O slideshow foi denunciado.
Utilizamos seu perfil e dados de atividades no LinkedIn para personalizar e exibir anúncios mais relevantes. Altere suas preferências de anúncios quando desejar.
Próximos SlideShares
What to Upload to SlideShare
Avançar

12

Compartilhar

Non-Steroidal Anti-inflammatory Drugs ( NSAIDs) PART II PROF SATYA 2019

This is an interesting and novel PPT on the Pharmacology of NSAIDs, on drugs other than aspirin ( for Aspirin check NSAIDs PART I ) illustrated with beautiful pictures and flowcharts....!!

Audiolivros relacionados

Gratuito durante 30 dias do Scribd

Ver tudo

Non-Steroidal Anti-inflammatory Drugs ( NSAIDs) PART II PROF SATYA 2019

  1. 1. DR.V.SATHYANARAYANAN M.B.B.S., M.D., ACME PROFESSOR OF PHARMACOLOGY NSAIDs II
  2. 2. PARACETAMOL (ACETAMINOPHEN )  Para-amino Phenol derivative  Analgesic like aspirin and has additive action with aspirin  Good and promptly acting antipyretic  But has negligible anti-inflammatory action  Poor inhibitor of PG synthesis in peripheral tissues but more active on COX in brain  UNLIKE ASPIRIN  does not stimulate respiration or affect acid-base balance or increase cellular metabolism, no CVS action, not uricosuric
  3. 3. PARACETAMOL – PK and ADVERSE EFFECTS  Well absorbed orally, uniformly distributed  Metabolism by  glucuronide and sulfate conjugation  Rapidly excreted in urine  T1/2  2-3 hrs, effects last for 3-5 hrs  SAFE and WELL TOLERATED  Nausea, rashes  occasional  Gastric irritation is insignificant – mucosal erosion, bleeding occur rarely only in overdose  Does not affect platelet function or clotting factors
  4. 4. PARACETAMOL - USES  Most commonly used ‘OVER-THE COUNTER’ ANALGESIC  Headache, mild migraine, Dysmenorrhoea, musculoskeletal pain etc  Relatively ineffective when inflammation is prominent  First choice analgesic for osteoarthritis  Fever due to any cause, especially in children ( except heat stroke )
  5. 5. ADVANTAGES OF PARACETAMOL OVER ASPIRIN  Safer in terms of gastric irritation, ulceration and bleeding  Can be given to ulcer patients  Used in all age groups ( infants to elderly)  Does not prolong bleeding time  Hypersensitivity reactions are rare  No metabolic effects  No acid-base disturbances  Safe in pregnant/lactating women  Safe in the presence of other diseases  No significant drug interactions
  6. 6. ACUTE PARACETAMOL POISONING  Occurs especially in children ( low hepatic glucuronide conjugating ability )  > 10 g in an adult  serious toxicity  Fatalities common > 250 mg/kg  MANIFESTATIONS  Nausea, vomiting, abdominal pain and liver tenderness, no impairment of consciousness ( EARLY)  AFTER 12-18 HRS  centrilobular hepatic necrosis, May be accompanied by renal tubular necrosis and hypoglycemia  may progress to COMA  JAUNDICE  starts after 2 days  High plasma levels  hepatic failure and death  Lower levels  recovery with supportive treatment
  7. 7. MECHANISM OF TOXICITY  N-acetyl-p-benzoquinoneimine (NABQI) is a highly  reactive arylating metabolite of paracetamol  detoxicated by conjugation with glutathione.  When a very large doses of paracetamol are taken the glucuronidation capacity is saturated more NABQI is formed,  hepatic glutathione is depleted  NABQI binds covalently to proteins in liver cells (and renal tubules) causing necrosis.  In chronic alcoholics even 5 g/d can result in hepatotoxicity  because ethanol induces CYP 2E1, that metabolizes Paracetamol to NABQI.
  8. 8. TREATMENT  Induce vomiting or Gastric lavage  Activated charcoal is given orally or through the tube  to prevent further absorption  Other supportive measures ( A B C )  SPECIFIC ANTIDOTE : N–acetylcysteine 150 mg/kg infused I.V in 200 ml 5% Glucose solution over 15 minutes followed by same dose I.V over next 20 hours  Or 75 mg/kg may be given orally every 4-6 hours for 2-3 days  Started 16 hours or more after paracetamol ingestion  INEFFECTIVE  It replenishes glutathione stores of liver  prevents binding of toxic metabolite to other cellular constituents
  9. 9. NONSTEROIDAL ANTI- INFLAMMATORY DRUGS (NSAIDs)  Common therapeutic indications  Common adverse effects  Different pharmacokinetics and potency  Different chemical families  Common mechanism of action (cyclooxygenase inhibition)  Different selectivities to COX I and II Similarities more striking than Differences..!!
  10. 10. PROPIONIC ACID DERIVATIVES  Ibuprofen  Naproxen  Ketoprofen  Flurbiprofen
  11. 11. IBUPROFEN  SAFEST TRADITIONAL NSAID  Better tolerated alternative to aspirin  more efficacious than aspirin 650 mg +codeine 60 mg in relieving dental surgery pain  Weaker antiinlammatory  Milder side effects  Gastric discomfort, nausea, vomiting  most common  CNS side effects headache, dizziness, tinnitus , blurring vision  Hypersensitivity reactions  rashes, itching infrequent  Ppt aspirin induced asthma  Fluid retention  less marked  C/I  PREGNANCY, PEPTIC ULCER
  12. 12. IBUPROFEN – PK & INTERACTIONS  Well absorbed orally  90-99% bound to plasma proteins  Displacement reactions are not significant  Likely to decrease the efficacy of antihypertensives  Enters brain, synovial fluid  Crosses placenta  Metabolized in liver --. Hydroxylation and glucuronide conjugation  Excreted in urine and bile  Abolishes the antiplatelet and cardio protective effect of low dose aspirin
  13. 13. IBUPROFEN – USES  Available as an “over the counter” drug  Used as a simple analgesic and antipyretic as aspirin  Particularly effective in dysmenorrhoea  Widely used in rheumatoid arthritis, osteoarthritis and other musculoskeletal disorders especially where pain is predominant  Soft tissue injuries, Fractures  Tooth extraction  Postpartum and post operatively  suppress pain & inflammation
  14. 14. NAPROXEN  Similar to Ibuprofen  Stronger anti-inflammatory activity  Potent in inhibiting leukocyte migration  more valuable in acute gout  750 mg stat followed by 250 mg 8 hourly  Also recommended for rheumatoid arthritis and ankylosing spondylitis  Longer t1/2  suppress platelet function  Gastric bleeding more common than ibuprofen  Carries lower thrombotic risk  Reduce the dose in elderly  MORE EFFICACIOUS AND BETTER among propionic acid derivatives
  15. 15. KETOPROFEN  Antiinflammatory efficacy  similar to ibuprofen  Side effects are more  Additional actions  stabilize lysosomes and inhibit LOX
  16. 16. FLURBIPROFEN  Has Additional mechanisms of antiinflammatory actions  MORE EFFECTIVE THAN IBUPROFEN  Gastric side effects are also more  Also used as an OCULAR ANTIINFLAMMATORY
  17. 17. FENAMATE – MEPHENAMIC ACID  ANALGESIC, ANTIPYRETIC AND WEAKER ANTIINFLAMMATORY DRUG  SIDE EFFECTS  Diarrhoea  most important,  Epigastric distress, CNS side effects, Skin rashes  Hemolytic anemia  rare but serious  PK  Slow oral absorption, highly bound to PP  USES  Primarily as an analgesic for muscle , joint and soft tissue pain  250-500 mg TDS  Quite effective in dysmenorrhoea  May be useful in some cases of rheumatoid arthritis and osteoarthritis
  18. 18. PIROXICAM  Enolic acid derivative  Long acting potent antiinflammatory  Good analgesic and antipyretic  Nonselective reversible inhibitor of COX  Inhibit inflammation in diverse ways  inhibit WBC Chemotaxis, decreases free radicals production, IgM Rheumatoid factor  PK  rapidly absorbed, 99% protein bound, enterohepatic cycling occurs,  long t1/2  2 days  single daily dose
  19. 19. PIROXICAM – ADR & USES  GI side effects  more than ibuprofen  Low doses are better tolerated and less ulcerogenic than indomethacin  Ulcer, bleeding  frequent in higher doses  Rashes, pruritus, edema, reversible azotemia  USES Suitable for use as long-term antiinflammatory drug in rheumatoid arthritis, ankylosing spondylitis, osteoarthritis etc  Also used in dentistry, acute gout, musculoskeletal injuries  higher toxicity  NOT A FIRST CHOICE DRUG
  20. 20. TENOXICAM  Congener of piroxicam  Similar properties and uses
  21. 21. ACETIC ACID DERIVATIVES  Ketorolac  Indomethacin  Nabumetone
  22. 22. KETOROLAC  Potent analgesic but modest antiinflammatory  Equalled the efficacy of morphine in postoperative pain  Free of opioid side effects  Inhibits PG synthesis  Rapidly absorbed after oral, I.M administration  Highly plasma protein bound  t1/2  5-7 hours
  23. 23. KETOROLAC – ADR and USES  GI side effects  nausea, dyspepsia, abdominal pain, ulceration, loose stools  CNS side effects  drowsiness, headache, dizziness  SKIN  pruritus  Rise in serum transaminases, fluid retention  USES  POSTOPERATIVE, DENTAL, MUSCULOSKELETAL PAIN  15-30 mg I.M or I.V every 4-6 hours  Also used for renal colic, migraine, metastases in bone  Non infective ocular conditions  Orally  for short term management of moderate pain
  24. 24. KETOROLAC – PRECAUTIONS AND CONTRAINDICATIONS  Continuous use for more than 5 days  NOT RECOMMENDED ( risk of GI and renal toxicity )  Preanaesthetic medication  C/I  Obstetric analgesia  C/I  Not for RH. Arthritis or osteoarthritis
  25. 25. INDOMETHACIN  is a potent nonselective COX inhibitor  may also inhibit phospholipase A and C, reduce neutrophil migration, and decrease T cell and B cell proliferation.  indicated for use in juvenile rheumatoid arthritis, gout and ankylosing spondylitis, postepisiotomy pain, etc.  It has been used to treat patent ductus arteriosus.  An ophthalmic preparation seems to be efficacious for conjunctival inflammation and to reduce pain after traumatic corneal abrasion.  Gingival inflammation is reduced after oral rinse.  A high incidence (up to 50%) of GI and CNS side effects is produced: GI bleeding, diarrhoea, frontal headache, mental confusion, etc.
  26. 26. Acetic acid derivatives sulindac  prodrug– metabolite is 500times more potent  adverse skin reactions aceclofenac  has significant analgesic and anti-inflammatory effect  with good tolerance (low occurrence of GIT adverse effects)  higher adherence to treatment of chronic diseases
  27. 27. DICLOFENAC  is a phenylacetic acid derivative.  A 0.1% ophthalmic preparation is recommended for prevention of postoperative ophthalmic inflammation and can be used after intraocular lens implantation and strabismus surgery.  A topical gel containing 3% diclofenac is effective for solar keratoses.  Diclofenac in rectal suppository form can be considered a drug of choice for analgesia and postoperative nausea.  It is also available for intramuscular and oral administration  – SR tablet: 100 mg/24 h).  Side effects occur in approximately 20%: GI distress and occult bleeding, gastric ulceration.  A preparation combining diclofenac and misoprostol (PGE1) decreases upper GI ulceration but may result in diarrhoea.
  28. 28. Clinical uses DICLOFENAC  A) Any inflammatory conditions  B) Musculoskeletal pain  C) Dysmenorrhoea  D)Acute gouty arthritis  E) Fever  F) Locally to prevent or treat post opthalmic inflammation  G) A topical gel for solar keratoses
  29. 29. COX-2 inhibitors (1) Selective COX-2 inhibitors (Coxibs) • Celecoxib • Etoricoxib • Parecoxib (2) Preferential COX-2 inhibitors • Meloxicam • Nimesulide • Nabumetone
  30. 30. • are selective COX-2 inhibitors • They exert antiinflammatory, analgesic, and antipyretic action with low ulcerogenic potential. • can cause infertility. •They have prothrombotic cardiovascular risk. COXIBS
  31. 31. • is as effective as other NSAIDs in the treatment of rheumatoid arthritis and osteoarthritis • in trials it has caused fewer endoscopic ulcers than most other NSAIDs. • because it is a sulfonamide, celecoxib may cause rashes. • It does not affect platelet aggregation at usual doses. • It interacts occasionally with warfarin – Celecoxib
  32. 32. •is a second-generation COX-2-selectiveinhibitor with the highest selectivity ratio of any coxibs. •has an eliminationt1/2 of 22 h. •for the treatment of the symptoms of osteoarthritis (60 mg once daily) and rheumatoid arthritis (90 mg once daily), •acute gouty arthritis (120 mg once daily), and for the relief of acute musculoskeletal pain (60 mg once daily). •Ninety mg daily of etoricoxib has superior efficacy compared with 500 mg of naproxen twice daily in the treatment of rheumatoid arthritis over 12 weeks. • Etoricoxib has similar efficacy to traditional NSAIDs for osteo arthritis, acute gouty arthritis, and primary dysmenorrhea and has a GI safety profile similar to other coxibs. Etoricoxib
  33. 33. •is an enolcarboxamide •preferentially inhibit COX-2 over COX-1, • particularly at its lowest therapeutic dose of 7.5 mg/d. •It is not as selective as the other coxibs • may be considered “preferentially" selective rather than “highly” selective. •approved for the treatment of osteoarthritis and rheumatoid arthritis. •It is associated with fewer clinical GI symptoms and complications than piroxicam, diclofenac, and naproxen.. Meloxicam
  34. 34. •is a derivative of pyrazolone. •It is a potent and promptly acting analgesic, antipyretic, and spasmolytic but has poor antiinflammatory and not uricosuric activity. •Analgin can be given orally, i.m. as well as i.v. (very slowly). •Pain at the i.m. injection site and rarely abscess can occur. Occasionally an i.v. injection produces fall in BP. • Few cases of agranulocytosis were reported and •metamizole was banned in the USA and some European country. •However, it has been extensively used in Bulgaria and many other as well as in India and Russia. •Adverse reaction data collected over four decades shows that the risk of serious toxicity with metamizole is very low than with Aspirin or many other NSAIDs. METAMIZOLE
  35. 35. Comparative action between COX inhibitors COX-1/COX-2 inhibitors COX-2 inhibitors 1. Analgesic action (+) (+) (+) 2. Antipyretic action (+) (+) 3. Antiinflammatory action (+) (+) (+) 4. Antiplatelet aggregatory (+) (-) 5. Gastric mucosal damage (+) (+) (+) (+) 6. Renal salt / water retention (+) (+) 7. Delay/prolongation of labor 8. Infertility (+) (+) (-) (+) (+) (+) 9. Ductus arteriosus closure (+) ? 10. Aspirin-like asthma 11. Cardiotoxicity (+) (-) ? (+) (+)
  36. 36. Prevention of Adverse effects  Dose reduction  Combination with protective drugs  Antiulcerotics– proton pump inhibitors (lansoprazole, omeprazole)  prostaglandine analogues (substitution)  H2 antihistamines – (cimetidine, ranitidine, famotidine)  antacids  think about selective COX-2 inhibitors
  37. 37. THANK YOU!
  • Narayanamurthy24

    Jul. 9, 2021
  • ankeet24

    Mar. 28, 2021
  • VijaySoni98

    Jan. 8, 2021
  • IsaacMakhanu1

    Dec. 11, 2020
  • AshahNassozi

    Oct. 6, 2019
  • neelu2014

    Aug. 20, 2019
  • KhaterZaman

    Jul. 23, 2019
  • dineshkumar2542

    Jun. 29, 2019
  • GouriubYadav

    May. 18, 2019
  • GouriubYadav

    May. 18, 2019
  • PriyanjliRana1

    Apr. 26, 2019
  • RitikaNarawade1

    Mar. 19, 2019

This is an interesting and novel PPT on the Pharmacology of NSAIDs, on drugs other than aspirin ( for Aspirin check NSAIDs PART I ) illustrated with beautiful pictures and flowcharts....!!

Vistos

Vistos totais

677

No Slideshare

0

De incorporações

0

Número de incorporações

6

Ações

Baixados

0

Compartilhados

0

Comentários

0

Curtir

12

×