2. NSAIDs stands Non-Steroidal Anti-Inflammatory
Drugs.
NSAIDs are a class of drugs that provides analgesic
and antipyretic effect & in higher doses anti-
inflammatory effects.
NSAIDs are medications other than corticosteroids
that relieve pain, swelling , stiffness and
inflammation.
4. COX is enzyme responsible for biosynthesis of various
prostaglandins
There are two well recognized isoforms COX called COX-I
and COX-II
COX-I is constitutive found in most tissues such as blood
vessels, stomach and kidneys
PGS have important physiological role in most tissues
COX-II is induced during inflammation by cytokines and
endotoxins and is responsible for the production of prostanoid
mediators of inflammation
Aspirin and most of non steroidal ant inflammatory drugs
inhibit both COX-I and COX-II isoforms thereby decrease PG
and Thromboxane synthesis
The anti-inflammatory effect of NSAIDs is mainly due to
inhibition of COX-II
Aspirin causes irreversible inhibition of COX activity. Rest of
the NSAIDs cause reversible inhibition of enzyme.
5. PGE2 and PGI2 are important prostaglandins involved in
pain. Inhibition of this enzyme produce analgesic effect.
Inhibition of production of prostaglandins induced by
interlukin-1 (IL-1) and interlukin-6 (IL-6) in the
hypothalamus and the resetting of the thermoregulatory
system, leading to vasodilatation and increased heat loss.
6. Aspirin is prototype drug
Salicylates are used to treat rheumatoid arthritis, juvenile
arthritis, and osteoarthritis as well s other inflammatory
disorders. 5-aimino salicylates can be used to treat Crohn
disease.
NSAIDS are mainly used for relieving musculoskeletal
pain and pain associated with inflammation or tissue
damage
Analgesic effect is mainly due to peripheral inhibition of
PGS production
They also increase pain threshold by acting as sub
cortical site
These drugs relieves pain without causing sedation
tolerance or drug dependence
7. The thromboregulatory centre is situated in hypothalamus
Fever occurs when there is disturbance in hypothalamic
thermostat
NSAIDS reset the hypothalamic thermostat and reduce
the elevated body temperature during fever
They promote heat loss by causing cutaneous
vasodilatation and sweating
They do not effect normal body temperature
The antipyretic effect is mainly due to inhibition of PGS in
hypothalamus
8. Anti -inflammatory effect is seen at high doses(aspirin 4-6
g/day in divided doses )
These drugs produce only symptomatic relief
They suppress sign and symptoms of inflammation such as
pain , tenderness swelling vasodilatation and leukocyte
infiltration but they do not effect the progression underlying
disease
The inflammatory action of NSAIDS is mainly due to
inhibition of prostaglandins synthesis at the site of injury
They also affect other mediators of inflammation bradykinin ,
histamine , serotonin and thus inhibit granulocyte adherence
to the damaged vasculature
NSAIDS also cause modulation of t cell function stabilization
of lysosomal membrane and inhibition of chemo taxis.
9. Aspirin in low doses (50-325 mg ) irreversible inhibits
TXA-II synthesis and produces antipalatelet effect which
last 8-10 days i.e. the life time of platelets
Aspirin in high doses 2-3 g/day inhibits both PGI 2 and
TXA-II synthesis.
In therapeutic doses salicylates causes respiratory
alkalosis
In toxic doses the respiratory centre is depressed and can
lead to respiratory alkalosis
In toxic doses the respiratory centre is depressed and can
lead to respiratory acidosis
10. Irritates gastric mucosa and produce nausea vomiting and
dyspepsia
The salicylic acid formed from aspirin also contributes to
these effect
Aspirin also stimulates CTZ and produce vomiting
Prolonged use of aspirin and other NSAIDS causes Na
and water retention
They may precipitate CCF in patients with low cardiac
reserve
They may also compromise the effect of antihypertensive
drugs
11. Inhibit PG synthesis
Ibuprofen and all its congeners are better tolerated than
aspirin. Gastric erosion and occult blood loss are rare.
Rashes, itching and other hypersensitivity phenomena are
infrequent. However, these drugs precipitate aspirin-
induced asthma.
Ibuprofen is used as a simple analgesic and antipyretic in
the same wav as low dose of aspirin.
Dose of ibuprofen is 200- 400 mg, ketoprofen 50-100 mg
12. Potent anti-inflammatory drug with prompt antipyretic
action.
Highly potent inhibitor of PG synthesis and suppress
neutrophil.
Well absorbed orally; 90% protein bind nature,
metabolized by liver and excreted by kidney; plasma t1/2 is
2-5 hours
ADR: high incidence of (up to 50%) GIT and CNS side
effects. Increase bleeding due to decrease platelet
aggregability.
Use: arthropathies, psoriatic arthritis and acute gout
Dose: 25 mg cap, 75 mg cap, 1% eye drop
13. Potent analgesic but moderate anti-inflammatory agent
Efficacy is similar to morphine; inhibits PG synthesis
Rapidly absorbed; 60% protein bind nature, metabolized
by liver (glucuronidation); plasma t1/2 is 5-7 hours
ADR: nausea, abdominal pain, loose stools, pain in
injection site.
Use: used in postoperative (concurrently with morphine);
continuous use for more than 5 days is not recommended.
Topical preparation used for non-infective ocular
conditions.
Dose: 10 mg tab, 30 mg inj. 0.5% eye drops
14. An analgesic-antipyretic-anti- inflammatory drug
Inhibits PG and some what COX-2 selective
Well absorbed orally, 99% protein bound, metabolized and
excreted through urine and bile, plasma t1/2 is approx. 2
hr.
ADR: mild ADRs. Epigastric pain, nausea, headache,
dizziness, rashes. Diclofenac can increase the risk of heart
ach and stroke. Kidney damage is rare.
Use: most extensively used NSAIDs. Rheumatoid, and
osteo-arthritis, ankylosing spondylitis, renal colic, post-
traumatic and post-operative inflammatory condition.
Dose: 50 mg entrecoted tab, 100 mg SR, 1% topical
ointment, 1% eye drops.
15. Selective COX-2 inhibitor
Its exerts with anti-inflammatory, analgesic and
antipyretic actions with low ulcerogenic potential.
ADR: Tolerability of celecoxib is better than traditional
NSAIDs. Still abdominal pain, dyspepsia and mild
diarrhea are common side effects.
Slow absorbed, 97% plasma protein bound and
metabolized primarily by CYP2C9 with t1/2 of approx. 10
hr.
Dose: 100 and 200 mg cap.
16. Central analgesics, Paracetamol has negligible anti-
inflammatory action.
Poor inhibitor of PG synthesis and more active on COX
in brain.
PK: well absorbed orally, only about 1/4th is protein
bound in plasma and it is uniformly distributed in the
body. Metabolism occurs mainly by conjugation with
glucuronic acid and sulfate; conjugates are excreted
rapidly in urine. Plasma half life is 2-3 hr. Effects after
an oral dose last for 3-5 hr.
ADR: Safe and well tolerated. Nausea and rashes occur
occasionally. Leukopenia is rare.
17. Antipyretic: reduce body temperature during fever
Analgesic: to relieve headache, toothache, myelgia,
dysmenorrhoea
Preferred analgesic and antipyretic in patients with peptic
ulcer hemophilia, bronchial asthma and children
Skin rashes, Nausea, Hepatotoxicity, Nephrotoxicity
Acute Paracetamol Poisoning
Hepatotoxicity: Nausea, vomiting, diarrhea, abdominal
pain, hypotension, hypoprothrombinemia coma, death
18. Toxic metabolite is detoxified by conjugation with
glutathione and gets eliminated
High doses of paracetamol causes depletion of
glutathione levels
In absence of glutathione toxic metabolites binds with
protein in liver ,kidney and cause necrosis
Alcoholics and premature infants are more prone to
hepatotoxicity
Activated charcoal is administered to decrease the
absorption of paracetamol from gut.
Charcoal heamoperfusion is effective in severe liver failure
Hemodialysis is required in cases with acute renal failure
19. Useful in chronic and dull aching pains
No advantages over other NSAIDs
Weaker analgesic than aspirin
Adverse reactions include gastric upset, diarrhoea,
dizziness, headache, skin rashes, hemolytic anemia
Dose is 500mg 2-3 times a day
Used in Dysmenorrhoea
20. Structurally different from other NSAIDs
Given orally, well absorbed, has long t1/2 (38-45hrs) and
that permits once-daily administration.
The parent drug as well as its metabolites are renally
excreted in the urine.
Commonly causes GI and CNS disturbances
Has been used to treat rheumatoid arthritis, ankylosing
spondylitis, osteoarthritis and acute gout
21. It is indicated for treatment of rheumatoid arthritis and
osteoarthritis.
It is associated with a low incidence of adverse effects.
Nabumetone is metabolized by the liver to an active
metabolite that displays anti inflammatory, antipyretic
and analgesic activities.
Cautious use of this agents patients with hepatic
impairment is warrented.
The dose should be adjusted in those with creatinine
clearance of less than 50ml/min
