basics of NSAID: non -steroidal anti-inflammatory drugs

1. NSAID: nonsteroidal
anti-inflammatory drugs
Dr. Shrey Bhatia
Jr
Gmc, patiala

2. introduction
• None of them are steroids
• All are analgesic, anti-pyretic and anti-inflammatory ( paracetamol is not
anti-inflammatory)
• Do not produce CNS depression, respiratory depression and don’t cause
drug dependence
• Act by inhibiting prostaglandin synthesis (except nefopam and diacerein)

3. NSAID
NSAID

6. Classification
Non selective
IRREVERSIBLE
COX-inh
• Aspirin
• Sodium salicyclate
• Sulfasalazine
• Osalazine
• methylsalicyclate
Non selective
REVERSIBLE
COX-inh
• Oxyphenbutazone
• Indomethacin
• Ibuprofen
• Ketoprofen
• Naproxen
• Mefenamic acid
• Piroxicam
• Tenoxicam
• Ketorolac
• Diclofenac
• aceclofenac
Weak COX-1<COX-2 +
other modes of anti-
inflammation
• nimesulide
Preferential COX-2 inh
• Meloxicam
• Etodolac
• nabumetone
Selective COX-2 inh
• Rofecoxib
• Valdecoxib
• Etoricoxib
• Parecoxib
• celecoxib
COX-3 inh
• Paracetamol
• metamizol
Donot inhibit
prostaglandins
• Nefopam
• diacerein

7. Non selective IRREVERSIBLE COX- inhibitors
ASPIRIN
Pharmacological actions
ANALGESIA
• Relieves integumental pain associated with inflammation/tissue injury
• Not effective in visceral pain and ischemic pain
• Uses: headache, backache, toothache, myalgia, neuralgia,
dysmenorrhoea, rheumatoid arthritis, cancer pain

8. Non selective IRREVERSIBLE COX- inhibitors
ASPIRIN
Pharmacological actions
ANTI-PYRETIC
• Reduces raised body temperature, does not effect normal body
temperature
• Resets hypothalamic thermostat
• Uses: reducing fever of any origin

9. Non selective IRREVERSIBLE COX- inhibitors
ASPIRIN
Pharmacological actions
ANTI-INFLAMMATORY
• Decreases vasodilatory PGs( PGE2, PGI2) less edema
• Increases resistance of connective tissue mucopolysaccarides to
prevent spread of inflammation
• Uses: osteoarthritis, rheumatoid arthritis, rheumatic fever

10. Non selective IRREVERSIBLE COX- inhibitors
ASPIRIN
Pharmacological actions
INHIBITION OF PLATELET AGGREGATION
Mechanism:
• Thromboxane A2 ( TXA2) – platelet aggregation,
• PGI2– decreases platelet aggregation
• By irreversibely inhibiting COX -1, should decreases both TXA2 and PGI2
• Platelets have no nucleus, life span – 7 days, cannot synthesize COX after
inhibition by aspirin
• Vascular endothelium can regenerate COX after inhibition
• Uses: Aspirin is used at low doses ( 75-100mg) to decrease TXA2
production and inhibition of platelet aggretation; lower risk of re-infaction
post MI, deep vein thrombosis, pulmonary embolism

11. Non selective IRREVERSIBLE COX- inhibitors
ASPIRIN
Pharmacological actions
RELIEF IN DYSMENORRHOEA
• PGE and PGF2α are increased in dysmenorrhoea menstrual cramps
• Aspirin reduces uterine PG levels

12. Non selective IRREVERSIBLE COX- inhibitors
ASPIRIN
Pharmacological actions
CLOSURE OF DUCTUS ARTERIOSUS
• Ductus arteriosus is kept patent by PGE2 and PGI2
• This synthesis is switched off at birth closure of ductus
• Uses: low dose aspirin brings about closure of ductus arteriosus (by
inhibiting PGE2 and PGI2 ) if fails to close at birth

13. Non selective IRREVERSIBLE COX- inhibitors
ASPIRIN
Pharmacological actions
MISC:
• Colon cancer, rectal cancer- chronic use reduces risk
• Pre-eclampsia- by supressing TXA2
• Alzheimer’s disease- lowers risk
• Familial colonic polyposis- supresses polyp formation
• Slow down cataract progression

14. Non selective IRREVERSIBLE COX- inhibitors
ASPIRIN
Adverse effects
GASTRIC MUCOSAL DAMAGE:
• PGE2 and PGI2 inhibit gastric acid secretion, stimulate mucus and
bicarbonate production
• Aspirin decreases PGE2 and PGI2 gastric acid release, no protective
mucus layer gastric mucosal damage

15. Non selective IRREVERSIBLE COX- inhibitors
ASPIRIN
Adverse effects
DISTURB ACID BASE BALANCE
• At 400 ug/ml -500ug/ml : Respiration is stimulated by direct action on
respiratory centre washout CO2  respiratory alkalosis
• At 500 ug/ml -1mg/ml: depression of respiratory center pCO2
increase respiratory acidosis
• at > 1mg/ml: aspirin hydrolized to salicyclic acid, depression of renal
function to remove metabolic acids, derangement of carbohydrate
metabolism  metabolic acidosis

16. Non selective IRREVERSIBLE COX- inhibitors
ASPIRIN
Adverse effects
BLEEDING TENDENCIES
• Decrease prothrombin levels by decreasing proconvertin ( factor V)
HYPERSENSITIVITY
• Diversion of arachidonic acid to lipoxygenase pathway  increase
leukotrienes bronchoconstriction, skin rash, rhinitis, angioneurotic
edema

17. Non selective IRREVERSIBLE COX- inhibitors
ASPIRIN
Adverse effects
EFFECT OF URIC ACID
• < 2g/day: decrease uric acid excretion
• >5g/day: increase uric acid excretion ( not used in gout because high
doses are not tolerated)
RENAL EFFECTS
• Patients with CHF, cirrhosis, renal disease analgesic nephropathy

18. Non selective IRREVERSIBLE COX- inhibitors
ASPIRIN
Adverse effects
REYS’S SYNDROME
• Aspirin intake when children are recovering from febrile viral fever 
reys’s syndrome: liver damage, encephalopathy

19. Non selective IRREVERSIBLE COX- inhibitors
• METHYL SALICYCLATE : used in balms, aka “ oil of wintergreen”
• SALICYLIC ACID: keratolytic agent, treatment of corns and warts
• SULFASALAZINE: treatment of ulcerative colitis, rheumatoid fever
Non selective REVERSIBLE COX- inhibitors
INDOMETHACIN
• immunosuppressive actions
• Use: ankylosing spondylitis, closure of ductus arteriosus
• ADR: more potent GI upset, hallucination, vertigo, confusion ( C/I in
epilepsy and psychiatric cases

20. Non selective REVERSIBLE COX- inhibitors
• IBUPROFEN: ADRs less than aspirin ( 400mg TDS)
• DICLOFENAC: 99% protein bound, moderate potency, moderate GI
upset ( 50mg TDS)
• ACECLOFENAC : same as diclofenac, longer acting ( 100mg BD)
• MEFENAMIC ACID: also PG receptor antagonist action, inhibits
leucoterine, used in dysmenorrhoea ( 250-500mg TDS)
• KETOROLAC: eye drops for seasonal allergic conjunctivitis

21. Weak inh of COX 1 and 2, other mode of anti-
inflammatory actions
NIMESULIDE
• Reduce superoxide generation, free radicals, PAF, metalloproteinase
activity in connective tissues
Preferential COX-2 inh
MELOXICAM, ETODOLAC, NABUMETONE
Longer action, less gi toxicity, no superiority over other NSAID

22. Selective COX-2 inh
CELECOXIB, VALDECOXIB, ETROCOXIB, ROFECOXIB,
PARECOXIB
• COX-2 is induced at the site of inflammation
• Inhibits COX-2 without affecting COX-1 present in GIT and platelet
no GI upset
ADR
• Reduce whole body PGI without affecting TXA2 platelet aggregation
enhanced
• Renal toxicity
USES
• Osteoarthritis, rheumatoid arthritis, dysmenorrhoea, gouty arthritis,
musculoskeletal pain

23. COX-3 inh
PARACETAMOL( acetaminophen)
• COX-3 is involved in pain perception and fever, not in inflammation
• Does affect acid-base balance
• Does not produce gastric mucosal damage
• Does not affect platelet aggregation
USES: mild-mod pain, in patients with peptic ulcer, hemophilila,
bronchial asthma, children with viral fever; dose- 500mg TDS
ADRs
Nausea, skin rash, mild increase in hepatic enzymes

24. Acute PARACETAMOL poisoning
• Children, adults with compromised hepatic function, chornic
alcoholics lower glucuronide conjugation ability
• Major pathway of PCM metabolism: Glucuronide conjugation
• Minor pathway : cyt P450 form toxic metabolite N-acetyl-p-
benzoquinone imine metabolized by glutathione conjugation
• At toxic doses ( 4-5g/day), large amount of toxic metabolite formed
glutathione cannot handle metabolism hepatic and renal cell
necrosis

26. Acute PARACETAMOL poisoning
treatment
• Start within 16 hrs of PCM ingection
• Vomiting induced
• Gastric lavage done
• Activated charcoal given
• Administration of N-acetycysteine ( IV) and methionine : have SH
group like glutathione replenish glutathione

27. DONOT inhibit PGs
NEFOPAM, DIACEREIN
• Used for short lasting musculoskeletal pain not responding to other
NSAID
• Post op pain, cancer , dental pain
• ADR: atropine like ( dry mouth, urinary retention, blurred vision)
• Diacerein- discoloration of urine