Anesthesia Pharmacology-I AP-I-5 Opiods John P. McDonough, CRNA, Ed.D., ARNP Professor & Director Anesthesiology Nursing

Opium n Derived from the Greek word of juice n Opiate = drug derived from opium –morphine (1803), codeine (1832), papaverine (1848) n Opioid = exogenous substances, natural or synthetic, that bind with certain receptors and produce some morphine like effects

Synthetic Opioids n Contain the phenathrene nucleus of morphine n Important pharmacokinetic & pharmacodynamic differences between drugs

Agonism n Stereospecific opioids receptors n Presynaptic & postsynaptic sites in the CNS –brainstem & spinal cord n Outside CNS –peripheral tissues

Peripheral Receptors n Primary afferent neurons n Endogenous peptide opioid receptor ligands –enkephalins, endorphins, dynorphins n Opioids activate antinoceptive systems n Only levorotatory forms show agonist activity

Opioids n morphine n meperidine n sufentanil n fentanyl n alfentanil n remifentanil n codeine n dextromethoraphan n hydromorphone n oxymorphone n methadone n heroin

Opioid Agonists-antagonists n pentazocine n butorphanol n nalbuphine n buprenophine n nalorphine n bremazocine n dezocine

Opioid Antagonists n naloxone n naltrexone n nalmefene

Mu 1 μ n Effect –analgesia (supraspinal & spinal), bradycardia, hypothermia, urinary retention, low abuse potential n Agonists –endorphins, morphine, synthetic opioids n Antagonists –naloxone, naltrexone, nalmefene

Mu 2 μ n Effect –analgesia (spinal), ventilatory depression, constipation (marked), physical dependence n Agonists –endorphins, morphine, synthetic opioids n Antagonists –naloxone, naltrexone, nalmefene

Kappa κ n Effect –analgesia (supraspinal & spinal), dysphoria, sedation, diuresis, miosis, low abuse potential n Agonists –dynorphins n Antagonists –naloxone, naltrexone, nalmefene

Delta δ n Effect –analgesia (supraspinal & spinal), ventilatory depression, physical dependence, constipation (minimal), urinary retention n Agonists –enkephalins n Antagonists –naloxone, naltrexone, nalmefene

Sigma σ n Effect –dysphoria, hallucinations, ventilatory stimulation n Agonists –pentazocine, nalorphine n Antagonists –naloxone, naltrexone, nalmefene

Morphine

Meperidine

Fentanyl

Sufentanil

Alfentanil