1. Pharmacology for Allied health sciences
Nonsteroidal Anti-inflammatory
Drugs and Antipyretic-Analgesics
Dr. S. Parasuraman
Faculty of Pharmacy, AIMST UNV

2. NSAIDs
• They are also called nonnarcotic/ nonopioid analgesics.
• They act primarily on peripheral pain mechanism.
• NSAIDs are used to suppress the symptoms of inflammation
associated with rheumatic disease. Some are also used to
relieve pain (analgesic) and fever (antipyretic).

3. NSAIDs
Nonselective COX inhibitors
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Salicylates: Aspirin.
Propionic acid derivatives: Ibuprofen, Ketoprofen, Flurbiprofen.
Fenamate: Mephenamic acid.
Enolic acid derivatives: piroxicam, Tenoxicam.
Acetic acid derivatives: Ketorolac, Indomethacin.
Pyrazolone derivatives: Phenylbutazone, Oxyphenbutazone.
Preferential COX-2 inhibitors:
• Nimesulide, Diclofenac, Aceclofenac, Meloxicam, Etodolac.
Selective COX-2 inhibitors:
• Celecoxib, Etoricoxib, Parecoxib.
Analgesic-antipyretics with poor antiinfammatory action:
• Paraaminophenol derivative: Paracetamol (Acetaminophen)
• Pyrazolone derivatives: propiphenazone
• Benzoxazocin derivative: Nefopam

4. NSAIDs
Mechanism of action of NSAIDS:
• Anti-inflammatory effect of NSAIDs due to inhibition of that
produce prostaglandin H sysntase (Cyclooxygenase/ COX),
which convert arachidonic acid to Tx and PG. NSAIDs not have
effect on lipoxygenase.

5. NSAIDs
Mechanism of action analgesics:
• PGE2 and PGI2 are important prostaglandins involved in pain.
Inhibition of this enzyme produce analgesic effect.
Mechanism of action antipyretic:
• 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. Therapeutic uses
Inflammation
• NSAIDs are first-drugs used to arrest inflammation
and the accompanying the pain of rheumatic and
nonheumatic diseases, including rheumatoid
arthritis, juvenile arthritis, osteoarthritis, psoriatic
arthritis, ankylosing spondylitis, Reiter syndrome and
dysmenorrhea.
• NSAIDs are don’t reverse the process of rheumatic
diseases rather, they slow destruction of cartilages
and bone and allow patients increased mobility.

7. Salicylates
Aspirin
• Aspirin is acetylsalicylic acid. It is rapidly converted in the
body to salicylic acid which is responsible for its
pharmacological actions.
• Aspirin is a weaker analgesic than morphine (600 mg ~codeine
60 mg)
• The analgesic action is mainly due to prevention of PGmediated sensitization of nerve endings of peripheral nervous
system.
• Aspirin resets the hypothalamic thermostat and rapidly
reduces fever by promoting heat loss (sweating, cutaneous
vasodilatation), but does not decrease heat production.

8. Salicylates
Aspirin (75-350 mg)
• Anti-inflammatory action is exerted by COX inhibition
at high doses (3-6 g/ day or 100 mg/kg/ day).
Aspirin -Therapeutic uses
• 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.
• Salicylic acid is used topically to treat plantar warts,
fungal infections, and corns.

9. Salicylates
• GI effects are most common (nausea, vomiting, diarrhea,
constipation, dyspepsia, epigastric pain, bleeding,
ulceration). Enteric-coated or timed-release preparation
my reduce gastric irritation.
• Hypersensitivity reaction is uncommon (0.3% of
patients), it results rash, bronchospasm, rhinitis, edema,
or an anaphylactic reaction with shock, , which may be
life threatening.
• Decrease glomerular filtration rate (in renal insufficiency
patient).
• Prolog bleeding time
• Salicylates are not recommended during pregnancy they
may cause postpartum hemorrhage.

10. Propionic acid derivatives (Ibuprofen)
• Inhibit PG synthesis
• Adverse effects:
– 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 aspirininduced asthma.
• Use:
– 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
(also inhibit LOX), flurbiprofen 5 mg.

11. Enolic acid derivatives (Piroxicam)
• Long acting potent NSAID with similar anti-inflammatory
action of indomethacin.
• Reversible inhibitor of COX; decrease the production of IgM
rheumatoid factor and leucocyte chemotaxis.
• PK: Rapidly absorbed, 99% protein bound; metabolized in
liver, excreted in urine and bile, plasma t1/2 is 2 days
• ADR: similar to ibuprofen
• Use: long-term anti-inflammatory agent used for rheumatoid
and osteo-arthritis. Also used for acute bout, musculoskeletal
injuries in dentistry.
• Dose: 10, 20 mg cap.

12. Acetic acid derivatives (Ketorolac)
• Potent analgesic but moderate anti-inflammatory agent
• Efficacy is similar to morphine; inhibits PG synthesis
• PK: 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 noninfective ocular conditions.
• Dose: 10 mg tab, 30 mg inj, 0.5% eye drops

13. Acetic acid derivatives (Indomethacin)
• Potent anti-inflammatory drug with prompt
antipyretic action.
• Highly potent inhibitor of PG synthesis and suppress
neutrophil.
• PK: 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

14. Preferential COX-2 inhibitors (Diclofenac)
• An analgesic-antipyretic-anti- inflammatory drug
• Inhibits PG and some what COX-2 selective
• PK: 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 NSIDs. Rheumatoid, and
osteo-arthritis, ankylosing spondylitis, renal colic, posttraumatic and post-operative inflammatory condition.
• Dose: 50 mg entrecoted tab, 100 mg SR, 1% topical
ointment, 1% eye drops.

15. Selective COX-2 inhibitors (Celecoxib)
• 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.
• PK: 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. Paraaminophenol derivative
(paracetamol)
• Central analgesics, Paracetamol has negligible antiinflammatory 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.
• Use: OTC, analgesics. Choice of drug for osteo-arthritis,
best drug to be used antipyretic.
• ADR: Safe and well tolerated. Nausea and rashes occur
occasionally. Leukopenia is rare.

17. Paraaminophenol derivative
(paracetamol)
• Acute paracetamol poisoning: Occur in small children
who have low hepatic glucuronide conjugating ability.
Early manifestations are just nausea, vomiting,
abdominal pain and liver tenderness with no impairment
of consciousness. After 12-18 hr centrilobular hepatic
necrosis and hypoglycaemia that may progress coma.
• Paracetamol is not recommended in premature infants (<
2kg) for fear of hepatotoxicity.
• Treatment: gastric lavage. Active charcoal is given orally
to prevent further absorption. N-acetylcysteine 150
mg/kg should be infused 1.v. over 15 min, followed by
same dose i.v. over the next 20 hr./ 75 mg/kg given orally
every 4-6 hr for 2-3 days.

18. Antirheumatoid and Antigout Drug
• These are drugs which (except corticosteroids), can
suppress the rheumatoid process and bring about a
remission, but do not have nonspecific antiinflammatory or analgesic action.
• Rheumatoid arthritis (RA) is an autoimmune disease
in which there is joint inflammation, synovial
proliferation and destruction of articular cartilage.

19. Antirheumatoid Drug
Disease modifying antirheumatic drugs (DMARDs)
Nonbiological drugs
• Immunosuppressants:
Methotrexate, Azathioprine, Cyclosporine
• Sulfasalazine
• Chloroquine or Hydroxychloroquine
• Leflunomide
Biologic response modifiers (BRMs)
• TNF α inhibitors: Etanercept, Infliximab, Adalimumab
• IL-1 antagonist: Anakinra
Adjuvant drugs
Corticosteroids: Prednisolone and others

20. Antigout Drug
Gout It is a metabolic disorder characterized by hyperuricaemia
[Uric acid, a product of purine metabolism] (normal plasma urate
1-4 mg/dl).
• For acute gout
NSAIDs
Colchicine
Corticosteroids
• For chronic gout/ hyperuricaemia
• Uricosurics: Probenecid, Sulfinpyrazone
• Synthesis inhibitor: Allopurinol, Febuxostat

21. Antigout Drug
• MOA
NSAIDs: (Indomethacin, naproxen, sulindac)
Colchicine: MOA is not clear, prevents
polymerization of tubulin into
microtubules and inhibit leukocyte migration and phagocytosis. Its also inhibit cell
mitosis.
Corticosteroids
• Probenecid: Is an organic acid, reduces urate levels by acting at the anionic
transport site in the renal tube to prevent reabsorption.
• Allopurinol:
Used to treat chronic, tophaceous gout. Inhibit the synthesis of
uric acid by xanthine oxidase, an enzyme that convert hypoxanthine to xanthine
and xanthine to uric acid.

22. Thank you