Morphine and Opioid Analgesics

Morphine and Opioid Analgesics

1. Definitions, terminology & sources of opioids

• Pain (algesia) is an unpleasant sensory and emotional experience evoked by a noxious stimulus; it is primarily protective but causes suffering and is the commonest symptom bringing a patient to the physician (KDT 8e Ch.34, p.497; Katzung 16e Ch.31, p.582).
• Analgesic = a drug that selectively relieves pain by acting on the CNS or on peripheral pain mechanisms without significantly altering consciousness; analgesics relieve pain as a symptom without affecting its cause (KDT 8e Ch.34, p.497).
• Analgesics are classified into three groups: (A) opioid / narcotic / morphine-like; (B) non-opioid / non-narcotic / aspirin-like (NSAID, antipyretic-antiinflammatory) — covered elsewhere, NOT in this topic; (C) adjuvant analgesics — anticonvulsants (gabapentin, pregabalin, carbamazepine, lamotrigine) and antidepressants (amitriptyline, duloxetine) (KDT 8e Ch.34, p.497).
• Opium — dark-brown resinous material from the unripe capsule of the poppy Papaver somniferum (and P. album); contains two alkaloid classes (KDT 8e Ch.34, p.497; G&G 14e Ch.23, p.443; Katzung 16e Ch.31, p.582):
  • Phenanthrene derivatives: morphine (~10% of opium), codeine (~0.5%), thebaine (~0.2%, non-analgesic — a synthetic precursor).
  • Benzylisoquinoline derivatives: papaverine (~1%, smooth-muscle relaxant, non-analgesic), noscapine (~6%, antitussive, non-analgesic).
• Terminology (precise definitions):
  • Opiate — the naturally occurring opium alkaloids (morphine, codeine, thebaine, papaverine) plus semisynthetic derivatives chemically related to morphine (e.g. oxycodone) that bind the µ receptor (G&G 14e Ch.23, p.443; Katzung 16e Ch.31, p.582).
  • Opioid — the broader term: any agent (natural, semisynthetic, fully synthetic, or endogenous peptide) that binds the orthosteric site of an opioid receptor; thus pethidine and the endorphins are opioids but not opiates (KDT 8e Ch.34, p.497; G&G 14e Ch.23, p.443).
  • Narcotic — originally meant sleep-inducing ("benumbing", Greek narkotikos); in the USA it is now chiefly a legal term (Katzung 16e Ch.31, p.582; G&G 14e Ch.23, p.443).
• Historical: opium known since antiquity (Eber's papyrus 1500 BC); Sertürner isolated and named morphine (after Morpheus, Greek god of dreams) in 1803–1806 (KDT 8e Ch.34, p.497; Katzung 16e Ch.31, p.582; G&G 14e Ch.23, p.443).
• Morphine remains the prototype and the standard against which all strong analgesics are compared (Katzung 16e Ch.31, p.582; KDT 8e Ch.34, p.498).