problems caused by global warming. The reason behind this is human activities that lead to release of greenhouse gases. The concentration of greenhouse gases has significantly increased since 20th century. Some Scientists believe that there is an increase of 0.5 Celsius in earth’s temperature since 1900 and will continue to increase. The year 1990 was said to be the hottest year in the last century. We Human Beings have created an imbalance between life and nature that has led to flood, cyclones, landslides, tsunami, drought, etc. If this imbalance continues, soon our life on earth would be difficult. The increase of Carbon-dioxide in air is one of the reasons for warming the earth’s surface. The most significant greenhouse gas is actually water vapor, not something produced directly by humankind in significant amounts. However, even slight increases in atmospheric levels of carbon dioxide (CO2) can cause a substantial increase in temperature. When the earth’s surface warms up it will eventually lead to evaporation of water. Water vapor, itself is a greenhouse gas. It is believed that the increase in CO2 in the atmosphere will continue due to ongoing burning of fossil fuels and deforestation. Not only CO2 but other gases such as methane, CFCs, nitrous oxide, tropospheric ozone are also responsible for global warming. The increase in these gases is due to industrialization, deforestation, urbanization and increasing population. Nature has given us a mechanism to decrease the content of CO2 in atmosphere but we are exploiting it. Trees are the mechanism given to mankind as a gift from nature. Trees convert CO2 gas into Oxygen. This helps to decrease the CO2 content in atmosphere which eventually helps us prevent  global warming. The question that should be put forward now is that if this mechanism only won’t exist then how will we prevent global warming? Human beings have always been exploiting nature. Trees have been cut down for the benefits of humans without realizing that it is going to affect us eventually. Deforestation is responsible for 25 per cent of all carbon emissions entering the atmosphere, by the burning and cutting of 34 million acres of trees each year. Everyday over 5500 acres of rainforest are destroyed. Increasing population is also one of the reasons for global warming. Approximately, 80 per cent of atmospheric C02 increases are due to man’s use of fossil fuels either in the form of coal, gas or oil. Vehicles with poor gas mileage contribute the most to global warming. Besides, the sulphur group gas is the most harmful for this. Its contribution is 30 per cent in global warming. This gas is also emitted from the burning of fossil fuels. One of the effects of global warming is rise in sea-level. It will lead to melting of glaciers and changes in rainfall patterns. The rate of melting glaciers have been increasing since the past decade. . The shrinking of glaciers is going to pose a major problem of drinking water. The sea levels as a result of melting of glaciers have risen from 0.35 mm to 0.4 mm. Scientists have warned in their reports that most of the glaciers will disappear within a period of 15 to 25 years. It will create problems of drinking water and food grains in most of the North American countries. India is not unaffected from it. The Himalayan glaciers have shrunk about 30 per cent after 1970. The rise in sea levels is a major cause of concern. A large number of cities located in coastal areas will submerge in the sea. Besides, many island countries will ultimately lose their existence and will be washed away from the surface of the earth. In India this effects may also threaten the Lakshadweep islands, Mu mbai and deltas of Ganges (West Bengal), Carvers (T.N), Godavari (AP) and Mahanadi, Orissa. India is also affected by global warming. As India is an agricultural country, it is largely dependent on rainfall but due to irregular rainfalls caused by global warming, the yield is decreasing every year. The rise in atmospheric temperature and fall in rain would naturally result in decline in crop production. Moreover, it would have great effect on biodiversity as well. Forestation can be of great help in this regard. Planting more trees worldwide will help restore the imbalance. Secondly, we must follow on environmental policy of ‘reduce,  reuse, recycle’, i.e. promoting the reuse of anything. Thirdly, the use of fuel-efficient vehicles should be promoted as these vehicles have lower emissions of harmful gases. Fourthly, every individual should be aware of the importance of the protecting environment. Besides, eco- friendly technologies must be promoted, and must be substituted with the technologies which cause great emission of global warming gases. Many government agencies around the world are very interested in maintaining fossil fuel use, especially coal. Furthermore, we are not going to run out of coal in the near term (oil may begin to run low sometime after 2010). Methods for reducing carbon emission levels while still burning coal are now investigation by government and industry, as we now discuss. It is too late to debate on global warming. We need to take some measures to decrease global warming. Forestation can be of great help in this regard. Planting more trees worldwide will help restore the imbalance. Secondly, we must follow on environmental policy of ‘reduce, reuse, recycle’, i.e. promoting the reuse of anything. Thirdly, the use of fuel-efficient vehicles should be promoted as these vehicles have lower emissions of harmful gases. Fourthly, every individual should be aware of the importance of the protecting environment. Besides, eco- friendly technologies must be promoted, and must be substituted with the technologies which cause great emission of global warming gases. We should control the growth of population by decreasing birth rate. This can be done by proper family planning. We should reduce the use of chlorofloro carbons. More use of non-conventional source of energy like wind power and solar energy. It is said that â€Å"There is no place like home† and earth is our home so we need to protect it. Policies are made every day but do we follow it? The answer is â€Å"No†. We all are aware of global warming so we need to change the way we think that we can’t do anything and only the rich who are seated in the seats of government can save us. Who you are, whatever you are you can do something for your planet when you think global warming is a problem.

Annotated Bibliography On Criminal Justice System

Criminal Justice System The technological advancement era that has marred the 21st century has seen heightened increased surveillance and proactive crime investigations. Such growth has seen positive legislative moves that have allowed the use of telecommunication gadgets in monitoring trends of criminal activities and criminal gangs[footnoteRef:1]. Most commonwealth nation which United Kingdom is a member have since passed and enacted laws that provide some sort of immunities and exemptions for officers that may violate laws in the process of administering their works. [1: G. Marx, Undercover—Police Surveillance in America (University of California Press: Berkeley, 1988); and C. Fijnaut and G. Marx (eds.), Undercover—Police Surveillance†¦show more content†¦Consequently, the Canadian systems strives to strike a balance between crime control and prevention goals and equity, fairness, and protection of persons which are key to having a just system. Sweden on the other hand positions h er criminal justice system to reduce crime and secure her people[footnoteRef:3]. The Chinese system believes that a well functional society are key to having the right of every citizen protected. [3: ] World over, the criminal justice system work closely with undercover police units that are used to do unearth a series of sensitive evidence against law offender. By definition, undercover work as largely used is when police officers do not reveal their identities. As many opine, this form of policing takes a wider berth of forms and situation within which they operate. There is a general acknowledge among the justice system and the public on the need to have undercover policing in order to subvert threats to public safety such as terrorism Over the years, there have been ethical concerns over the works of undercover policemen both to the officers and those under study. The most essential to the system is the manner in which information is obtained and the more controversial is the means with which such information are obtained. Most laws have provisions that require undercover police and any other person within theShow MoreRelatedMental Health Disorders in the Criminal Justice System: Annotated Bibliography 2221 Words   |  9 Pagesof mental health disorders in the criminal justice system, prepared by Ogloff, J.R.P., Davis, M.R., Rivers, G. and Ross, S., Australian Institute of Criminology, Canberra. In this research bulletin commissioned by the Criminology Research Council, Ogloff et al. review the level of screening and the instruments used across jurisdictions to assess mental illness in justice agencies. Ogloff et al. intend to highlight the need and argue for a nationwide system of screening of all accused offendersRead MoreAnnotated Bibliography Of The Bibliography1341 Words   |  6 Pages1. 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