Opioid Analgesics & AntagonistsNur Hesti Kusumasari, dr

Opioid AnalgesicsClassification : Spectrum of Clinical Uses :AnalgesicsAntitussiveAntidiarrheal drugsStrength of Analgesia :Strong analgesiaModerate analgesiaWeak AnalgesiaRatio of Agonists to Antagonist Effects :Agonists (receptor activator)full or partialAntagonists (receptor blocker)Mixed agonist-antagonists (capable of activating one opioid receptor subtype & blocking another subtype)

PharmacokineticsMost drugs are well absorbed orally & can be given parenterallyOpioid drugs are widely distributed to body tissuesThey cross the placental barrier & exert effects on the fetusThe opioid are metabolized by hepatic enzymes

Mechanism of action Interaction with specific opioid receptors in the CNS & peripheral tissuesThree major opioid receptors are , , & receptor : contributed to analgesia, respiratory depression, physical dependence receptor : contributed to spinal analgesia & sedative effects of opioid drugsOpioid receptors are thought to be activated by endogenous peptides under physiologic conditions.these peptides are enkephalins, dynorphin, beta-endorphinIonic mechanisms

The EffectsAcute Effects Analgesia :Strong agonists (morphine, methadone, meperidone, fentanyl, levorphanol, heroin)Mild to moderate agonists (codeine, hydrocodone, oxycodone)Weak agonists (propoxyphene)Sedation & euphoria :These effects occur at doses below maximum analgesia dosesAt higher doses, the drugs may cause mental clouding, stuporous, or comatose stateRespiratory depression :Decreased response to carbondioxide challengeAntitussive actions :Suppression of the cough

The EffectsNausea & vomitusCaused by activation of the chemoreceptor trigger zone & are increased by ambulationGastrointestinal effects :Constipation (decreased intestinal peristalsis, which is probably mediated by effects on opioid receptors in the en teric nervous systemSmooth muscle :Contraction of biliary tract muscleIncreased uretral & bladder sphincter toneReduction in uterine tone Miosis :Pupillary coonstriction, is a characteristics effects of all opioid except meperidine

The EffectsChronic EffectsToleranceInvolve receptor uncouplingPhysical dependenceIs an anticipated physiologic responese to chronic therapy with drugs in this group, particularly the strong agonistsAbstinence syndrome (rinorrhea, lacrimation, chills, gooseflesh, muscle aches, diarrhea, yawning, anxiety, & hostility

Clinical UsesAnalgesia To treatment of moderate to severe painCough suppressionInclude codein & dextromethorphan (orally)Treatment of diarrheaInclude diphenoxylate & loperamide (selective antidiarrheal opioids)Management of acute pulmonary edemaMorphine (parenterally) is useful in acute pulmonary edema because its hemodynamics action & its calming effects to relief of the pulmonary symptomsAnesthesiaAre used as preoperative medications & intraoperaive adjuntive agentsOpioid dependenceMethadone is used in the management of opioid withdrawal states & in maintenance programs for addicts

ToxicityOverdoseComa with marked respiratory deppression & hypotensionTreatment : naloxone, ventilatory supportDrug interactionsInteraction with ethanol, sedative hypnotic, anesthetic, antipsychotics drugs, tricyclic antidepressants, & antihistamine (additive CNS deppression)

Mixed agonist-antagonists & Partial Agonist drugsMixed agonist-antagonists drugs :Prototype : butorphanol, nalbuphine, pentazocineAre agonists with weak antagonists activityPartial Agonists drugs :Prototype : buprenorphineIs a partial agonists at receptor

Mixed agonist-antagonists & Partial Agonist drugsEffects :Sedation at analgesic dosesDizzines, sweating, nausea, anxiety, hallucinations, nightmaresLess intense respiratory deppression than with pure agonistsLess toleranceLess physical dependence

Opioid AntagonistsPrototype : naloxone (duration of action 1-2h), naltrexone (24-48h)Clinical uses : management of acute opioid overdoseGiven intravenously