opioids n.
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  2. OPIOIDS 0 • First, morphine in 1803 with active component opium • Narcotic is greek for stupor and is referred to morphine-like analgesics with potential to produce physical dependence.

  3. OPIODS 0 Opioids act at stereospecific opioid receptors at presynaptic and postsynaptic sites in the central nervous system– brain(periaqueductal gray, amygdala, corpus striam, and hypothalmus) and spinal cord(substanstantia geltinosa) and in the peripheral tissues. Endogenous ligands for the opioid receptors are collectively known as endorphins. The term endorphine comes from endo, meaning inside, and m-orphine, indicating opioid agonist.

  4. OPIOIDS 0 • The endorphines are peptides that are released upon a painful stimuli • They bind to opioid receptors to decrease the individuals perception of pain • Endorphines include enkephlins, endorphines and dynorphins • The opioid agonist mimic the endogenous endorphines and bind to the opioid receptors hence inhibiting pain transmission

  5. OPIOIDS 0 • Ionized state is necessary for strong bonding at the anionic receptor site • Only the levorotatory forms of the opioid exhibit agonist activity • The affinity of most opioid agonists for receptors correlates well with their analgesic potency

  6. OPIOIDS • Opioids receptor activation decreases neurotransmission • Mostly decreasing presynaptic release of acetylcholiene,dopamine,norepinephrine ,substance P(postsynaptic can occur) • Substance P is an excitatory neurotransmitter presumed to be released by terminals of pain fibrs that synapse in the substansia gelatinosa of the spinal cord

  7. OPIOIDS • Opioid receptors are classified as mu, delta, kappa • An ideal opioid agonist would have have high specificity for receptors, producing desirable responses (analgesia) and little or no specificity for receptors associated with side effects ( hypoventilation, nausea, physical dependence)


  9. OPIOIDS • EFFECTS • Cv – not a negative inotrope • Respiratory- decrease respiratory rate and increase tidal volume. • Decrease the co2 response in the medulla • Chest wall rigidity-rapid administration of opioids increases airway pressure • Spasm of biliary smooth muscle-sphincter of Oddi • GI-constipation, N/V(stimulation of the chemotrigger zone floor of fouth ventricle) • Placenta-opioid cross and produce fetal respiratory depression • Miosis-excitatory action of edingerwestphal nucleus of the occularmottor nerve • Awareness-not a hypnotic • Decreases MAC requirements for inhalational anesthetics • Tolerance –occurs 2-3 weeks, dependence 25 days

  10. Onset 15-30min,1/2 time 1.7-3.3 hr 75-85% metab to morphine-3-glucuronide inactive 5-10% metab to morphine 6-glucuronide, produces analgesia and resp depression via mu activation Metab conjugationwtih glucuronic acid Releases histamine MORPHINE OPIOIDS

  11. OPIOIDS • MEPERIDINE • 1/10 as potent as morphine • Duration 2-4 hours • Mu and kappa receptor agonist • Structurally similar to atropine, derived from phenylepiperidine • 90% metabolized to normeperidine,1/2 as active as a analgesic • Normeperidine toxicity causes myoclonus and seizures • No miosis, causes mydriasis, large doses causes decrease in myocardial contractility • Do not administer if patient is taking moa inhibitors,cns excitation hypotension • Treatment for postop shivering


  13. OPIOIDS • FENTANYL-phenylpiperidine derivative • 75-125 more potent than morphine • Rapid onset, highly lipid soluble • First pass-75% initial dose to lungs • Duration of action is by redistribution rather than elimination, slowly released and elimination by the liver-N-demethylation and excreted by the urine

  14. OPIOIDS • FENTANYL • Elimination half time is longer than morphine because Vd is larger and is more lipid soluble • Stable hemodynamic—no cardiac depressant effects, absence of histamine release, suppression of stress response during surgery

  15. 12 times more potent than fentanyl 60% first pass pulmonary uptake Smaller Vd than fentanyl Metabolized N dealkylation ,O demethylation SUFENTANIL OPIOIDS

  16. OPIOIDS • ALFENTA—to fentanyl but 1/5-1/10 as potent with 1/3 duration • Rapid onset 1.4 mins—low PK • 90% nonionized, Vd 4-6 times smaller than fentanyl, lower lipid solubility • Bound to alph1 acid glycoprotein • Metabolized – piperidine N-dealkylation to noralfentanil and amide N-dealkylation to N-phenylpropionamide • Interindividual variability –inhibit metabolism especially alteration in P-450 for those taking erythromycin

  17. OPIOIDS • AGONIST/ANTAGONIST • NALBUPHINE-NUBAIN • Chemically related to oxymorphine and naloxone-as potent as morphine and ¼ as an antagonist • Metabolized in liver with half time of 3 to 6 hours • 10-20 mg IV • Reverses postop ventilatory depression effects of fentanyl maintaining the analgesia

  18. Opioid induced respiratory depression Metabolized conjugation-glucuronic acid to form naloxone 3-glucuronide Half time 60-90 minutes 1-4uq/kg IV Side effects: tachycardia,hypertention,pulmonary edema,cardiac dysrhythmias,vfib Crosses placenta NALOXONE OPIOIDS

  19. Opioids

  20. OPIOIDS • NEURAXIAL • Epidural or subarachnoid placement of opioids are based on mu receptors in the substancia gelatinosa of the spinal cord • Epidural placement of opioids reflect diffusion of the drug across the dura to gain access to the mu opioid receptors on the spinal cord as well as systemic absorption to produce effects similar to those that would follow IV administration

  21. OPIOIDS • Side effects • Pruritus • N/V • Urinary retention • Depression of ventilation • Sedation • Central nervous system excitation • Neonatal morbidity • Viral reactivation • Ocular dysfunction • Sexual dysfunction • GI dysfunction • Thermoregulatory dysfunction • Water retention

  22. OPIOIDS • Factors that increase risk of respiratory depression • High opioid dose • Low lipid solubility • Concomitant administration of parental opiods or other sedatives • Lack of opioid tolerance • Advance age

  23. KETOROLAC • NSAIDs possess analgesic, antiinflamatory, antipyretic,and platelet inhibitory effects • NSAIDs inhibition of cyclooxygenase activity and the resulting decrease in peripheral synthesis of prostaglandins

  24. KETOROLAC • NSAID potent analgesic, moderate antiinflammatory • 30mg IM,produces analgesia that is equivalent to 10 mg of morphine • Has no ventilatory depression or biliary spasm • Metabolized by glucuronic acid conjugation • Clearance is decreased in elderly and dosed less in younger patients

  25. KETOROLAC • SIDE EFFECTS • Bleeding • Life –threatening bronchospasm may follow if administered to patients with Nasal polyposis, asthma, and aspirin sensitivity