Analgesic drugs

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Analgesic drugs

  1. 1. Analgesic Drugs
  2. 2. Non narcotic NSAIDS •Para – aminophenol derivatives: Paracetamol •Active metabolite of phenacetin
  3. 3. • MOA: weak prostaglandin inhibitor, no anti inflam • TOXIC METABOLITE: N- acetyl – para – iminobenzoquinone • SE: hepatic necrosis
  4. 4. NARCOTIC • Source: Papaver somniferum Papaver bracteatum
  5. 5. Opioids • substances with morphine-like activity • Includes opioid peptides (enkephalins, endorphins, dynorphins) • Acts on the mu (μ), kappa (κ), delta (δ) receptors in the CNS
  6. 6. Biochemistry of Opioid Receptors • linked through G-proteins via inhibition of adenylate cyclase. • facilitate opening of potassium channels • inhibit opening of calcium channels (inhibiting transmitter release)
  7. 7. ACTIONS OF RECEPTORS • MU • Supraspinal analgesia • Respiratory depression • Euphoria/sedation • Physical dependence • Decrease GI motility • Pupil constriction
  8. 8. ACTIONS OF RECEPTORS • KAPPA • Spinal analgesia • Sedation/dysphoria • Pupil constriction
  9. 9. ACTIONS OF RECEPTORS • SIGMA • Dysphoria • Hallucinations • Psychotomimetic effects • Pupil dilation
  10. 10. ACTIONS OF RECEPTORS Delta •analgesia
  11. 11. Selectivity of opioid drugs and peptides for receptor subtypes   μ δ κ Endogenous peptides β-Endorphin +++ +++ +++ Leu-enkephalin + +++ - Met-enkephalin ++ +++ - Dynorphin ++ + +++
  12. 12. Opioids • Full agonist • Maximal effect • morphine, meperidine, methadone, fentanyl, heroine • Partial agonist • Less effect • Codeine, propoxyphene, hydrocodone, oxycodone, buprenorphine
  13. 13. Opioids • Mixed agonist/antagonists • Agonist at certain receptors antagonist at others • Pentazocine, nalbuphine, butorphanol • Antagonist Naloxone, naltrexone
  14. 14. Full agonists 1. Morphine • Prototype/classic opiate • juice of opium poppy seed (Papaver somniferum
  15. 15. “HECk of a DREAM” • “HECk” histamine release- urticaria/ pruritus, brochoconstriction Emesis cardiovascular- hypotension
  16. 16. “HECk of a DREAM” • DREAM depression of cough reflex/ antitussive, dec. GI motility/antidiarrhea, depression of CNS/ sedative respiratory depression euphoria analgesia miosis
  17. 17. Morphine Uses • First line drug for severe pain • Pain associated with MI • Pulmonary edema • *Dextromethorphan- morphine derivative; antitussive
  18. 18. Clinical Pharmacology of Direct Agonists • Morphine • Highly potent opioid for severe pain • Variable duration of analgesia • Long acting oral formulations/rapid IM/IV
  19. 19. ADVERSE EFFECT • Sedation • Constipation • N/V • Urinary retention • Potential for addiction • Respiratory depression
  20. 20. Full Agonists • Meperidine/Pethidine • Anticholinergic pupil dilation rather than miosis • + MAO inhibitors resp depression, fever, seizures • Loperamide- meperidine analog for diarrhea
  21. 21. Clinical Pharmacology of Direct Agonists • Meperidine • Shorter duration of action than morphine • Cause decrease in spasm and preferred for pancreatitis • Lowers seizure threshold • Absolute contraindication for patients taking MAOI to prevent serotonin syndrome
  22. 22. Full Agonists • Methadone • Controlled withdrawal of addicts; oral • Fentanyl • 80x more potent than morphine • + droperidol dissociative anesthesia • IV, transdermal
  23. 23. Full Agonists • Heroine • Diacetylmorphine • Lipophilic, crosses BBB more quickly • Hydrolyzed to morphine
  24. 24. Partial Agonists • Codeine • Antitussive • For moderate pain
  25. 25. Clinical Pharmacology of Direct Agonists Codeine Less potent than morphine Used for moderate pain, antitussive and for diarrhea Additive analgesia when combined with acetaminophen or aspirin
  26. 26. Clinical Pharmacology of Direct Agonists • Oxycodone • Similar to codeine • Typically combined with acetaminophen • Hydrocodone • Similar to codeine • Typically combined with acetaminophen
  27. 27. Mixed Agonist/Antagonist • Nalbuphine • Analgesia during labor
  28. 28. Clinical Pharmacology of Mixed Agonist-antagonists• Pentazocine (Darvon) • less potency and efficacy than morphine for pain relief • Less addictive and less respiratory depression than morphine • May cause cardiovascular stimulation at high doses • Nalbuphine • Similar to pentazocine • Morphine-like potency • Butorphanol • Similar to pentazocine • Morphine-like potency
  29. 29. Clinical Pharmacology of Partial Agonist- Antagonists • Buprenorphine • Partial agonist than morphine due to receptor dissociation • used as an alternative to methadone for heroin detoxification ANTAGONIST • Naloxone(Narcan) • Partial antagonist used to treat opioid overdose • Short half-life so repeated doses required • Naltrexone • Similar to naloxone • Longer acting
  30. 30. NATURAL • Morphine • Codeine • Thebaine – precursor substrate for the synthesis of naloxone
  31. 31. SEMI - SYNTHETIC • Heroin – diacetylmorphine, diamorphine • Apomorphine –emetic • Hydrocodone – antitussive • Oxycodone • Hydromorphone –analgesic • Oxymorphone
  32. 32. PURELY SYNTHETIC • Methadone • Loperamide,diphenoxylate • Meperidine • Fentanyl • Tramadol • pentazocine

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