NSAIDs- (for Allied health sciences)Presentation Transcript
Pharmacology for Allied health sciences
Drugs and Antipyretic-Analgesics
Dr. S. Parasuraman
Faculty of Pharmacy, AIMST UNV
• 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).
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.
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.
• 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
• NSAIDs are don’t reverse the process of rheumatic
diseases rather, they slow destruction of cartilages
and bone and allow patients increased mobility.
• Aspirin is acetylsalicylic acid. It is rapidly converted in the
body to salicylic acid which is responsible for its
• Aspirin is a weaker analgesic than morphine (600 mg ~codeine
• The analgesic action is mainly due to prevention of PGmediated sensitization of nerve endings of peripheral nervous
• Aspirin resets the hypothalamic thermostat and rapidly
reduces fever by promoting heat loss (sweating, cutaneous
vasodilatation), but does not decrease heat production.
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.
• 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
• Decrease glomerular filtration rate (in renal insufficiency
• Prolog bleeding time
• Salicylates are not recommended during pregnancy they
may cause postpartum hemorrhage.
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.
– 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.
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.
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
• ADR: nausea, abdominal pain, loose stools, pain in
• 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
Acetic acid derivatives (Indomethacin)
• Potent anti-inflammatory drug with prompt
• Highly potent inhibitor of PG synthesis and suppress
• 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
• Use: arthropathies, psoriatic arthritis and acute gout
• Dose: 25 mg cap, 75 mg cap, 1% eye drop
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.
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.
• Dose: 100 and 200 mg cap.
• Central analgesics, Paracetamol has negligible antiinflammatory action.
• Poor inhibitor of PG synthesis and more active on COX in
• 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.
• 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.
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.
Gout It is a metabolic disorder characterized by hyperuricaemia
[Uric acid, a product of purine metabolism] (normal plasma urate
• For acute gout
• For chronic gout/ hyperuricaemia
• Uricosurics: Probenecid, Sulfinpyrazone
• Synthesis inhibitor: Allopurinol, Febuxostat
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
• Probenecid: Is an organic acid, reduces urate levels by acting at the anionic
transport site in the renal tube to prevent reabsorption.
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.