NSAIDs- (for Allied health sciences)


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NSAIDs- (for Allied health sciences)

  1. 1. Pharmacology for Allied health sciences Nonsteroidal Anti-inflammatory Drugs and Antipyretic-Analgesics Dr. S. Parasuraman Faculty of Pharmacy, AIMST UNV
  2. 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. 3. NSAIDs Nonselective COX inhibitors • • • • • • 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 22. Thank you