INTRODUCTION In our so called developing country where we are aping the west and putting forth a strong competition

in all aspects, there is still one aspect where we lag behind phenomenally and that is, we can purchase almost any drug we want without a legal prescription at any pharmacy. People just pop pills without knowing their adverse effects or for how long they should be taking it. Now this, could lead to serious drug abuse. Among this lot, only a few conscious individuals visit a doctor with symptoms of pain and then from our perspective pain management strategy is of utmost importance. There are basically categories of pain control medication they are ! "# Narcotics $steroidal# %# Aspirin and other N&AI'& # Acetaminophen HISTORY : (illow )ark $&ali* alba# has been used for many centuries as a analgesic and antipyretic. &alicylic acid was obtained by hydrolysis of the bitter glycoside obtained from this plant.

&odium salicylate was used for fever and pain in "+,-. Its success led to the introduction of acetyl salicylic acid $aspirin# in "+...

Phenacetin and antipyrine also introduced at the same time.

"./. 0 development of phenylbuta1one ".2 0 Indomethacin was introduced ".2 onwards 0 Propionic acid derivatives referred to as N&AI'3s have been introduced along with some selective 4567% inhibitors. ".," 0 vane and coworkers observed that N&AI'3s blocked P8 synthesis

CLASSIFICATION According to Tripathy: A. Analg !ic and anti"in#la$$atory : ". &alicylates 0 aspirin, salicylamide, benorylate, diflunisal %. Pyra1olone derivatives 0 phenylbuta1one, o*yphenbuta1one . Indole derivatives 0 indomethacin, sulindac /. Proprionic acid derivatives 0 ibuprofen, napro*en, ketoprofen, fenoprofen, flurbiprofen. -. Anthranilic acid derivative 0 mephenamic acid 2. Aryl acetic acid derivatives 0 declofenac, tolmetin

,. o*icam derivatives 0 piro*icam, teno*icam, melo*icam +. Pyrrolo7pyrrole derivative 0 ketorolac .. &ulfonanilide derivative 0 nimesulide "9. Alkanones 0 Nabumetone %. Analg !ic &'t poor anti"in#la$$atory : ". Paraaminophenol derivatives 0 paracetamol $acetaminophen# %. Pyra1olone derivative 0 metami1ol $dipyrone#, propiphena1one . )en1o*a1ocine derivative 0 nefopam. Cla!!i#ication according to (ood$an and (ill$an : Non ! l cti) CO* inhi&itor! : a# b# c# d# e# f# g# h# &alicylic acid derivatives 0 aspirin, sodium salicylate, choline magnesium trisalicylate, salsalate, diflunisal, sulfasala1ine, olsala1ine. Para amino derivatives 0 acetaminophen Indole and indene acetic acid 0 indomethacin, sulindac :eteroaryl acetic acid 0 tolmetin, diclofenac, heterolac. Aryl propionic acid 0 thioprofen, napro*en, flurbiprofen, hetoprofen, tenoprofen, o*apro1in. Anthranilic acid $fenamates# 0 mefenamic acid, meclofenamic acid ;nolic acids 0 o*icam $piro*icam, melo*icam# Alkanones 0 Nabumetone. a# 'iaryl substituted furanones 0 rofeco*ib b# 'iaryl substituted pyro1oles 0 celeco*ib c# Indole acetic acids 0 etodolac d# &ulfonanilides 0 Nimesulide ,-CHANIS, OF ACTION : <rom a dental perspective, the most common type of odontogenic pain is characteri1ed by acute pain and the most common management approach is a pharmacological one. The initial event for most acutely painful conditions is a no*ious stimulus that results in tissue destruction or injury. The trauma may be initiated by a disease process, such as an apical abscess or by surgical intervention, such as e*traction of a tooth. In either case the resultant cellular destruction causes the release or synthesis of several biochemical mediators involved in the pain process i.e. histamine, prostaglandins and bradykinin. These and other substances interact with peripheral nociceptors $pain receptors# and free nerve endings to trigger pain signals from the area of tissue injury.

S l cti) CO*"+ inhi&itor :

The prostaglandins particularly the ; type cause hyperalgesia by sensiti1ing afferent nociceptors in the periphery to other algsesic mediators, such as histamine and bradykinin. 5nce these primary afferent fibres in the oral cavity and face are stimulated beyond a threshold level, impulses are sent to the 4N& along A and 4 fibres of the trigeminal, facial, glossopharyngeal and vagus nerves to the trigeminal nucleus caudalis in the medulla and higher centers where they are decoded and interpreted and appropriate responses are made. Peripherally acting analgesics reduce and control pain by directly inhibiting the biochemical mediators of pain at the site of injury. The primary mechanism of action of the peripherally acting analgesics is inhibition of the cycloo*ygenase en1yme system that metaboli1es arachidonic acid to its endopero*ide intermediates. 5nce formed the endopero*ides are converted to thrombo*anes, prostacyclins and prostaglandins. some evidence suggests that several peripherally acting analgesics may own their e*ceptional efficacy not only to a more effective inhibition of important isoen1ymes of the cycloo*ygenase system at the site of injury but also to secondary effects of cycloo*ygenase inhibitor within the 4N&. The spinal dorsal horn is a probable site of action of N&AI's and may involve mechanisms other than inhibiton of cyclo o*ygenase. %-N-FICIAL ACTIONS DU- TO .( SYNTH-SIS INHI%ITION Analgesia Antipyresis Antinflammatory 4losure of ductus arteriosus

SHAR-D TO*ICITI-S DU- TO .( SYNTH-SIS INHI%ITION 8astric mucosal damage )leeding =imitation of renal blood flow 'elay>prolongation of labour Asthma and anaphylactoid reactions

CO,,ON .RO.-RTI-S OF ALL NSAIDS : /0 Analg !ia P8s induce hyperalgesia . N&AI's do not affect the tenderness induced by direct application of P8s, but block the pain sensiti1ing mechanism induced by bradkinin,

TN< interleukins $Ils# and other algesic substances. They are therefore more effective against inflammation associated pain. +0 Antipyr !i! N&AI's reduce body temperature in fever, but do not cause hypothermia in normothermic individuals. <ever during infection is produced through generation of pyrogen, Ils, TN<, interferons which induce P8 production in hypothalamus 0 raise its temperature set point. N&AI's block the action of pyrogens. 10 Anti in#la$$atory Antinflammatory action of N&AI's is considered to be inhibition of P8 synthesis at the site of injury. 20 Dy!$ norrho a Involvement of P8s in dysmenorrhoea has been clearly demonstrated. level of P8s in menstrual flow, endometrial biopsy and that of P8<% metabolite in circulation are raised in dysmenorrhoeic women. Intermittent ischaemia of the myometrium is probably responsible for menstrual cramps. N&AI's lower uterine P8 levels 0 afford e*cellent relief in 29 0 ,9?. 30 Antiplat l t aggr gatory NA&I's inhibit synthesis of both proaggregatory $T6A%# and antiaggregatory $P8I%# prostanoids, but effect on platelet T6A% predominates. Therapeutic doses of most N&AI's inhibit platelet aggregation. )leeding time is prolonged. 40 D'ct'! art rio!'! clo!'r 'uring foetal circulation ductus arteriosus is kept patent by local elaboration of P8; % and P8I%. @nknown mechanisms switch off this synthesis at birth and the ductus closes. (hen this fails to occur, small doses of indomethacin or aspirin bring about closure in majority of cases within few hours by inhibiting P8 production. Administration of N&AI's in late pregnancy has been found to promote premature closure of ductus in some cases.

50 .art'rition &udden spurt of P8 synthesis by uterus probably triggers labour. N&AI's delay and retard labour.

60 (a!tric $'co!al da$ag 8astric pain, mucosal erosion>ulceration and blood loss are produced by all NA&I's to varying e*tents. Inhibition of synthesis of gastroprotective P8s $P8; %, P8I%# is clearly involved, though, local action inducing back diffusion of : A ions in gastric mucosa also plays a role. 'eficiency of P8s reduces mucus and :45 7 secrection, tends to enhance acid secretion and may promote mucosal ischaemia. 70 R nal ## ct! 4onditions leading to hypovolemia, decreased renal perfusion and NaA loss induce renal P8 synthesis which brings about intrarenal adjustments by promoting vasodilatation, inhibiting tubular 4l7 reabsorption and opposing A': action. Benal effects of N&AI's are not marked in normal individuals but significant in those with 4:<, hypovolemia, hepatic cirrhosis, renal disease and those receiving diuretics or antihypertensives NaA retention and edema can occur, diuretic and antihypertensive effects are blunted. /80 Anaphylactoid r action! Aspirin precipitates asthma, angioneurotic swellings, urticaria or rhinitis SALICYLAT-S Aspirin $prototype# Aspirin is acetylsalicylic acid .Bapidly converted in the body to salicylic acid which is responsible for most of the actions. .HAR,ACOLO(ICAL ACTIONS /. analg !ic9 antipyr tic9 anti"in#la$$atory action! Aspirin is a weaker analgesic than morphine type drugs. Aspirin 299 mg codeine 29 mg. It relieves inflammatory, tissue injury related, connective tissue and integumental pain but is relatively ineffective in severe visceral and ischaemic pain. Aspirin resets the hypothalamic thermostat and rapidly reduces fever by promoting heat loss. Antinflammatory action is e*erted at high doses $ 72 g>day or "99 mg>kg>day#. &igns of inflammation are suppressed. +. , ta&olic ## ct! &ignificant only at antinflammatory doses. 4ellular metbolism is increased in skeletal muscles, due to uncoupling of o*idative phosphorylation increased heat production Increased utili1ation of glucose blood sugar may decrease liver glycogen is depleted. :yperglycaemia is often seen at to*ic doses. This is due to central sympathetic stimulation release of Adrenalin and corticosteroids. 4hronic use of large

doses causes negative N% balance by increased conversion of protein to carbohydrate. Plasma free fatty acid and cholesterol levels are reduced. 1. R !piration At antinflammatory doses respirations is stimulated by peripheral $increased 45% production# and central $increased sensitivity of respiratory center to 45%# actions. 2. acid &a! and l ctrolyt &alanc Antinflammatory doses produce significant changes in the acid7base and electrolyte composition of body fluids. Initially respiratory stimulation predominates and tends to wash out 45% despite increased production C respiratory alkalosis, which is compensated by increased renal e*cretion of :45 . Dost adults treated with /72 g>day of aspirin stay in a state of compensated respiratory alkalosis. &till higher doses cause respiratory depression with 45 % retention, while e*cess 45% production continues respiratory acidosis. To this are added dissociated salicylic acid as well as metabolic acids which are produced in e*cess A metabolically derived sulfuric and phosphoric acid which are retained due to depression of renal function. All these combine to cause uncompensated metabolic acidosis . 3. C:S Aspirin has no direct effect in therapeutic doses. =arger doses increase cardiac output to meet increased peripheral 5 % demand and cause direct vasodilatation. To*ic doses depress vasomotor center! )P may fall. 4:< may be precipitated. 4. (IT Aspirin and released salicylic acid irritate gastric mucosa cause epigastric distress, nausea and vomiting. 5. Urat ;cr tion < % g>day 0 urate retention and antagonism of all other uricosuric drugs. %7- g>day 0 variable effects, often no change. E - g>day 0 increased urate e*cretion. 6. %lood Aspirin, even in small doses, irreversibly inhibits T6A% synthesis by platelets. .HAR,ACO=IN-TICS Aspirin is absorbed from stomach and small intestines. Aspirin is rapidly deacetylated in the gut wall, liver, plasma and other tissues to release salicylic acid. It is +9? bound to plasma proteins and has a volumes of distribution 09.", =>kg. It slowly enters brain but freely crosses placenta.

The plasma tF of aspirin as such is "-7%9 min, that of released salicylic acid, it is 7- hours. Anti7inflammatory doses may be +7"% hours while that during poisoning may be upto 9 hours. AD:-RS- -FF-CTS a0 Sid ## ct! At analgesic dose $9. 7".- g>day# 7 nausea, vomiting, epigastric distress, increased occult blood loss in stools. 8astric mucosal damage and peptic ulceration. b# Hyp r! n!iti)ity and idio!yncra!y Beactions include rashes, fi*ed drug eruption, urticaria, rhinorrhoea, angioedema, asthma and anaphylactoid reaction. Profuse gastric bleeding. c0 Antin#la$$atory do! ! Produce the syndrome called salicylism which includes di11iness, tinnitus, vertigo, reversible impairment of hearing and vision, e*citement and mental confusion, hyperventilation and electrolyte imbalance. d0 Ac't !alicylat poi!oning Dore common in children. <atal dose in adults is "-7 9 g. serious to*icity is seen at serum salicylate levels E -9 mg>dl. Danifestations are! Gomiting, dehydration, electroyte imbalance, acidotic breathing, restlessness. 'elirium, hallucinations, hyperpyre*ia, convulsions, coma and death due to respiratory failure A cardiovascular collapse. .r ca'tion! and contraindication! Aspirin is contraindicated in patients who are sensitive to it and in peptic ulcer, bleeding tendencies, in children suffering from chicken po* or influen1a. 'ue to risk of Beye3s syndrome pediatric formulations of aspirin are prohibited in India and @.H. In chronic liver disease! cases of hepatic necrosis have been reported. It should be avoided in diabetics. In those with low cardiac reserve or frank 4:< and in juvenile rheumatoid arthritis. Aspirin should be stopped " week before elective surgery. 8iven during pregnancy it may be responsible for low birth weight babies. 'elayed or prolonged labour, greater postpartum blood loss and premature closure of ductus arteriosus. It should be avoided by breast feeding mothers. Avoid high doses in 872 P' deficient individuals 0 haemolysis can occur.

Int raction! ". It displaces warfarin, napro*en, sulfonylureas, phenytoin and methotre*ate from binding sites on plasma proteins! to*icity of these drugs may occur. Its antiplatelet action increases the risk of bleeding in patients on oral anticoagulants. %. . /. US-S ". As analgesic for headache, backache, myalgia, joint pain, pulled muscle, toothache, neuralgias and dysmenorrhoeaI it is effective in low doses $9. 79.g > 27+ hourly#. %. As antipyretic . Acute rheumatic fever /72g or ,-7"99 mg>kg>day it brings about marked symptomatic relief in "7 days. 'ose reduction may be started after /7, days and maintenance doses $-9 mg>kg>day# are continued for %7 weeks or till signs of active disease persist. (ithdrawal gradual over the ne*t % weeks. /. Bheumatoid arthritis -. 5steoarthritis. 2. Postmyocardial infarction and poststroke patients by inhibiting platelet aggregation it may lower the incidence of reinfarction. /97 %- mg>day JNew onset3 or Jsudden worsening3 angina 99 mg aspirin per day for "% weeks. ,. 5ther less established uses ! a# Pregnancy induced hypertension and Preeclampsia b# 'elay labour c# Patent ductus arteriosus ! closure > AS.IRIN9 DIS.RIN9 ASA%UF 0 .YRA?OLON-S /. .h nyl&'ta@on It is a more potent anti7inflammatory comparable to corticosteroids. The analgesic and antipyretic action is poorer and slower in onset. It is uricosuric by virtue which inhibits renal tubular reabsorption of uric acid. 4auses definite retention of Na A It inhibits tubular secretion of uric acid and antagoni1es uricosuric action of probenecid. Tubular secretion of methotre*ate is also interfered. It blunts diuretic action of furosemide and thia1ides and blocks the action of spironolactone. Beduces protein bound iodine levels by displacement of thyro*ine

and water by direct action on renal tubules edema, e*pansion of plasma volume occur after "7% weeks of use. 4:< may be precipitated. .har$acoAin tic! 4ompletely absorbed orally. It is .+? bound to plasma proteins. completely metaboli1ed in liver by hydro*ylation and glucuronidation. The plasma t F is 29 hours. Do! ! "997%99 mg )' or T'& after meals. ?OLANDIN Ad) r! ## ct! ! more to*ic than aspirin. Nausea, vomiting, epigastric distress and peptic ulceration. 'iarrhoea and a variety of 4N& side effects. :ypersensitivity! rashes, serum sickness, hepatitis and stomatitis. )one marrow depression, agranulocytosis &tevens 0 Kohnson syndrome. 8oiter and hypothyroidism Int raction! : displaces sulfonamides, tolbutamide, warfarin, imipramine and methotre*ate from protein binding sites. Bisk of bleeding is increased in patients on anticoagulants. It is an inducer of microsomal en1ymes! increases its own metabolism as well as that of many drugs and steroids. It competitively inhibits phenytoin and tolbutamide metabolism. U! ! ". @sed only in severe cases that does not responding to other drugs. Bheumatic arthritis and ankylosing spondylitis. %. Bheumatic fever . Acute gout +. o;yph n&'ta@on Dajor metabolite of phenylbuta1one, SIORIL9 .H-NA%ID "99,%99 mg tab. 1. , ta$i@ol >Dipyron 0 'erivative of amidopyrine it is a potent and promptly acting analgesic and antipyretic but poor anti7inflammatory. It can be given orally, i.m. as well as i.v. but gastric irritaion, pain at injection site occurs. 5ccasionally i.v. injection produces precipitous fall in )P. 'ose ! 9.-79.".- gI ANAL(IN9 NO:AL(IN 2.propiph na@on Another pyra1olone, similar in properties to metami1ol, claimed to be better tolerated. 'ose ! 997299 mg T'&I SARIDON9 ANAF-%RIN

INDOL- D-RI:ATI:-S Potent anti7inflammatory drug, and promptly acting antipyretic. Analgesic action is better than phenylbuta1one, but relieves only inflammatory or tissue injury related pain. .har$acoAin tic!! well absorbed orally, rectal absorption is slow but dependable. .9? bound to plasma proteins, plasma t F is %7- hours. Ad) r! ## ct! : Darked gastric irritation, nausea, anore*ia, gastric bleeding and diarrhoea. <rontal headache, di11iness, ata*ia, mental confusion, hallucination, depression and psychosis. =eukopenia, rashes and other hypersensitivity reactions are also reported. Increased risk of bleeding due to decreased platelet aggregability. 4ontraindicated in machinery operators, drives, psychiatric patients, epileptics, kidney disease, pregnant women and in children. Int raction! : )lunts the diuretic action of furosemide. 'ecreases the antihypetensives effects of thia1ides, furosemide, lockers and A4; inhibitors. 'isplaces warfarin from protein binding sites. 'ose ! %-7-9 mg )'7LI'. IDICIN9 INDOCA. U! ! : Indicated in rheumatoid arthritis, ankylosing spondylitis, acute e*acerbations of destructive arthropathies and psoriatic arthritis, acute gout. Dalignancy associated fever, closure of patent ductus arteriosus, three "% hourly doses of 9."79.% mg>kg. .RO.IONIC ACID D-RI:ATI:-S Ibuprofen was the first member of this class to be introduced in ".2.. Analgesic, antipyretic and anti7inflammatory efficacy is rated somewhat lower than high dose of aspirin. Napro*en being most potent. Ad) r! vomiting. 4N& side effects include headache, di11iness, blurring of vision, tinnitus and depression. Bashes, itching and other hypersensitivity phenomena are infreMuent. Precipitates aspirin induced asthma. <luid retention is less marked not to be prescribed to pregnant women and in peptic ulcer patient. ## ct! : ;ffects are milder and their incidence is lower. 8astric discomfort, nausea and

.har$acoAin tic! and Int raction! : (ell absorbed orally, highly bound to plasma proteins $.97..?#, displacement interactions are not clinically significant. @se with anticoagulants should be avoided. They are likely to decrease diuretic and antihypertensive action of thia1ides, furosemide and blockers. U! ! : ". &imple analgesic and antipyretic. ;ffective in dysmenorrhoea. Its a Jover the counter3 drug. %. (idely used in rheumatoid arthritis, osteoarthritis and other musculoskeletal disorders. . &oft tissue injuries, fractures, vasectomy, tooth e*traction, postpartum and post operatively Dr'g Ibuprofen .la!$a t B % hr Do!ag /997+99 mg T'& .r paration! )B@<;N, ;D<=AD, Napro*en "%7"2 hr %-9 mg )'7T'& I)@&NNT: NAPB5&NN, NA6I', ABTA8;N, Hetoprofen <enoprofen <lurbiproen %7 hr %7/ hr /72 hr "99mg )'7T'& 997299mg T'& -9mg )'7LI' 6;N5)I' H;T5<;N, B:5<;NI' AB<=@B

ANTHRANILIC ACID D-RI:ATI:- >F-NA,AT-0 , ph na$ic acid : An analgesic, antipyretic and anti7inflammatory drug, known from ".-9s, but has not gained popularity because of lower efficacy. Ad) r! ## ct! : ;pigastric distress, skin rashes, di11iness and other 4N& manifestations. :aemolytic anaemia is rare but serious complication. .har$acoAin tic! : 5ral absorption is slow but almost complete. :ighly bound to plasma proteins 0 displacement interactions can occurI plasma t F is %7/ hours. U! ! : Analgesic in muscle, joint and soft tissue pain, dsymenorrohea, rheumatoid and ostearthritis Do!ag : %-97-99mg T'&I ,-DOL9 ,-FTAL9 .ONSTAN ARYL"AC-TIC ACID D-RI:ATI:-S :

Diclo# nac !odi'$ : A newer analgesic7antipyretic7antiinflammatory drug, similar in efficacy to napro*en. (ell absorbed orally, ..? protein bound, metaboli1ed and e*creted both in urine and bile. Plasma t F is 0% hours. Ad) r! ## ct : are generally mild! epigastric pain, nausea, headache, di11iness, rashes. 8astric ulceration and bleeding are less common. Its indications are similar to those of ibuprofen7rheumatoid and osteoarthritis, bursitis, ankylosing spondylitis, dysmenorrhoea, post7traumatic and postoperative inflammatory conditions. Do! ! -9 mg T'&, then )' oral, ,- mg deep i.m. :O:-RAN9 DICLONAC9 ,O:ONAC9 TOL,-TIN. O*ICA, D-RI:ATI:-S piro;ica$ : It is a novel long acting potent N&AI' with anti7inflammatory potency similar to indomethacin and good analgesic7antipyretic action. .har$acoAin tic! : Bapidly and completely absorbed! ..? plasma protein bondI plasma t F is long 0 nearly % days. &ingle daily administration is sufficient. Ad) r! ## ct! : :eart burn, nausea and anore*ia. ;dema and reversible a1otemia. U! ! :Bheumatoid and osteo 0 arthritis, ankylosing spondylitis, acute gout, musculoskeletal injuries, dentistry, episiotomy, dysmenorrhoea.

Do! ! %9 mg )' for two days followed %9 mg 5'! DOLON-*9 .IRO* TOLDIN9 .IRICA, T no;ica$ : A congener of piro*icam with similar properties and uses. TO%ITIL , lo;ica$ : Becently developed congener of piro*icam, has greater in vitro and vivo inhibitory action against the inclucible 4567%, which is implicated in the inflammatory response, than against the 4567", currently marketed for treatment of rheumatoid and osteo7arthritis in a dose of ,.-7"- mg>day. 4onsidering its better gastric tolerability, melo*icam may prove to be an advancement. .YRROLO .YRROL- D-RI:ATI:- : = torolac : A novel N&AI' with potent analgesic and modest anti7inflammatory activity. In postoperative pain it has eMualed the efficacy of morphine. Is rapidly absorbed after oral and i.m. administration. It is highly plasma protein bound and 29? e*creted unchanged in urine. Plasma t F is -7, hours. Ad) r! ## ct! : Nausea, abdominal pain, dyspepsia, ulceration, loose stools, drowsiness, headache, di11iness, nervousness, pruritus, pain at injection site, rise in serum transaminase and fluid retention. It should not be given to patients on anticoagulants. U! : used in postoperative and acute musculoskeletal pain. "-7 9 mg i.m. every /72 hours $ma*. "%9 mg>day#. It may also be used for renal colic, migraine and pain due to bony metastasis.

5rally it is used in a dose of "97%9 mg 2 hourly continuous use for more than - days is not at present recommended. =-TOROL9 ?ORO:ON9 =-TANO:9 TOROLAC. SULFONANILID- D-RI:ATI:- : Ni$ !'lid : this newer N&AI' is a relatively weak inhibitor of P8 synthesis $may be somewhat selective for 4567%#I appears to e*ert its effects by other mechanisms like reduced generation of supero*ide by neutrophils, inhibition of PA< synthesis and TN< release, free radical scavenging, inhibition of metalloproteinase activity in cartilage.. the analgesic, antipyretic and anti7inflammatory activity of nimesulide has been rated comparable to other N&AI's. @sed primarily for short lasting painful inflammatory conditions like sports injuries, sinusitis and other ear7nose7throat disorders, dental surgery, bursitis, low backache, dysmenorrhoea, postoperative pain and osteoarthritis. Ad) r! ## ct! : are gastrointestinal $epigastrelgia, heart burn, nausea, loose motions#, dermatological $rash, pruritus# and central $somnolence, di11iness#. Nimesulide is almost completely absorbed orally ..? plasma protein bound, e*tensively metaboli1ed and e*creted mainly in urine with at t F of %7- hours. Do! : "99mg )'C NI,ULID9 NI,-(-SIC9 NI,ODOL. .ARA"A,INO .H-NOL D-RI:ATI:-S : Phenacetin was introduced in "++,. )ut is now banned because it was implicated in analgesic abuse nephropathy. .arac ta$ol $acetaminophen# the deethylated active metabolite of phenacetin, was also introduced in the last century but has come into common use only since ".-9. Action! : The central analgesic action of paracetamol is like aspirin, i.e. it raises pain threshold, but has weak peripheral anti7inflammatory component. Analgesic action of aspirin and paracetamol is additive. Paracetamol is a good and promptly acting antipyretic. Paracetamol has negligible antiinfllammatory action. It is a poor inhibitor of P8 synthesis in peripheral tissues, but more active on 456 in brain. In contrast to aspirin, paracetamol does not stimulate respiration or affect acid7 base balance. 'oes not increase cellular metabolism. It has no effect on 4G&. 8astric irritation is insignificant. It does not affect platelet function or clotting factors and is not uricosuric. .har$acoAin tic! : Paracetamol is well absorbed orally, only about "> is protein bound in plasma and uniformly distributed in the body. Plasma t F is %7 hours. ;ffects after an oral dose last 7- hours.

Ad) r!

## ct! ! In isolated antipyretic doses paracetamol is safe and well tolerated.

Nausea and rashes occur occasionally, leukopenia is rare. Analgesic nephropathy occurs after years of heavy ingestion of analgesics. It manifests as papillary necrosis, tubular atrophy followed by renal fibrosis. @rine concentrating ability is lost and the kidneys shrink. Ac't parac ta$ol poi!oning : It occurs specially in small children who have low hepatic glucoronide conjugating ability. If a large dose $ E "-9 mg > kg or E "9 g in an adult# is taken, serious to*icity can occur. <atality is common with E %-9 mg>kg. ;arly manifestations are just nausea, vomiting, abdominal pain and liver tenderness with no impairment of consciousness. After "%7"+ hours centrilobular hepatic necrosis occurs which may be accompanied by renal tubular necrosis and hypoglycemia that may progress to coma. Kaundice starts after % days. <ulminating hepatic failure and death are likely if the plasma levels are above the line joining %99 g>ml at / hours and 9 g>ml at "- hours. , chani!$ o# to;icity : N7acetyl7ben1oMuinone7imine is a highly reactive arylating minor metabolite of paracetamol which is deto*ified by conjugation with glutathione. (hen a very large dose of paracetamol is taken, glucuronidation capacity is saturated, more of minor metabolite is formed 0 hepatic glutathione is depleted and this metabolite binds covalently to proteins in liver cells $and renal tubules# causing necrosis. Tr at$ nt : If the patient is brought early, vomiting should be induced or gastric lavage done. Activated charcoal is given orally or through the tube to prevent further absorption. 5ther supportive measure, as needed, should be taken. Sp ci#ic : N7acetylcysteine "-9 mg > kg should be infused i.v. over "- min, followed by the same dose i.v. over the ne*t %9 hours. Alternatively, ,- mg > kg may be given orally every / 0 2 hours for % 0 days. U! ! : is one of the most commonly used Jover the counter3 analgesic for headache, musculoskeletal pain, dysmenorrhoea etc. @sed as antipyretic. It does not have significant drug interactions. Do! : 9.-7" g T'& I infants -9 mg I children " 0 %-N?O*A?OCIN- D-RI:ATI:- : N #opa$ : Becently introduced nonopioid analgesic which does not inhibit P8 synthesis. In traumatic and postoperative pain, it acts rapidly with an efficacy approaching morphine, yet has no opioid actions. <avourable results have been obtained in short lasting musculoskeletal pain not responding to other nonopioid analgesics. years +9 0 "29 mg, / 0 + years %/9 0 %9 mg, . 0 "% years 99 0 299 mg CROCIN9 ,-TACIN9 .ARCIN.

Nefopam produces anticholinergic $dry mouth, urinary retention, blurred vision and sympathomimetic $tachycardia, nervousness# side effects, and nausea is often dose limiting. It is contraindicated in epileptics. Do! : 9 0 29 mg T'& oral, %9 mg i.m. 2 hourly. N-FO,A*. Choic o# Non!t roidal anti"in#la$$atory dr'g : ". Dild of moderate pain with little inflammation 0 paracetamol or low dose ibuprofen. %. Acute musculoskeletal, osteoarthritic, injury associated inflammation 0 a propionic acid derivative, diclofenac or piro*icam. . Postoperative or other acute but short lasting painful conditions with minimal inflammation 0 ketorolac, nefopam. /. ;*acerbation of rheumatoid arthritis, ankylosing spondylitis, acute gout, actue rheumatic fever 0 high dose aspirin, indomethacin, napro*en, piro*icam. -. Patients with history of asthma or anaphylactoid reactions to aspirin > other N&AI's 0 nimesulide. 2. 4ombination of two or more N&AI's is not superior to single agents. It at all used, combination therapy should be limited to short periods. SU,,ARY OF S-L-CT-D NSAID DRU( INT-RACTIONS Dr'g Anticoagulants A4; inhibitors )eta blockers 4yclosporine 'igo*in 'ipyridamole :ydantoins =ithium =oop diuretics Dethotre*ate Penillamine &ympathomimetics Thia1ide diuretics .o!!i&l ## ct Increase in prothrombin time or bleeding with anticoagulants $e.g., coumarins# Beduced antihypertensive effectiveness of captopril $especially indomethacin# Beduced antihypertensive effects of beta blockers $e.g.

propranolol, atenolol, pindolol# Increased risk of nephroto*icity Increase in serum digo*in levels

$especially ibuprofen,

indomethacin# Increased water retention $especially indomethacin# Increased serum levels of phenytoin Increased serum levels of lithium Beduced effectiveness of loop diuretics $e.g., furosemide, bumetanide# Increased risk of to*icity $e.g., stomatitis, bone marrow suppression# Increased bioavailability $especially indomethacin# Increased blood pressure $especially indomethacin phenylpropanolamine# Beduced antihypertensive effectivnes.

with

S'gg !t d analg !ic! a#t r c rtain ndodontic! proc d'r ! or condition!: .roc d'r D condition 4anal deberidement Initial choic Aspirin, tylonol, or N&AI' I# $or n d d Analgesic with ">% codeine Analgesic with "g codeine g

4anal 'ebridement where Analgesic with F g codeine considerable overinstrumentation occurred. 4anal filling has where Analgesic with F g codeine

Analgesic with " g codeine

overfilling has occurred and periapical tissue is normal Boot amputation without Nothing flap Periapical or amputational A&A, Tylenol, or N&AI' surgery trauma ;*tensive with minimal with Gicodin or =ortab "9>-99 'emerol, percocet Toradol, Gicodin, or or Percodan or A&A, Tylenol, or N&AI' Analgesic with F g codeine

surgery

considerable trauma 4all after office hours with Analgesics with "g codeine moderate pain 4all after office hours with Gicodin or =ortab "9>-99 severe pain .ain $agnag $ nt !trat gi ! in)ol) ! 1DE!

vicodien ;& 'emerol, Percodan percocet

7 '7'iagnosis 0 appropriate diagnosis of pain, how and where it occurs. 7 ' 0definite treatment 0 to reduce pain 7 ' drugs 7 to control pain. ". 'iagnosis %. 'efinitive dental treatment a# Pulpotomy, pulpectomy b# ;*traction c# Incision for drainage . 'rugs a# Pretreat with N&AI's or acefaminophen when appropriate b# Prescribe by the clock rather than as necessary. c# =ong acting =A when indicated

d# <le*ible prescription plan. Fl ;i&l analg !ic pr !cription !trat gy : A <le*ible analgesic prescription strategy based on research has been developed. O&F cti) to o&tain $a;i$al analg !ia and $ini$al !id ## ct! : Thus a fle*ible pain management plan selected optimal analgesic based upon the patients medical history, level of pain, presence of risk factors for post treatment pain. The non7narcotic component of a combination drug produces greater analgesia with fewer side effects than the opioid component. Thus analgesia can be ma*imi1ed with fewer side effects by using the strategy of first prescribing the most effective dose of a non7narcotic analgesic. Non7narcotic drugs have a ceiling in their dose7response curve. Thus after a ma*imally effective dose is ingested, additional amounts of same drug will not provide a pain controlimplications i.e. patients with proportionate analgesic effect. This <le*ible has some clinical endodontic pain should be asked about how much pain they have $scale of "7"9# and Aspirin like drugs indicated Aspirin like drugs contraindicated about recent history of analgesic use, this will guide in selection of an appropriate analgesic treatment plan. Ibuprofen %99mg N&AI'& $above ma*. effective dose# or N&AI' A acetaminophen Ibuprofen /99mg > / hourly and eMuivalent of acetaminophen 299 > codeine 29 mg every /th hr. N&AI' $ma*. dose# O acetaminophen > o*ycodone "9mg combination. Acetaminophen 2997"999mg Acetaminophen 2997"999mg with eMuivalent of codine 0 29mg.

Acetaminophen "999mg with eMuivalent of o*ycodone "9mg

This plan is divided into % columns for patients who can take N&AI's and for patients who cannot $eg. Those with active ulcers, ulcerative colitis or asthma or those with a potential interaction with certain concomitant drug# each column is then divided into categories based on analgesic recommendations based on level of pain. The overall strategy is to first obtain the best analgesia as a result of the use of the non7 narcotic drug and then to aid narcotic drug when needed for additional pain control. This plan ma*imi1es the analgesic effect and minimi1es side effects. N&AI's alone is sufficient for patients who can tolerate them because of low incidence of post treatment pain and slight to moderate pain. Thus a prescription of N&AI's such as Ibuprofen 299mg>2 hrly is optimal or patients who cannot tolerate it then "999mg of acetaminophen. Patients with moderate to severe pain adeMuate relief with single drug approach not possible. <or these patients % general analgesic approaches. "# %# Ad)anc ! : S l cti) CO* + inhi&itor! ! 4eleco*ib, rofeco*ib, valdeco*ib, etorico*ib, melo*icam, diisopropyl flurophosphate. Action ! Inhibits conversion of arachidonic acid to prostaglandins $4567%#. :ave no effect on prostaglandin formation that mediate normal haemostasis in 8IT, kidney and platelet under control of 4567". C l co;i& p G 9 l G Do! ! 5steoarthritis 0 %99mg >day 5' on "99 mg )', Bheumatoid arthritis 7 %99mg >day 5' on "99 mg )' 4ommerical names ! Ul &r ;9 c li&9 c l#a!t9 'lact )anned 0 Kuly %99" 0 causes 4G& troubles and precipitates myocardial infarction. Ro# co;i& p G 9 l G Do! /+.3 $g OD >$a;i$'m dose %-mg# 4ommercial name, Ro##9 Ro#aday. : :io;;9 Doli& ,D9 do&oro## )anned 0 &ept. %99/ 0 4G& risks and potential life threatening 8" bleeding. )eing reviewed to be in market again. N&AI' A acetaminophen 0 opiod combination $all are analgesics so additive effect <i*ed drug combination of ibuprofen %99mg A hydrocodone ,.- mg. $effective for pain of inflammatory migin#

:ald co;i&! : 'ose 0 "9 0%9 mg 5' 4ommercial name ! )al d9 )al'! 9 :o)th9 % ;tra )anned 0 April , %99-. 7 Potential life threatening skin reactions 0 &teven johnson syndrome, to*ic epidermal necrolysis, erythema multiformae. Oth r dr'g! &ann d &y FDA : 7 7 7 7 7 7 7 7 )eno*aprofen Phynylbuta1one 5*yphenbuta1one Naprofen Piro*icam All N&AI'3s are not at risk =ow doses to be prescribed for short term =abel showing its adverse effects with recommendation for short term use.

<'A announcement

Concl'!ion : People say in life nothing is constant but one thing that is constant and everybody can vouch for it, is the ever increasing population of ours with this increase there is also an e*ponential increase in the number of health professionals too. &o where does one stand with the perspective of drug therapy. It is not only important to know what to give, that anybody can do but where and when to give and how much and for how long to give so as to provide ma*imum beneficial effects and minimum side effects. only this makes all the difference between a Muack and a doctor.

Beferences ! "# ;ffective use of rofeco*ib in comparison to ibuprofen in post endodontic pain.
K5;. Kan %99 , Gol. %., No. ", pg. 2%72/. %# ;valuation of melo*icam $co*7% inhibitor# for management of post operative endodontic pain 0 A double blind placebo controlled study. K5;, 5ct 9 , Gol. %., No. "9, Pg. 2 /72 ,t # The efficacy of pain control following nonsurgical root canal treatment using ibuprofen in a combination of ibuprofen and acetaminophen in a randomi1ed, double7blind, placebo controlled study. I;K, %99/, Gol. ,, Pg. - "7-/".