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Basics Opioid Slides

Barry Basics Opiod Slides

QuestionAnswer
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.
TYPES OF OPIOIDS Naturally occurringSemi syntheticSynthetic
NATURALLY OCCURRING OPIOIDS Morphine and Papaverine: Derived from opium, an extract of the poppy plant.
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.
SYNTHETIC OPIOIDS Demerol, Methadone, Fentanyl, Butorphanol, Pentazocine: Manufactured by synthesis rather than chemical modification of morphine.
CLASSIFICATIONS OF OPIOIDS AgonistsAgonist-antagonistsAntagonists (Competitive and Non-competitive)
AGONISTS Capable of eliciting full agonist (morphine-like) effects
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.
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.
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.
WHAT DO OPIOIDS MIMIC? The actions of endogenous ligands (endorphins, enkephalins and dynorphins) by binding to the opioid receptor which activates pain modulating systems.
HOW DO OPIOIDS CAUSE SUPRASPINAL ANALGESIA? By activating postsynaptic opioid receptors in the midbrain and medulla (results in inhibition of pain pathways.
HOW DO OPIOIDS CAUSE SPINAL ANALGESIA? By activating presynaptic opioid receptors (results in decreased release of neurotransmitters involved with nociception).
HOW DO OPIOIDS CAUSE PERIPHERAL ANALGESIA? By activating opioid receptors on primary afferent neurons (antinociceptive activity).
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.
MU-1 RECEPTORS Primarily supraspinal analgesiaSome spinal analgesiaEuphoriaMiosisUrinary retention
MU-2 RECEPTORS Primarily spinal analgesiaRespiratory depressionBradycardiaPhysical dependenceConstipation N/VItching
KAPPA RECEPTORS Spinal and supraspinal analgesiaSedationDysphoria (psychosis)
DELTA RECEPTORS Mostly spinal analgesiaSome supraspinal analgesiaSome respiratory depressionPhysical dependence
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.
HOW IS BILIARY SMOOTH MUSCLE SPASM TREATED? Nitro, Atropine,Naloxone,Glucagon,and Benadryl (?)
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
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!
WHAT ARE THE ACTIVE METABOLITES OF MORPHINE? Morphine 3-glucuronideMorphine 6-glucuronideMorphine 6-glucuronide is a more potent and longer acting agonist than morphine!
HOW IS MORPHINE METABOLIZED? It undergoes biotransformation in the liver.Excreted by the kidneys (problem for pts. who have renal dx.)
HYDROMORPHONE Pharmacokinetic profile similar to morphine.8-10X more potent than morphine.Similar SE profile (less n/v, itching, and dysphoria).No active metabolite.
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.
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.
WHAT IS THE METABOLITE OF MEPERIDINE? Normeperidine: Excreted by the kidneys. Is neurotoxic at high concentrations causing myoclonus and seizures.
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.
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.
WHICH OPIOID CAUSES CHEST WALL RIGIDITY? Fentanyl
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
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.
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.
HOW IS REMIFENTANYL METABOLIZED? By non-specific plasma and tissue esterases.
WHAT ARE THE OPIOID ANTAGONISTS? Naloxone and Naltrexone
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.
HOW LONG DOES NARCAN LAST? Peaks in 1-2 min and lasts 30-45 min.May require redosing.
HOW IS NARCAN MIXED? Mix 1 amp (0.4mg) in 9cc of NS. Give one cc at at a time (20 mcg).
WHAT HAPPENS WITH ABRUPT REVERSAL OF OPIOIDS? Execessive sympathetic stimulation!Arrythmias, Inc HR, Inc BP, N/V, and Pulmonary edema.
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.
WHAT ARE THE OPIOID AGONISTS-ANTAGONISTS (PARTIAL-AGONISTS)? Butorphanol (Stadol)Nalbuphine (Nubain)
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.
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
WHICH PARTIAL AGONIST CAUSES WITHDRAWL IN ADDICTS? Nubain (nalbuphine)
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.
Created by: Christine.scott1 on 2010-04-07



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