Analgesic Ladder and Opioids

Analgesic Ladder and Opioids

• Amitriptyline is used to treat persistent moderate pain
• Step 1 of the analgesic ladder involves using NSAIDs or Acetaminophen
• Step 2 involves using less potent opioids like Hydrocodone, Codeine, or Tramadol
• Step 3 involves using potent opioids like Morphine or Oxycodone

Endogenous Opioid Peptides

• The first endogenous opioid peptide is Enkephalin
• Enkephalin is found as a mixture of peptides differing in their terminal amino acids, including Met-enkephalin and Leu-enkephalin
• The transient action of Enkephalin is due to rapid degradation by amino peptidases, particularly the degradation of the Tyr-Gly bond

Opioid Receptors and Effects

• Most clinically used opioid drugs bind to Mu-opioid receptors
• Activation of Mu-opioid receptors produces effects such as analgesia, respiratory depression, euphoria, and decreased gastrointestinal motility

Pain Classification and Treatment

• Inflammatory pain originates from infection or inflammation
• Neuropathic pain is complex and results from nerve system injury
• Analgesic adjuvants include tricyclic antidepressants, anticonvulsants like Gabapentin and Pregabalin, and topical analgesics like lidocaine patches
• Mild pain can be treated with non-opioids or NSAIDs like Acetaminophen, with or without analgesic adjuvants

Opioids and Their Uses

• Morphine is a prototype ligand for Mu-opioid receptors and is obtained from plants
• Codeine is obtained from the methylation of Morphine and has analgesic effects due to its conversion to Morphine via O-demethylation
• Heroin is a synthetic derivative of Morphine with rapid metabolism to Morphine, leading to euphoric effects
• Hydromorphone is more potent than Morphine and is marketed as an analgesic agent
• Hydrocodone is an antitussive agent often combined with Acetaminophen or Aspirin for pain treatment
• Oxycodone is a beta-hydroxyl version of Hydrocodone and is marketed in combination with Acetaminophen/Aspirin/Ibuprofen