PSYCH 265 1st Edition Lecture 19Outline of Last Lecture I. Dependence on ethanol II. Withdrawal from ethanol a. Minor b. Major III. FASDIV. FASV. Characteristics of FASVI. Behavioral characteristics of FASVII. Brain anomalies in FASVIII. Pharmacokinetics of morphine IX. Opioids receptor X. Analgesic effect XI. Hyperalgesic effectXII. Behavioral effects of morphine`Outline of Current Lecture I. Behavioral effects of morphine II. Pupillary effects III. Other central effectsIV. Endocrine effectsV. Gastrointestinal effectsVI. Cardinal signs of morphine overdoseVII. Antidotal therapy VIII. Evzio IX. Naloxone nasal spray X. Tolerance These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.XI. Withdrawal XII. Endogenous opioid peptidesXIII. Endogenous opioid system XIV. Multiple receptors XV. Advantages of delta opioid agonistsXVI. Classes of opioids analgesic drugsXVII. Codeine XVIII. Synthetic opioid drugsXIX. Semisynthetic opioid drugsCurrent Lecture-Behavioral effects of morphine oSedation oEuphoria Stimulation of dopamine in reward centerInitial doses lead to euphoria but at higher doses unpleasant symptoms as delirium hallucination, dizziness and confusion oRespiratory depression Decreased sensitivity of respiratory center in Medulla Oblongata to CO2 -Pupillary effects of morphineoAcute opioid effectPinpoint pupilsoOpioid withdrawal Mydriasis -Other central effects of morphine oAntitussive effect Increased threshold in cough center of medulla oblongata Antitussive dextromethorphan, non-analgesic analog oEmetic/antiemetic effectInitial stimulation of medullary chemoreceptor trigger zone (CTZ)Delayed suppression of inhibition of medullary emetic center-Endocrine effects of morphine oIncreased vasopressin (antidiuretic hormone) release-->oliguria oSuppression of pituitary-gonad axis Decreased gonadotropin release Hypogonadism Men Gynecomastia, decreased testicle size Women Missed menstrual periods, infertility Increased prolactin release -Gastrointestinal effects of morphine oMorphine increases spontaneous digestive smooth muscle contraction---> decreases coordinated peristalsis oOpioids contraindicated in biliary colic -Cardinal signs of morphine overdoseoMiosis (pin-point pupils)oRespiratory depression-->respiratory failureoComa -Antidotal therapy for morphine OD-Naloxone (Narcan) -Supportive respiration -Evzio (Naloxone)oFirst and only naloxone product specifically intended for emergency administration by family members or caregivers in settings where opioids may be present -Naloxone Nasal Spray ob/c many heroin abusers carry hepatitis or HIV virus, the risk of infection to medical personnel is high oSome emergency responders use atomizers to convert the injectable form of naloxone tonasal spray oA nasal spray version of naloxone will prove to be effective, safer and easier to administer than the current injection-based approach -Tolerance to morphine -Tolerance develops to all effects except miosis and constipation -Cross tolerance to other narcotic analgesic drugs -Withdrawal from morphine oNatural withdrawal (cessation of drug taking)Yawning, rhinorrhea, lacrimation, sweating, mydriasis, goose flash at 12-36 hrRetching, vomiting, diarrhea, anorexia, aches and pains, hyperactivity at 48-72 hrHypotension, bradycardia, tachypnea, hypothermia, anorexia, miosis for 25-30 weeks (protracted withdrawal)oPrecipitated withdrawal (administration of antagonistMax withdrawal within minOTHER OPIOIDS RECEPTORS & PEPTIDES-Endogenous opioid peptides oEnkephalins Methionine-enkephalin Leucine-enkephalin oEndorphins Beta-endorphin oEndomorphins oDynorphins -Endogenous opioid system oEndogenous opioid peptides are widely distributed in the brain oEndogenous opioid peptides are involved in a broad range of physiological functions, notjust pain -Multiple opiate receptors oMu opioids receptors Receptor for morphine and most narcotics Endogenous ligand are beta-endorphin and endomorphins oKappa opioid receptors Receptor for mixed agonist/antagoinst Endogenous ligand are dynorphins oDelta opioid receptors Receptor for enkephalins Endogenous ligand are enkephalins -Advantages of delta opioid agonistsoAnalgesic properties generally equal to morphineoMay be more effective than morphine in relief of neuropathic pain oLess addiction liability oLess respiratory depression oLess gastrointestinal side effectOTHER OPIOIDS DRUGS-Classes of Opioids Analgesic DrugsoOpium alkaloids-Morphine -Codeine oSemisynthetic opiates-Hydromorphone -Oxymorphone -Oxycodone -Heroin oSynthetic opiates-Methadone-Meperidine -Fentanyl -Codeine oOpium alkaloid oProdrug that’s converted to morphine oLess potent than morphine b/c only 10% convertedoLower dependence liability than morphine oUsed as antitussive drugoCombined w/ acetaminophen or aspirin for moderate pain -Synthetic opioid drugsoSynthetic manipulations can convert-Morphine-->hydromorphone, oxymorphone -Codeine--->hydrocodone, oxycodone oThese drugs popular of treatment for chronic pain oSome drugs previously listed in schedule II but w/ increase in prescription drug abuse now listed Schedule III -Semisynthetic opioid drugsoSome significant diversion & abuse problems -Oxycontin (oxycodone)-Regular oxycodone 5-15mg-Oxycontin up to 160 mg w/ timed release-Oxycontin reformulated to be harder to crush and dissolve-Zohydro (hydrocodone)-Regular hydrocodone 5-10 mg-Zohydro (hydrocodone) up to 50mg-No abuse deterrent