This document summarizes key information about opioid analgesics including: 1. It classifies opioids based on their strength from strong to weak and lists examples in each category. 2. It outlines several clinical uses of opioids such as for analgesia, cough suppression, and treatment of opioid dependence. 3. It describes the pharmacokinetics of opioids including absorption, metabolism, and ability to cross the placental barrier and affect fetuses. 4. It explains the mechanism of action of opioids including their binding to μ, δ, and κ receptors in the brain and spinal cord to produce effects like analgesia and respiratory depression.

1. Opioid Analgesics

2. Strong Morphine Methadone Meperidine Moderate Codeine Oxycodone Weak Propoxyphene Mixed (agonists- antagonists) Buprenorphine, nalbuphine

3. Antagonists Naloxone Naltrexone

4. Clinical Uses Analgesia- Fentanyl, morphine Cough Supression- Codeine, Dextromethorphan. Antidiarrheal- Diphenoxylate, Loperamide Acute Pulmonary edema- Morphine Anesthesia- Fentanyl Opioid Dependence- Methadone

5. Pharmacokinetis Well absorbed orally Morphine, hydromorphone, oxymorpine undergo first-pass metabolism. Cross placental barrier and effect fetus, cause respiratory depression, physical dependence in neonates. Metabolism: by hepatic enzymes, inactivated by glucuronide conjugates before elimination from kidneys. Morphine -6- glucuronide (analgesic) Morphine-3- glucuronide ( neuroexcitatory)

6. Mechanism of action Opioids produce analgesia by binding to specific G protein coupled receptors in brain & spinal cord

7. Mechanism of action Receptors μ , δ , κ receptors. All 3 subtypes are involved in antinociceptive and analgesic mechanisms at both spinal and supraspinal levels. μ receptors -respiratory depressant+ GI δ receptors- development of tolerance κ receptors- involved in sedation + GI

9. Opioid peptides β -endorphin, ( μ ,receptors) Enkephalins ( δ receptors ) Dynorphins ( κ receptors) Modulate transmission in brain, spinal cord, adrenal medulla and neural plexus of gut.

10. All 3 receptors are in high concentration in dorsal horn of spinal cord. Direct application of opioid agonists at spinal cord produce regional analgesia. Resp. depression, nausea, vomiting, sedation from supraspinal action.

11. Ionic Mechanisms Presynaptic level close voltage gated Ca+ channels, and reduce transmission. Post synpatic level open K+ channels (inhibit post synaptic neurons).

13. EFFECTS Analgesia Most powerful analgesics, Morphine, methadone, meperidine, fentanyl, heroin Sedation and euphoria Respiratory depression Action at medulla lead to respiratory depression . Antitussive effects Suppression of the cough reflex Nausea & vomiting Activation of chemoreceptor trigger zone

14. Side Effects GI effects Constipation with decreased intestinal peristalsis. Smoot muscle Cause contraction of billiary billiary tract SM, inc. ureter and bladder tone, red. Uterine tone (prolong labor) Miosis Tolerence Dependence

15. Toxicity

16. Treatment of Opioid Poisioning