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Barry Basics Opiod Slides

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OPIOIDS   Exogenous substances that specifically bind to several sub-populations of opioid receptors and produce agonist (morphine like) effects.Used during induction to decrease sympathetic response to laryngoscopy and during maitenance and post-op for analgesia.  
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TYPES OF OPIOIDS   Naturally occurringSemi syntheticSynthetic  
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NATURALLY OCCURRING OPIOIDS   Morphine and Papaverine: Derived from opium, an extract of the poppy plant.  
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SEMI SYNTHETIC OPIOIDS   Heroin, Hydrmorphone, Thebain (not used by itself - is a precursor for oxycodone and oxymorphone): Result from simple modifications of the morphine molecule.  
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SYNTHETIC OPIOIDS   Demerol, Methadone, Fentanyl, Butorphanol, Pentazocine: Manufactured by synthesis rather than chemical modification of morphine.  
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CLASSIFICATIONS OF OPIOIDS   AgonistsAgonist-antagonistsAntagonists (Competitive and Non-competitive)  
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AGONISTS   Capable of eliciting full agonist (morphine-like) effects  
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AGONIST-ANTAGONISTS   Bind to Mu receptors and produce limited responses (partial agonist) or no effect (competitive antagonist) But.....may also have agonist effects at other receptors.  
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ANTAGONISTS   Competitive: binds to receptor but can be knocked off if a higher concentration of the agonist is present.Non-competitive: Very strong affinity for receptor. NOT DISPLACED by high concentrations of the agonist.  
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MOA   Bind at receptors to block transmission of pain.Receptors in dorsal horn of spinal cord, the brain (supraspinal), and peripheral tissue.Receptors endogenously activated by: endorphins, enkephalins and dynorphins.  
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WHAT DO OPIOIDS MIMIC?   The actions of endogenous ligands (endorphins, enkephalins and dynorphins) by binding to the opioid receptor which activates pain modulating systems.  
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HOW DO OPIOIDS CAUSE SUPRASPINAL ANALGESIA?   By activating postsynaptic opioid receptors in the midbrain and medulla (results in inhibition of pain pathways.  
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HOW DO OPIOIDS CAUSE SPINAL ANALGESIA?   By activating presynaptic opioid receptors (results in decreased release of neurotransmitters involved with nociception).  
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HOW DO OPIOIDS CAUSE PERIPHERAL ANALGESIA?   By activating opioid receptors on primary afferent neurons (antinociceptive activity).  
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OPIOID RECEPTORS   Discovered: Early 1970'sConstantly revised: intitially thought to be Mu, Kappa and Sigma, NOW Mu, Delta and Kappa which have many subtypes.Each receptor has a different function.Desired effects come mostly from action at Mu receptors.  
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MU-1 RECEPTORS   Primarily supraspinal analgesiaSome spinal analgesiaEuphoriaMiosisUrinary retention  
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MU-2 RECEPTORS   Primarily spinal analgesiaRespiratory depressionBradycardiaPhysical dependenceConstipation N/VItching  
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KAPPA RECEPTORS   Spinal and supraspinal analgesiaSedationDysphoria (psychosis)  
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DELTA RECEPTORS   Mostly spinal analgesiaSome supraspinal analgesiaSome respiratory depressionPhysical dependence  
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CHARACTERISTICS COMMON TO ALL OPIOIDS.   Dose-dependent ventilatory depression (decreased RR with compensatory increased TV)Not reliable at producing LOC: some sedation,but main effect is analgesia.May stimulate chemoreceptor trigger zone.Cause spasm of biliary smooth muscle.  
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HOW IS BILIARY SMOOTH MUSCLE SPASM TREATED?   Nitro, Atropine,Naloxone,Glucagon,and Benadryl (?)  
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MORPHINE   The Prototype: E 1/2 time is 1.5-3hrs.Doseages: Intra-op- 0.1-1 mg/kg IV Post-op- .05-0.2mg/kg IV .03-0.15 mg/kg IV  
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WHAT IS THE MAJOR FEATURE OF MORPHINE?   Histamine release!Signs and symptoms: local redness, itching and hives. Decreased BP and Increased HR and flushing.Slow administration reduces this risk!  
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WHAT ARE THE ACTIVE METABOLITES OF MORPHINE?   Morphine 3-glucuronideMorphine 6-glucuronideMorphine 6-glucuronide is a more potent and longer acting agonist than morphine!  
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HOW IS MORPHINE METABOLIZED?   It undergoes biotransformation in the liver.Excreted by the kidneys (problem for pts. who have renal dx.)  
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HYDROMORPHONE   Pharmacokinetic profile similar to morphine.8-10X more potent than morphine.Similar SE profile (less n/v, itching, and dysphoria).No active metabolite.  
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MEPERIDINE   1st synthetic opioid.1/10 the potency of morphine.E 1/2 time: 3-5hrsDose: 0.5-1 mg/kg IM and 0.2-0.5 mg/kg IVStructure: Similar to atropine. Increases HR, Mydiasis (eyes dilate) and dry mouth.  
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WHICH OPIOID IS GIVEN IN PACU FOR SHIVERING?   Meperidine: Mechanism is unclear, but it is believed that meperidine stimulates the kappa receptors which decreases the shivering threshold. Is an agonist at alpha-2 receptors.  
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WHAT IS THE METABOLITE OF MEPERIDINE?   Normeperidine: Excreted by the kidneys. Is neurotoxic at high concentrations causing myoclonus and seizures.  
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WHICH OPIOID IS UNSAFE TO GIVE TO PATIENTS ON MAOI'S LIKE NARDIL?   Meperidine:Causes a severe excitatory state: signs and symptoms include: Increase in HR, BP and Temp. Delerium, seizures and possible death.  
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FENTANYL   Structurally related to meperidine.100x more potent than morphine.E 1/2 time: 3-6 hours.Doseages: Intra-op- 2-10 mcg/kg. CT surgery- 30-50 mcg/kg. Post-op-0.5-1.5 mcg/kg.Minimal CV depression: may decrease HR.1cc = 50 mcg.  
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WHICH OPIOID CAUSES CHEST WALL RIGIDITY?   Fentanyl  
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SUFENTANYL   7-10x more potent than fentanyl.Intra-op dose: 0.2-0.8 mcg/kgCT surgery: 10-30 mcg/kgE 1/2 time: 2.5-3.5 hours  
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ALFENTANYL   1/5-1/10 As potent as fentanyl.Intra-op dose: 10-100 mcg/kgE 1/2 time: 1.5 hrs.More rapid onset and shorter duration of action then fentanyl and sufentanyl.  
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REMIFENTANYL   Similar potency as fentanyl.Extremely rapid onset, clearance and recovery.E 1/2 time: 15-30 min.Dose: 1 mcg/kg IV over 60-90sec then 0.25-1mcg/kg or 0.05mcg/kg/min.  
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HOW IS REMIFENTANYL METABOLIZED?   By non-specific plasma and tissue esterases.  
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WHAT ARE THE OPIOID ANTAGONISTS?   Naloxone and Naltrexone  
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NALOXONE   Also known as Narcan.Most frequently used.Great affinity for Mu receptors and is a competitive antagonist.Used to reverse unconciousness from narcotic overdose.Reverses respiratory depression: give in 20-40mcg increments.  
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HOW LONG DOES NARCAN LAST?   Peaks in 1-2 min and lasts 30-45 min.May require redosing.  
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HOW IS NARCAN MIXED?   Mix 1 amp (0.4mg) in 9cc of NS. Give one cc at at a time (20 mcg).  
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WHAT HAPPENS WITH ABRUPT REVERSAL OF OPIOIDS?   Execessive sympathetic stimulation!Arrythmias, Inc HR, Inc BP, N/V, and Pulmonary edema.  
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NALTREXONE   Also known as Trexan.Longer acting anatagonist given in PO form for addicts.May last up to 24 hoursPatients who take this may have a temporary resistance to narcotics.  
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WHAT ARE THE OPIOID AGONISTS-ANTAGONISTS (PARTIAL-AGONISTS)?   Butorphanol (Stadol)Nalbuphine (Nubain)  
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BUTORPHANOL   Partial AgonistProduces analgesia and respiratory depression similar to 10mg of morphine.More sedation than Nubain.Incidence of dysphoris is low.Does not increase biliary pressure.Can be used to tx post-op shivering.Dose: 0.5-3mg IV.  
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NALBUPHINE   Partial agonist at kappa and Mu recceptors.Like morphine analgesia.Less sedative than Stadol.Will reverse respiratory depression but not analgesia.Used for itching from morphineCan be given IV or IMDose: 5-10mgCan cause withdr  
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WHICH PARTIAL AGONIST CAUSES WITHDRAWL IN ADDICTS?   Nubain (nalbuphine)  
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WHAT IS FLUMAZENIL?   A BENZODIAZEPINE ANTAGONIST!!!!! (competitive)Reversal can be total or partial, depends on dose.High affinity for Benzo receptors but minimal intrinsic activity.Dose: usually 0.2mg increments titrated to effect. Not to exceed 1mg.  
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