Opioid introduction and receptors 2

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Opioid introduction and receptors 2
2014-04-04 22:39:36
Opioid introduction receptors
Opioid introduction and receptors
Opioid introduction and receptors
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  1. What is the biochemical cause of withdrawal symptoms?
    Very high cAMP concentrations
  2. What are the symptoms of withdrawal?
    • Tremor
    • Irritability
    • Alternating chills and sweating
    • Increased heart rate and blood pressure
    • Anorexia
    • Weight loss
    • Abdominal cramping
    • Muscle spasms
    • Crying
  3. Opioids will exhibit one of three structure-dependent activities, what are they?
    • Pure agonist
    • Agonist/Antagonist
    • Pure antagonist
  4. What receptor do pure opioid agonists act on?
  5. (True/False) Pure agonists can be full or partial.
  6. (True/False) Pure opioid agonists produce potent analgesia plus all typical morphine side effects.
  7. (True/False) Agonist/antagonist analgetics produce potent plus all typical morphine side effects.
    • False:
    • Agonist/antagonist analgetics produce potent analgesia BUT their side effect profile differs from pure mu agonists
  8. All clinically utilized agonist/antagonists are _____ agonists and ______ antagonists.
    All clinically utilized agonist/antagonists are K agonists and mu antagonists
  9. Do agonist/antagonists cause euphoria, why or why not?
    No, they antagonize the mu receptor
  10. Do agonist/antagonists cause addiction, why or why not?
    No, they antagonize the mu receptor or cause euphoria
  11. What is the use limiting side effects of agonist/antagonists and what receptor mediated them?
    • K receptor
    • Dysphoria and cardiovascular toxicity
  12. Clinically useful analgesia produced from agonist/antagonists, is mediated by what receptor?
  13. (True/False) Mu agonism is produced by most agonist/antagonists?
    True, though it is small compared to K agonism and mu antagonist
  14. Pure antagonist will produce potent analgesia without morphine side effects.
    • False:
    • No analgesia or morphine side effects at any dose
  15. All clinically utilized pure antagonists will antagonize what receptor types?
    • All opioid receptor types
    • Have their highest affinity for the mu receptor
  16. Opioid receptors are highly stereoselective for what conformation?
    Levorotatory (-) isomers
  17. Opioid receptors are not as highly stereoselective for Dextrorotatory (+) isomers, but they still bind well.
    False, do not bind well to these receptors
  18. Both (+) and (-) isomers of many mu agonists are potent __________.
  19. What is a common example of a dextrorotary (+) mu agonist?
    Dextromethorphan (Robitussin DM)
  20. Does Dextromethorphan have good opioid binding ability?
  21. What is levomethorphan?
    Potent, full mu receptor agonist related to dextromethorphan
  22. What are the CNS effects of opioids?
    • Analgesia without loss of consciousness
    • Euphoria
    • Dysphoria
    • Drowsiness
    • N/V
    • Miosis
    • Respiratory depression
    • Suppression of cough reflex
  23. Tolerance to opioids develops rapidly or slowly?
  24. Euphoria and addiction occurs more in the absence of what?
  25. Tolerance to Drowsiness and dulled thinking capabilities usually occurs within what time frame after starting therapy?
    1-2 days
  26. How do opioids cause Nausea and vomiting?
    Direct stimulation of chemoreceptor trigger zone
  27. Why do opioids cause Miosis?
    By excitatory action on the autonomic segment of the nucleus of the oculomotor nerve
  28. How long does it take to develop tolerance to Miosis effects of opioids?
    Tolerance does not develop to this SE
  29. Respiratory depression occurs through what mechanism of opioid action?
    • Direct effect on the brainstem respiratory centers
    • Which leads to a decrease in responsiveness to CO2 levels in the blood
  30. Due to the respiratory effects of opioids, they must be avoided in patient with what concomitant diseases?
    Emphysema and Cor pulmonale
  31. Opioid induced respiratory depression is most common in what group of patients?
  32. What ailment seems to antagonize Opioid induced respiratory depression?
  33. Tolerance to the respiratory depression effects of opioids occurs in what time frame?
    Relatively quickly (1-2 days)
  34. What is the non-stereoselective actions of the mu opioids?
    Suppression of cough reflex
  35. What are the Cardiovascular effects of mu agonists?
    Peripheral arteriolar and venous dilatation
  36. What are the GI Tract effects of mu agonists?
    • Decreased gastric motility and secretions, leading to constipation
    • Can be severe and use-limiting.
  37. Tolerance to the GI Tract effects of opioids occurs in what time frame?
    There is no tolerance to opioid-induced constipation
  38. What are the Skin effects of mu agonists?
    • Dilation of cutaneous blood vessels (possibly due in part to histamine release)
    • Pruritus with the mu agonist codeine and some analogs (caused by the release of histamine)
  39. What are the Endocrine effects of mu agonists?
    Decreased testosterone levels in males
  40. The mu receptor is coupled to what?
    Both a Gi and a Go
  41. What do interactions of mu opioids at the Go coupled receptor cause?
    • Augments the analgetic response:
    • K+ efflux by opening ATP-gated channels
    • Cause Intracellular Ca+2 levels to decrease
    • Leads to a desensitized, lower firing neuron
  42. The Kappa receptor is coupled to what?
    Both Gi and Go proteins
  43. (True/False) The effect of Kappa Gi receptors is the same as for mu receptors.
  44. (True/False) The effect of Kappa aognists on Go receptors is the same as for mu agonist receptors.
    • False same outcome (neuronal firing), but different route of action
    • Kappa: directly decrease Ca influx into cells
    • Mu: works through ATP-gated channels and K efflux
  45. (True/False) Kappa agonists are potent analgetics.
  46. In general Kappa or Mu agonist produce more portent analgesia?
  47. What subpopulation is more responsive to Kappa agonists?
  48. Do women respond well to mu agonists?
  49. Kappa receptors are found in what peripheral tissue, which mediates what SE?
    • The heart
    • Enhanced cardiac workload (with some)
  50. Do Kappa agonists induce more or less respiratory depression and constipation than mu agonists?
  51. What are the use-limiting SE of Kappa agonists?
    • Sedation
    • Diuresis
    • Dysphoria
  52. Why do Kappa agonists have a decreased risk of addiction?
    Do not induce euphoria
  53. Kappa-induced dysphoria involves inhibition of the same systems that prodce euphoria in mu agonists.
  54. How do Kappa agonist cause dysphoria?
    • Direct inhibitory effect on presynaptic dopaminergic neurons
    • Resulting in decreased in dopamine release
  55. What is the Delta receptor coupled to?
    Both Gi and Go proteins
  56. Delta receptors preferentially bind what type of ligand?
    Peptides (Enkephalins)
  57. (True/False) Delta receptors preferentially bind alkaloids, like opioid drugs.
  58. (True/False) Delta receptors may be involved in the respiratory depression effect of alkaloidal opioids.
  59. The active site of mu and Kappa receptors is found in what portion of the G-protein coupled receptor?
    • Transmembrane and extracellular domains
    • Key sites include: transmembrane domains 3, 6 and 7
  60. The majority of our clinically useful opioid analgetics and antagonists bind to which receptor?
  61. What residue anchors the agonist AND antagonist at the mu opioid receptor?
  62. What type of interaction anchors the agonist OR antagonist to the ASP residue?
  63. (True/False) the anionic site anchors the agonist OR antagonist to the mu receptor.
  64. The kappa receptor has an anchoring _____ residue, which will bind to cationic kappa ligands through an _______ bond.
    • ASP
    • ion-ion
  65. Mu agonists bind to an “agonist site” that contains what type of residues?
    Hydrophobic and aromatic
  66. Hydrophobic and aromatic residues of the Mu “agonist site” will bind to what part of the agonist and through what type of interactions?
    Lipophilic and Nitrogen substituents through hydrophobic and Van der Waals
  67. The “antagonist site” of the mu receptor is a narrow channel, how large is it?
    Admits a three carbon chain
  68. What characteristics does at least one of the residues in the “antagonist site” of the mu receptor have?