Strong: Morphine, Methadone, Meperidine, Moderate, Codeine, Oxycodone
Weak: propoxyphene, Mixed (Agonists-antagonists), Buprenorphine, Nalbuphine
Antagonists: Naloxone, Naltrexone
Analgesia- Fentanyl, morphine
Cough Suppression- Codeine, Dextromethorphan
Antidiarrheal- Diphenoxylate, Loperamide
Acute pulmonary edema- Morphine
Opioid Dependence- Methadone
- 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-.
Mechanism of Action: Opioids produce analgesia by binding to specific G protein coupled receptors in brain & spinal cord.
Mechanism Of Action:
- Receptors: µ, Ȣ, K receptors
All 3 subtypes are involved in antinociception and analgesic mechanisms at both spinal and supraspinal levels.
- µ receptors- respiratory depressant+ GI
- Ȣ receptors- development of tolerance
- Kreceptors- involved in sedation+ GI
- β- endorphin, (µ, receptors)
- Enkephalins (Ȣ receptors)
- Dynorphins (K receptors)
- Modulate transmission in brain, spinal cord, adrenal medulla and neural plexus of gut.
- All 3 receptors are in high concentration in dorsal horn of spinal cord.
- Direct application of opioid agonists at spinal cord produce regional analgesia.
- Respiratory depression, nausea, vomiting, sedation from supraspinal action.
- Presynaptic level close voltage gated Ca+ channels, and reduce transmission.
- Post synaptic level open K+ channels (inhibit post synaptic neurons)
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
- GI effects
Constipation with decreased intestinal peristalsis
- Smooth muscles
cause contraction of biliary track SM, ureter and bladder tone, ted, Uterine tone (prolong labor)