NSAIDs- (for Allied health sciences)
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NSAIDs- (for Allied health sciences) NSAIDs- (for Allied health sciences) Presentation Transcript

  • Pharmacology for Allied health sciences Nonsteroidal Anti-inflammatory Drugs and Antipyretic-Analgesics Dr. S. Parasuraman Faculty of Pharmacy, AIMST UNV
  • 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).
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 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
  • 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
  • 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. 10 hr. • Dose: 100 and 200 mg cap.
  • 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.
  • 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.
  • 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.
  • 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
  • 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
  • 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.
  • Thank you