Pain Relief Using Nonsteroidal Anti Inflammatory Drugs Biology Essay

Introduction

NSAIDS1 ( Nonsteroidal anti-inflammatory drugs ) are drugs with the map of antipyretic, analgetic and anti-inflammation during a use of higher dosage. The name of Nonsteroidal is to separate from the steroidal agent which appears before NSAIDS. However, John Vane found out the basic mechanism of acetylsalicylic acid before the steroid was found. NSAIDS are a non-selective inhibitor. NSAIDS will suppress the enzyme Cox which include cyclooxygenase-1 ( COX-1 ) and cyclooxygenase-2 ( COX-2 ) . The Arachidonic acid has two metabolic tracts which are Cyclooxygenase pathway and lipooxygenase tract. Cyclooxygenase is an enzyme that will catalyze the production and formation of prostanoids Prostaglandin H2 by oxidization. The Prostaglandin H2 is so able to change over by specific enzyme to other Prostaglandins e.g. PGI2 and PGD2 etc. , which can move as go-between.this go-between is allowed to adhere to specific receptor on cell and advance different response.

Categorization

Harmonizing to the chemical construction, different types of NSAIDS are classified into different groups. They can be classified as Propionic acid derived functions ( e.g. isobutylphenyl propionic acid ) , Acetic acid derived functions ( e.g. Indomethacin ) , Enolic acid ( Oxicam ) derived functions ( e.g. Isoxicam ) , Fenamic acid derived functions ( e.g. Fenamic acerb derived functions ) and Selective COX-2 inhibitors ( e.g. Rofecoxib which was withdrawn from the market ) . A similar tolerability and features ( e.g. half life ) will be shown with the same group of NSAIDS. While Aspirin is a irreversible inhibitor but isobutylphenyl propionic acid and diclofenac are reversible.

Pain

Is defined as, ” an unpleasant sensory and emotional experience associated with existent or possible tissue harm, or described in footings of such harm. ” by the international association for the survey of hurting ( ISAP ) 9. Trouble can be merely classified as fast hurting and decelerate hurting. In add-on, the fast hurting urges and decelerate hurting urges are transmitted through AI? fiber and C fiber severally.

We Will Write a Custom Essay Specifically
For You For Only $13.90/page!


order now

Pain pathway8

The hurting tract is a bipartisan traffic tract with falling tract and go uping pathway. The falling tract gives an repressive consequence of hurting esthesis. The falling tract is from the witting encephalon to the subconscious encephalon and spinal cord, which is the topographic point that allows the control and gating of the hurting messages fluxing to the intellectual cerebral mantle ( Gate theory ) .

In general, hurting is caused by potentially damaging stimulations which stimulates the nociceptor. The stirred nociceptor will so direct hurting message ( signal urge ) through the go uping tract to intellectual cerebral mantle by web of relay nerve cell. This procedure is called nociception which cause the hurting esthesis.

Therefore Nociceptor is besides called hurting receptor. The activation of nociceptor caused by different type of inflammatory go-betweens e.g. Bradykinin, Prostaglandins etc. moving to it from the extracellular fluid.

The Prostaglandin is an inflammatory go-between. They are produced in every nucleated cell except lymph cells cell of our organic structure.

Prostaglandin, which consists of 20 C atoms, is lipid compound and is produced enzymatically from fatty acids of Membrane Phospholipids.

First membrane phospholipids react with cPLA2 ( Ca2+-dependent ) ( Phospholipases A ) . cPLA2 is an enzyme that will let go of the fatty acerb signifier the membrane phospholipids by hydrolysis. This causes the formation of Arachidonic acid. The Arachidonic acid is so brought to a Cox tract. In the Cox tract, Arachidonic acid is being oxidized by COX-1 and COX-2, which both are Cox and located at blood vass, tummy and the kidneys, into Prostaglandin H2 ( PGH2 ) . In add-on COX-1 operate the production of prostaglandins at the baseline degree, which COX-2 is responsible for the production of prostaglandins when there is a stimulation e.g. redness. Prostaglandin H2 ( PGH2 ) which is biologically inactive prostaglandins. It needs to be activated by PGE synthase and PGD synthase to bring forth biologically active prostaglandins PGE2 and PGD2. As a consequence, during redness prostaglandin degrees are increased as the COX-2 is being activated by the stimulation. The increased sum of prostaglandin released from the cell will move as go-between when adhering to nociceptor alternatively of being pain go-between. More significantly is the addition in the sensitiveness of nociceptors to other go-between. As a consequence the usually non-excitable ‘silent nociceptor ‘ is switched into a more easy excitable province. The aroused receptor will so direct a hurting message ( impulse ) to the encephalon via an go uping tract.

Function3

Analgesic

Nonsteroidal anti-inflammatory drugs normally act as inhibitors which non-selectively inhibit both COX-1 and COX-2. As we know the Cox catalyses the formation of prostaglandins. Therefore, NSAIDS inhibit and cut down the formation of prostaglandin from Arachidonic acid. NASIDS consequence in decreased hurting go-between and sensitiveness of nociceptor. This could account for the hurting alleviation by NSAIDS.

Aspirin is a good illustration of NSAIDs. The acetylsalicylic acid has an ethanoyl group group which is hydrolysed and bound to the serine of at the intoxicant group of the COX enzyme as an ester. This procedure will barricade the particular site ( channel ) of the enzyme. As a consequence the Arachidonic acid is non allowed to acquire into the active site, therefore no prostaglandin is produced.

Antipyretic

Caused by the increasing the degree of prostaglandin E2, which will increase the firing rate of nerve cell of hypothalamus which disrupts the normal map of it. As the hypothalamus is the centre of thermoregulation as a consequence of organic structure temperature addition. NSAIDS will suppress the formation of E2 and lower the organic structure temperature

Side Effectss of NSAIDS5

As we know NSAIDS is a non-selective inhibitor. The maps of COX-1 is of import which involve homeostatic procedure, thrombocyte collection, nephritic map, influences Kidney map and maintain normal stomachic mucous membrane.The mucous membrane protection by COX-1 is cut down by the NSAIDS side effects which will do Gastric ulcer and GI hemorrhage. Peoples who suffer from RA and OA need to continuously intake NSAIDS to relief hurting and anti- redness will hold GI side consequence.

Scientists want to contrive a new medical specialty that could extinguish the side effects caused by the suppression of COX-1.

In 1991 the scientists of Merck & A ; Co. invented a medical specialty called Rofecoxib. This drug is a selective COX-2 inhibitor. Therefore it can greatly cut down the hazard of Gastric ulcer and GI hemorrhage.

In VIGOR ( Vioxx GI Outcome research ) survey, they compare the efficaciousness and inauspicious side consequence of Rofecoxib and the NSAID Naprosyn. For the efficaciousness, the consequence shows a significantly fewer side consequence of GI Gastric ulcers and other upper GI events cut down from 54 % , to 1.4 % , while the GI piece of land shed blooding reduces by 62 % when compared to naproxen group. In add-on, there are a smaller per centum of people received a gastro-protective medical specialty which holding Vioxx than naproxen group. On the other manus, the consequence of over 12 months span shows that the patients with Rofecoxib intervention have a 4 times increased hazard of enduring from acute myocardial infarction that patients with Naprosyns. They claim that there is no important informations show with the patients without high hazard of cardiovascular, but merely with high hazard of cardiovascular patients.

Merck ‘s scientists claim that as the Naprosyn has a protective consequence, but at that clip there is no grounds shows that there are such big protective effects ( anti-platelet consequence ) to bosom onslaught from Naprosyn.Therefore when Vioxx broad appear, it is being widely accepted by the universe market and patient due to its ain benefits.

After the entry of VIGOR survey to the US Food and Drug Administration, it leads to debut of Vioxx into the market in 2001, and so requested to demo the warning of increasing inauspicious cardiovascular event in 2002.

In fact, before the VIGOR was published, the inauspicious cardiovascular events were taken out from the article. There were 3 extra bosom onslaughts which occur within the low hazard cardiovascular group and increase the hazard of cardiovascular event by 4 to 5 times.

In 2001 Merck made another 3 twelvemonth test survey ‘the APPROVe survey ‘ . One of the purposes of this survey is in order to demo if the Vioxx is cardiovascular safe. It was shown that in this survey there will be about two times more opportunity in Vioox group when compared to NSAIDs group of acquiring a cardiovascular event.

As proven by the APPROVe survey which is the survey of its ain. On 30 of September 2004 Merck voluntarily withdrew the medical specialty from the international market.

Decision

When a research survey is made to the populace, it is of import that both the efficaciousness and adverse said consequence demand to be to the full disclosed but non merely the favourable consequences. We can non manufacture consequences

If any of the consequences is concealed, it will be disapproved and the merchandises will be withdrawn from the market.

Actually by the survey of omerprazole and NSAIDS, utilizing omerprazole, which is a proton pump inhibitor, together with NSAIDS is able to cut down the GI side consequence to 20 % . As a consequence NSAIDS are able to utilize safer and give a less inauspicious side consequence to the patient.