1. A major breakthrough in the understanding of opioid pharmacology came from a series of discoveries of opioid receptors, endogenous opioid peptides, their encoding genes, and endogenous opioid alkaloids.
2. The endogenous opioid system is composed of a family of structurally related endogenous peptides that act at a four-member opioid receptor family consisting of the µ-opioid receptor (MOR), κ-opioid receptor (KOR), δ-opioid receptor (DOR), and orphanin FQ/nociception (NOP) receptor.
   1. At least three MOR subtypes have been described: µ ₁ is predominantly involved in opioid analgesia, µ ₂ is involved in opioid-induced respiratory depression, and µ ₃ is involved in opioid-induced immune suppression.
   2. Functional validation of most opioid receptor subtypes awaits the development of antagonists with sufficient selectivity to allow a clear differentiation by effect.
   3. The endogenous opioid peptides include endorphins, enkephalins, and dynorphins, each of which display different affinities for the µ-, κ-, and δ-opioid receptors. β-endorphins have a high affinity for the µ-opioid receptor, met- and leu-enkephalins for the κ-opioid receptor, and dynorphin A for the δ-opioid receptor.
3. Opioids act not only through central and peripheral neuronal pathways but also via nonneuronal mechanisms, such as actions on the immune system. Opioid receptors are linked to G proteins in the cell membrane and hence are members of the large G-protein–coupled receptor (GPCR) family. GPCRs mediate a cascade of downstream signaling pathways.

Opioids

1. Short History
2. The Endogenous Opioid System
3. Opioid Receptor Knockout Mice
4. Classification of Exogneous Opioids
5. Opioids Acting at Opioid and Nonopioid Receptors
6. Opioid Mechanisms
7. Routes of Administration
8. Pharmcokinetics (PK) and Pharmacodynamics (PD)
9. PKPD Models for Opioid Effect: which End Point Serves the Clinician Best?
10. Pharmacodynamics: Dose Effect on Pain Relief
11. Pharmacogenetics
12. Opioid-Induced Respiratory Depression
13. Other Opioid-Related Side Effects
14. Remifentanil for Obstetric Labor Pain
15. Gender Differences