1. The most important and predictable route of administration of opioids perioperatively is the intravenous route, since the amount of drug entering the systemic circulation is precisely known.
2. Opioids given orally have bioavailabilities of 20% to 40% caused by a rapid first-pass effect as a result of opioid metabolism in the liver.
3. Opioids given via the epidural (patient-controlled epidural analgesia) and intrathecal routes need to diffuse into the surrounding nerve tissue and spinal cord to activate MORs.
   1. More lipophilic opioids (fentanyl, sufentanil) will penetrate faster and achieve higher concentrations into the spinal cord than hydrophilic opioids such as morphine and meperidine, yet they are also cleared from the spinal fluid more rapidly.
   2. Thus, the lipophilic opioids may cause an early-onset respiratory depression, whereas morphine tends to cause late ventilatory depression due to its slow clearance from the spinal fluid.
4. Intramuscular injections of opioids for treatment of postoperative pain should be avoided because there are superior alternatives such as the intravenous (IV) administration of opioids using patient-controlled analgesia (PCA) devices.

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