Analgesic Ladder and Opioids

Study Notes

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

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

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

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

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