NONSTEROIDAL

ANTIINFLAMMATORY DRUGS

Dr Debasis Sahoo
1st Yr pg Anaesthesia
 Nonsteroidal Antiinflammatory
Drug(NSAIDs)
The NSAIDs are agents that differ in their antipyretic,
analgesic, and anti-inflammatory activities.

In contrast to the opioid analgesics :

Relieve pain without interacting with opioid receptors.
Reduce elevated body temperature (antipyretic effect).
Possess anti-inflammatory property
Have antiplatelet activity to varying degrees.
Do not cause sedation and sleep
Are non-addicting.
 Classification of NSAIDS
A. Nonselective COX inhibitors (traditional NSAIDs)
1. Salicylates: Aspirin.
2. Propionic acid derivatives: Ibuprofen,Naproxen, Ketoprofen,
Flurbiprofen.
3. Fenamate: Mephenamic acid.
4. Enolic acid derivatives: Piroxicam, Tenoxicam.
5. Acetic acid derivatives: Ketorolac,Indomethacin, Nabumetone
6. Pyrazolone derivatives: Phenylbutazone,Oxyphenbutazone.
B. Preferential COX-2 inhibitors
Nimesulide
Diclofenac
Aceclofenac,
Meloxicam
Etodolac
 C. Selective COX-2 inhibitors
Celecoxib
Etoricoxib
Parecoxib
D. Analgesic-antipyretics with poor antiinflammatory action
1. Paraaminophenol derivative: Paracetamol(Acetaminophen).
2. Benzoxazocine derivative: Nefopam
Mechanism Of Action
COX-1 COX-2 COX-3

Constitutive Inducible Recently isolated

House keeping Participate in from cerebral cortex
gastro protection inflamation Involved in pain
Constituive in brain perception & fever
& kidney Not invoved in
Procarcinogenic inflamation
Paracetamol targets
cox-3
 THERAPEUTIC ACTIONS OF NSAIDS-
ANTI-INFLAMMATORY EFFECTS
corresponds to potency to inhibit COX.
Inhibition of COX does not depress mediators like LTs, PAF,
cytokines.
So only suppress the signs and symptoms of inflammation, little
action on underlying chronic disease .
ANTIPYRETIC EFFECTS
Infection or injury

release of IL-1. from macrophages.

produces PG-E in hypothalamus that temperature set point.

NSAIDs inhibit PG production in hypothalamus &es fever .

 ANALGESIC EFFECTS
PGs induce hyperalgesia by affecting the transducing property of
free nerve endings .
NSAIDs block the pain sensitizing mechanism induced by
bradykinin, TNF, interleukins (ILs)etc by inhibiting COX-2. This
constitutes the peripheral component of the analgesic action of
NSAIDs.
the central component of analgesic action by inhibiting PG
synthesis in the spinal dorsal horn neurones as well as in brain.
 Antiplatelet aggregatory
NSAIDs inhibit synthesis of both proaggregatory (TXA2) and
antiaggregatory (PGI2) prostanoids,

but effect on platelet TXA2 (COX-1 generated) predominates

bleeding time is prolonged.

Dysmenorrhoea
level of PGs in menstrual flow and PGF2 metabolite in
circulation are raised in dysmenorrhoeic women.
Basis of usefulness of Nsaids in dysmenorrhea.
 NSAIDs lower uterine PG levelsafford excellent relief in 6070%
Symptoms of headache, muscle ache and nausea also relieved.
Excess flow may be normalized.
Ductus arteriosus closure
During foetal circulation ductus arteriosus is kept patent by local
elaboration of PGE2 by COX-2.
Unknown mechanisms switch off this synthesis at birth and the
ductus closes.
When this fails, indomethacin or aspirin used for closure by
inhibiting PG production.
 Parturition
Sudden spurt of PG synthesis by uterus occurs just before labour
which trigger labour .
So NSAIDs have the potential to delay labour.
UNWANTED EFFECTS
Gastric mucosal damage
Adverse gastrointestinal (GI) events are the commonest
unwanted effects of the NSAIDs.
result from inhibition of gastric COX-1, which synthesises
prostaglandins that normally inhibit acid secretion and protect the
mucosa.
NSAIDs should be taken with food .
When used in patients with a high risk for GI events, proton
pump inhibitors or misoprostol should be used concomitantly
 Renal effects
NSAIDs produce renal effects by at least 3 mechanisms:
1-COX-1 dependent impairment of renal blood flow and
reduction of g.f.r. can worsen rena insufficiency.
2-Juxtaglomerular COX-2 (probably COX-1 also) dependent Na+
and water retention.
3-Ability to cause papillary necrosis on habitual intake.
Renal effects of NSAIDs become significant

in those with CHF, hypovolaemia, hepatic cirrhosis, renal disease

and in patients receiving diuretics or antihypertensives.
 .
Analgesic nephropathy-
after years of heavy ingestion of analgesics.
Regular use of combinations of NSAIDs & repeated UTI es the risk
of analgesic nephropathy.
There occurs papillary necrosis, tubular atrophy &renal fibrosis.
Urine concentrating ability is lost and the kidneys shrink.
Anaphylactoid reactions
precipitates asthma, angioneurotic swellings, urticaria or rhinitis .
Inhibition of COX with consequent diversion of arachidonic acid to
LTs may be involved.
 Adverse effects of NSAIDs
Gastrointestinal CNS
Nausea, anorexia, Headache, mental confusion,
gastric irritation, erosions, vertigo, behavioural
peptic ulceration, gastric bleeding disturbances, seizure
esophagitis precipitation
Renal Haematological
Na+ and water retention, Bleeding, thrombocytopenia,
chronic renal failure, haemolytic anaemia,
agranulocytosis
nephropathy, papillary necrosis (rare)
Others
CVS Asthma exacerbation, rhinitis,
Rise in BP, nasal polyposis, skin
risk of myocardial infarction (especially rashes, pruritus, angioedema
with COX-2 inhibitors)
Hepatic
Raised transaminases,
hepatic failure (rare)
 Pharmacokinetics-
NSAIDs are highly bound to plasma proteins, specifically to
albumin (>90%), and therefore only a small portion of the
circulating drug in plasma exists in the unbound
(pharmacologically active) form.
The V of NSAIDs is low i.e 0.1 to 0.3 L/kg,
Most NSAIDs are weak acids with pKa less than 6
But the coxibs are nonacidic, which may play a role in the
favorable tolerability profile.
Absorption-
Most NSAIDs are administered enterally .
rapidly and completely absorbed from the (GI) tract
food tends to delay absorption
 Distribution-
weakly acidic, highly PPB(albumin& lipophilic)
Due to low pH ,NSAIDs are ionized at physiologic pHs.
In areas with acidic extracellular pH, NSAIDs may accumulate
(inflamed tissue, GI tract, kidneys)
The high protein binding of the NSAIDs has relevance in the state
of hypoalbuminemia ,elderly, malnourished.

unbound NSAIDs conc. in plasmatoxicity.

NSAIDs compete with highly PPB drugs such as warfarin;
possibility of bleeding ed. .
Biotransformation & excretion
Most COX inhibitors undergo hepatic biotransformation.
Nearly all COX inhibitors are excreted in urine.
 DRUG INTERACTION WITH NSAIDS
Pharmacodynamic
Diuretics : Diuresis
blocker : Antihypertensive effect
ACE inhibitors : Antihypertensive effect
Anticoagulants : risk of G.I. bleed
Sulfonylureas : risk of Hypoglycaemia
Alcohol : Risk of G.I. bleed
Cyclosporine : Nephrotoxicity
Corticosteroids : Risk of G.I. bleed
Selective serotonin reuptake inhibitors : Risk of G.I. bleeding.
 Pharmacokinetico
Oral anticoagulants Metabolism inhibited
Sulfonylureas
Pharinetic &competition for plasma
Phenytoin protein binding
Valproate
Digoxin Methotrexate

Digoxin Renal
Lithium excretion of
Aminoglycosides interacting drug
Methotrexate
 ASPIRIN(ASA)
Aspirin is acetylsalicylic acid.
converted in the body to salicylic acid responsible for most of the actions
MOA-
By irreversible inhibition of COX through acetylation of serine hydroxyl group.
How Long until It Works-
A single dose inhibits platelet aggregation for the life platelet (710 days).
In pain, effective within 12 hours.
Usual Dose Range Aspirin
MI, TIA, or IS prevention: 501300 mg/day
Pain: 3251000 mg per dose.
Dosage Forms Aspirin
Chewable tablets:
Tablets:
Gum tablets:
Enteric-coated:
Extended- or controlled-release
Suppositories:
 How to Dose Aspirin
Give once daily for prevention of vascular events. For pain, take 325 1000 mg
every 46 hours as needed up to a maximum of 4000 mg per 24 hours.
Pharmacokinetics
Aspirin half-life is 20 minutes.
Over 99% protein binding.
Hepatic metabolism
renal excretion.

Actions are dose-dependent:

- Antiplatelet aggregation. Low dose,
- Analgesia and antipyresis. Moderate dose
- Antiinjlammatory. High doses
- Uric acid elimination
Low to moderate doses:tubular secretion hyperuricemia
High doses: tubular reabsorption uricosuria
 Drug Interactions-
Alcohol - GI ulceration , bleeding time.
Carbonic anhydrase inhibitors(acetazolamide)-salicylate intoxication,
heparin or oral anticoagulants- bleeding
Aspirin es effect of loop diuretics ,spironolactone, blockers, ACE
inhibitors.
may cause unexpected hypotension after treatment with nitroglycerin.
es pharmacologic effects of valproate(displacing from binding site)
Antiacids and urinary alkalinizers may decrease drug effect.
Corticosteroids may clearance and decrease serum levels of aspirin.
produce hypoglycemia when used with insulin or sulfonylurias in diabetes.
es drug levels of methotrexate.
es uricosuric effects of probenecid and sulfinpyrazone.
 Commonly Prescribed For
To reduce risk of (MI), (TIA), or ischemic stroke (IS) due to fibrin platelet
emboli
Angina (unstable or stable)
Revascularization procedures:
(CABG), angioplasty, and carotid endarterectomy
Analgesic for mildmoderate pain for relief of headache, muscleaches and
pains, toothache, arthritis, menstrual pain
Fever
Do Not Use Aspirin
Known hypersensitivity to salicylates, acute asthma or hay fever,
severe anemia or blood coagulation defects,
children or teenagers ( 12 yrs)with chickenpox or influenza symptoms.
crosses the placenta & associated with anemia, ante or postpartum
hemorrhage, prolonged gestation and labor, and constriction of ductus
arteriosus. Do not use, especially in 3rd trimester
 Special precautions-
use of aspirin in children influenza or chickenpox may be associated with Reye's
syndrome.
Symptoms include vomiting and lethargy delirium or coma
Tinnitus or dizziness are early symptoms of aspirin toxicity.
aspirin-intolerance-
Within 3 hours of ingestion of aspirin pts develop bronchoconstriction
accompanied by rhinorrhea, conjunctival irritation, and scarlet flush.
In severe cases, a single therapeutic dose can provoke violent bronchospasm,
loss of consciousness, and respiratory arrest.
In order to diagnose AIA, oral, inhaled, nasal or intravenous aspirin challenge
tests are performed where facilities available.
Aspirin resistance-
refers to suppression of thromboxane A(2) production by aspirin and
associated with risk of adverse cardiovascular events. causes include poor
compliance, drug interaction, inadequate aspirin dose, increase turnover of
platelets, genetic polymorphisms of cyclo-oxygenase-1, and upregulation of
alternate (non-platelet) pathways of thromboxane production
 Multiple assays are now available to measure the effect of a given
dose of aspirin on platelet function.
These include standard platelet aggregometry and tests measuring
the effect on COX-1 by measuring thromboxane metabolites.
The ACCPs guidelines suggest in patients who require temporary
interruption , discontinue aspirin 7 to 10 days before surgery.
patients who have had temporary interruption of aspirin therapy
because of surgery, resuming aspirin approximately 24 hours (or
the next morning) after surgery when there is adequate
hemostasis is recommended.
In high risk group pts(with unstable angina or recent MI) requiring
urgent CABG aspirin should be continued until the time of
surgery.
Aspirin plus Clopidogrel used as Secondary Prevention after Stroke
or Transient Ischemic Attack.
 Other nonselective NSAIDs
Indomethacin-
From analgesic& antipyretic point it is not preferred due to
severe S/E
But used as antipyretic in hodgkins disease
Highly effective in ophthalmic inflammation.
T/t with indomethacin & spironolactone improve the symptoms
of Bartters syndrome.
ADR- thrombocytopenia, neutropenia, aplastic
anaemia,precipitation of asthma,causes severe frontal
headache(analgesic causing pain)
Mefenamic acid-
It possesses PG receptor antagonistic & phospolipase A2
inhibitory activity.
Very useful in dysmenorrhea
Diarrhea is MC S/E.
 Ketorolac-
Analgesic action anti inflammatory activity
Inhibits platelet aggregation & PG synthesis.
Used in postoperative pain as an alternative to opioid.
Topically for ocular inflammation& allergic conjuctivitis(as eye drops)
It can be used by oral, i.m ,i.v route.
Pain at site of injection,renal toxicity.
Ketorolac promethamine is available as nasal spray.
administered as spray in each nostril (15.75 mg) 6-8 hrly(not more than
4 doses per day)
Course longer than 5 days not recommended.
Piroxicam-
Better tolerated than aspirin or indomethacin.
Additional action inhibits activation of neutrophils
inhibits synthesis of proteoglycans& collagen
es production of Ig M rheumatoid factor
Has long t (38-50 hr) due to enterohepatic cycling ,so used once a day
 DICLOFENAC-
It is a phenylacetic acid derivative.
Presentation& dosage forms-
Suppository-12.5mg&25 mg.
Arthrotec 50: 50 mg Diclofenac + Misoprostol 200 g
Arthrotec 75: 75 mg Diclofenac + Misoprostol 200 g
Tablet, oral, as potassium: 50 mg
enteric coated delayed release Tablet (dic. Sodium): 25 mg, 50 mg,
75 mg
extended release tablet (dic.sodium): 100 mg
Also available 75 mg/3 ml inj, 0.1% eye drops
Uses-
Postoperative pain,injury like bursitis,tendonitis.
primary dysmenorrhea.(50 mg 8hrly)
Acute and chronic treatment of rheumatoid
arthritis,osteoarthritis,ankylosing spondylitis.
 Treatment of acute migraine with or without aura
Postoperative pain/posttraumatic pain
MOA-
Inhibits PG synthesis and is somewhat COX-2 selective.
antiplatelet action is not appreciable due to sparing of COX-1.
.PHARMACOKINETICS-
well absorbed orally.
99% protein bound,
metabolized by CYP2C .
excreted both in urine and bile.
plasma t is 1~2 hours.
Good tissue penetrability i.e in synovial fluid
 ADR-
Elevation in hepatic transaminases (usually borderline)
Edema
Dizziness, headache
Pruritus, rash
Fluid retention
Abdominal distension, abdominal pain, constipation,
diarrhea,
dyspepsia, flatulence, GI perforation, heartburn, nausea,
peptic ulcer/GI bleed, vomiting
Anemia, bleeding time increased
Tinnitus
Renal function abnormal
Can increase the risk of heart attack and stroke
 Pharmacokinetics
Onset of action potassium saltis more rapid than the sodium salt.
Distribution: ~1.4 L/kg
Protein binding: >99%, primarily to albumin
Metabolism: hepatic; undergoes first-pass metabolism.
Bioavailability: 55%
Half-life elimination: ~2 hours
Time to peak, serum conc: ~0.25 hours
Excretion: urine ~65%; feces ~35%
Drug Interactions
alcohol, bisphosphonates, corticosteroids, anticoagulants,&other
NSAIDs- GI bleeding risk.
Cyclosporine and NSAIDs nephrotoxicity
 Aceclofenac-
A moderately COX-2 selective congener of diclofenac.
Enhancement of glycosaminoglycan synthesis
chondroprotective property. Dose: 100 mg BD
Nimesulide-
Partially selective inhibitor of COX.
Causes hepatic damage& agranulocytosis.
Used for rheumatoid arthritis in adults not responding to other
Nsaids
Recently banned in india for children 12 yrs.
Etodolac-
A racemic acetic acid derivative with parially selective COX-2
activity
Used in dose 200-300mg 4times daily.
S-Etodolac has potency twice that of racemate .
S-Etodolac has greater concentrations in synovial fluid than plasma
 SELECTIVE COX-2 INHIBITORS (Coxibs)

Advantages of coxibs- Disadvantages

Less G.I. side effects incidence of thrombosis(MI
Not precipitate asthma &stroke.
No antiplatelet action
No bleeding

Currently, 3 coxibs Celecoxib, Etoricoxib and Parecoxib are

available in India.
Rofecoxib & Valdecoxib were for increasing cardiovascular risk.
Celecoxib- dose ;100200 mg BD
Celecoxib, Rofecoxib & Valdecoxib are sulphonamide derivative
rash & hypersensivity.
May cause HTN,thrombosis,atherogenesis so lowest
possible drug should be used for shortest period of time.
Avoid using it with lithium& fluconazole d/t drug interaction
 Etoricoxib-
Longest acting coxib,used once daily dose.
Monitoring of hepatic function is must during t/t.
Renal insufficiency doesnt affect clearance .
Lumiracoxib-
Plasma t 1-3 hr ,t1/2 in synovial fluid ~ 24 hr
Max. COX-2 selective activity
No gastric injury even at higher dose.
Higher hepatotoxicity among coxibs.
Parecoxib-
Pro drug of valdecoxib
Only coxib available as injection.
Effective analgesic in pre &post operative period when pts cant
take oral drug.
 Propionic acid derivatives-
Ibuprofen
it is the better tolerated drug among propionic acid derivatives, is
costeffective and good substitute for aspirin as an
antiinflammatory agent.
Used in paediatric patients.
Safest& least gastrotoxic among conventional NSAIDS.
Ketoprofen
Among NSAIDs only Ketoprofen inhibits lipooxygenase & COX.
Also have lososomal stabilising activities.
Rare s/e of ketoprofen is aseptic meningitis(in pts with CTD eg.SLE)
Flurbiprofen
is also available as eye drops for eye inflammation.
 Naproxen
Also inhibit leucocyte migration.
Most potent among propionic acid derivatives
All NSAIDs are racemic mixtures except naproxen (present as
single enantiomer)
Fenoprofen
Causes interstitial nephritis
So not used currently.
Nefopam-
does not inhibit PG synthesis
but relieves traumatic, postoperative and shortlasting
musculoskeletal pain.
produces anticholinergic (dry mouth, urinary retention, blurred
vision) and sympathomimetic (tachycardia, nervousness) side
effects.
It is contraindicated in epileptics.
Dose: 3060 mg TDS oral.
 PARACETAMOL(ACETAMINOPHEN)
It is a p-aminophe3nol derivative.
It was first used clinically by Von Mering in 1893.
MOA-
No inhibition of COX in peripheral tissues* and lacks significant
antiinflammatory effects.
Equivalent analgesic and antipyretic activity to ASA due to
inhibition of cyclooxygenases in the CNS.(cox -3 inhibition ?)

In comparision 1.no antiplatelet action

to aspirin 2.not bronchospastic.
3.not implicated in reyes
syndrome
4.gi distress minimal.
5.no effect on uric acid.
 Pharmacokinetics-
well absorbed orally.
only about 1/4th is protein bound in plasma.
Metabolism by conjugation with glucuronic acid and sulfate.
Due to N hydroxylation there is formation of
N-acetyl-p-benzoquinoneimine(NAPQI).
Plasma t is 23 hours,effects of an oral dose last 35 hours.
Onset of action
Oral: within 1 hour
IV: within about 510 minutes
Dosage Forms
Oral: Tablets: 325 mg, 500 mg
Oral:extended relief tablets: 650 mg caplet(for arhritis)
IV-1 gm,PARACETAMOL RECTAL SUPPOSITORY 80, 170 mg.
125 mg/5 ml syrup, 100 mg/ml paed. drops,
pcm with methionine tab also available
 Commonly Prescribed For
Pain
Fever
Postoperative pain
Perineal pain in early postpartumperiod.
Dosing schedule: 3251000 mg every 46 hours; maximum daily
dose 4 g/day.
Adverse effects
paracetamol is safe and well tolerated.
Nausea and rashes occur occasionally.
Acute paracetamol poisoning.
especially in small children who have low hepatic glucuronide
conjugating ability.
If a large dose(> 150 mg/kg or > 10 g in an adult) is taken,serious
toxicity can occur.
 Early manifestations -nausea, vomiting, abdominal pain and liver
tenderness.

After 1218 hours tcentrilobular hepatic necrosis , renal tubular

necrosis, hypoglycaemia ,coma

hepatic failure and death if the plasma levelsare above 200

g/ml at 4 hoursand 30 g/ml at 15 hours.
Mechanism of toxicityt-
N-acetyl-p-benzoquinoneimine(NAPQI) is a highly reactive of
paracetamol detoxified by conjugation with glutathione.
Whena very large dose of paracetamol is taken,glucuronidation
capacity is saturated,
hepatic glutathione is depleted and this metabolite binds
covalently to proteins in liver cells (and renal tubules) causing
necrosis.
 Treatment
If the patient is brought early, vomiting should be induced or
gastric lavage done.
Activated charcoal is given orally or through the tube
Other supportive measures should be taken.
If conc.of pcm above 300mic gm/ml at 4 hr after ingestion&
above 50 mic gm/ml at 12 hr the t/t shuld be by specific antidote
i.e N-acetylcysteine.
150 mg/kg should be infusedi.v. over 15 min,

followed by the same dose i.v. over the next 20 hours.

Oral-140mg/kg followed by 70mg/kg every 4 hr.
Only iv route used in pts20kg.
Effect is most when administered within 8 hr.
 Do Not Use Acetaminophen
Hypersensitivity or anaphylaxis to any acetaminophen-like or
containing agents
In conjunction with alcohol(alcoholism induces CYP2E1 that
metabolises paracetamol to NAPQI.)
Over 4 g/day
In patients with severe liver injury
in premature infants (< 2 kg) for fear of hepatotoxicity
 Choice of NSAIDs
Mild-to-moderate pain,little inflammation: paracetamol or low-
dose ibuprofen.
Postoperative ,acute but shortlasting pain: -ketorolac,
diclofenac or nimesulide.
Exacerbation of rheumatoid arthritis, ankylosing spondylitis,
acute gout, acute rheumatic fever:- naproxen,
piroxicam,indomethacin, high dose aspirin.
Gastric intolerance : a selective COX-2 inhibitor or
paracetamol.
Arthritis patients who are dependent on NSAIDs must
receive concurrent PPI as gastroprotective.
Patients with history of asthma or anaphylactoid reaction to
aspirin/other NSAIDs:nimesulide, COX-2 inhibitor
 Patients with hypertension ,risk factor for stroke-avoid coxibs, a
propionic acid derivative or aspirin may be used
Paediatric patients: only paracetamol, aspirin, ibuprofen and
naproxen .
Elderly patients: use lower dose of the chosen NSAID.
Fast acting drug -suitable for fever, headache and other short
lasting pain,
while longer acting drugs- appropriate for chronic arthritic pain.
Pregnancy: paracetamol is the safest; lowdose aspirin second best.
Hypertensive, diabetic, ischaemic heart disease, epileptic-:
possibility of drug interaction with NSAIDs should be considered
 Anti-inflammatory doses of non-selective NSAID
Name Available as Dose/Frequency
Ibuprofen 200, 400 mg tab 400 600 mg tid
Ketoprofen 50 mg capsules 50 mg tid
Naproxen 250 mg tablets 250500 mg bid
Diclofenac 50 mg tablets 50 mg bid
Indomethacin 25 mg capsules 2550 mg tid
Piroxicam 10, 20 mg capsules 1020 mg od
Plasma half-lives of NSAID
Less than 5 hours
Aspirin, Diclofenac, Ketoprofen, Flurbiprofen,
Indomethacin,.
1030 hours Diflunisal,
Fenoprofen, Naproxen, Sulindac, Nabumetone.
More than 50 hours
Phenylbutazone, Piroxicam, Tenoxicam.
 FUTURE NSAIDS-
GI toxicity, is the MC s/e of NSAIDs.
(NO)-releasing NSAIDs, a recently described class of drugs
generated by adding a nitroxybutyl or a nitrosothiol moiety to the
parent NSAID via a short-chain ester linkage.
nitroxybutyl-NO-NSAIDs have been extensively studied in animals.
In addition to nonselective cyclo-oxygenase (COX) inhibition, they
suppress production of the cytokines interleukin (IL)-1beta, IL-18
and interferon-gamma by causing the S-nitrosilation/inhibition of
caspase-1.
NO-NSAIDs es prostaglandin E2 as well as thromboxane B2
generation.
NO-naproxen was approximately 10-fold more potent than
naproxen ,
 By coupling the ability to inhibit COX-1 with anti-adhesive effect
of NO.

NO-aspirin (acetylsalicylic acid) exerts more potent

antithrombotic action than aspirin.
NO-flurbiprofen has been demonstrated to be devoid of
nephrotoxicity.
MULTIMODAL ANALGESIA
involves the administration of 2 or more analgesic agents by one
or more routes.
act synergistically at different sites in the nervous system, thereby
providing superior analgesia with fewer side effects.
It allows early ambulation, promote better rehabilitation,
accelerate recovery, and reduce the length of hospital stay.
Local anesthetics, acetaminophen, and NSAIDs are the other
treatment options, with opioids being reserved as a rescue drug
only.
 Take Home Message
Before prescribing combination NSAIDs ,think about the possibilty of
analgesic nephropathy.
If one class of NSAID does not cause analgesia, switch to an alternative
class of NSAID.
when one group of NSAID is effective but produces intolerable side
effects, search for another agent in the same class before switching to
another group of NSAID.
Do not take Nsaids as many days you want, eg. ketorolac is not
recommended for 5 days for risk of serious gastrointestinal side
.effects.
Before prescribing NSAIDs consider factors like age of
pt,pregnancy,previous PUD, Concomitant administration of
corticosteroids,antiepileptics,antihypertensive.
Because of doubtful efficacy& high cost, topical NSAIDs should not be a
preffered choice.
The choice of nonselective NSAIDs& COX-2 inhibitor depend upon the
balance between G.I. side effect to that of CV risk.
When used in patients with a high risk for GI events, proton pump
inhibitors should be used concomitantly
Thank you
 NEXT SEMINAR

ANAESTHETIC MANAGEMENT OF
HAEMOGLOBINOPATHIES
Dr Kasturi Nanda