1. Most opioid analgesics act at multiple receptor systems with different affinities. (Morphine acts with high affinity at MOR and with lower affinities at KOR and DOR.)
2. Methadone is the most potent NMDA receptor antagonist. Antagonism of the NMDA receptor is clinically useful in reducing opioid tolerance and opioid-induced hyperalgesia (OIH) and in chronic pain states leading to pain hypersensitivity.
3. Nonopioids may also act at opioid receptors.
   1. Ketamine is an NMDA receptor antagonist with affinity for multiple receptor systems, including the opioid receptors.
   2. Its anesthetic properties are related to its effect at the NMDA receptors, and its analgesic effects are predominantly caused by MOR activation.

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