The Pharmacology of Pain

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Author:
mfawcett
ID:
179115
Filename:
The Pharmacology of Pain
Updated:
2012-10-22 17:37:07
Tags:
pain drugs opiates
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Description:
excitation, sensitisation, , modulation, drugs
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  1. Primary hyperalgesia caused by
    Pro-inflammatory mediators: PGE2 and bradykinin
  2. Secondary hyperalgesia caused by
    changes in the strength of connections to 2nd order neurons in the dorsal horn of the SC
  3. Internal factors exciting nociceptors (4)
    ATP, bradykinin, high [K+], acid
  4. Sensitizing agents (5)
    NO, NGF, prostaglandins, serotonin, histamine
  5. Both sensitise and excite nociceptors
    bradykinin, ATP, H+
  6. Ion channel: heat
    TRPV1
  7. Ion channel: extreme heat
    TRPV2
  8. Ion channel: acid
    ASID (acid sensitive ion channel)
  9. Ion channel: extreme cold
    TRPA1
  10. Ion channel: mechanical stimuli
    TRPV4
  11. Ion channel: ATP
    P2X
  12. Na channels in nociceptive nerve terminals
    Nav1.7 and 1.8
  13. Sensitisation mechanism of PGE2
    • Gs -> AC -> cAMP -> PKA -P-> Nav1.8 (lowers threshold of activation
    • or cAMP -> activates Ih (inward Na current)
  14. Sensitisation mechanism of bradykinin
    -> Gq -> PLC -> PIP2 -> DAG -> PKC -P-> TRPV1 (at 2 sites, lowers heat threshold at which channels are activated)
  15. NSAIDs: method, 3 egs
    • Inhibit COX 1 and 2 -> inhibit prostaglandin release
    • eg aspirin, ibuprofen, diclofenac
  16. Opiates: method, egs (2)
    • Decrease cAMP via u opioid receptor
    • eg morphine, fenatyl
  17. Icatabant
    bradykinin B2 receptor antagonist (not used)
  18. dexamethasone
    • steroidal anti-inflammatory drug
    • downregulates transcription of genes for proteins like COX 2 and bradykinin B1 and B2 receptors (involed in inflammation)
  19. diclofenac
    NSAID: inhibits COX1+2 and therefore prostaglandin release
  20. fenatyl
    opioid: decreases cAMP via u opioid receptor
  21. celecoxib
    COX-2 specidic inhibitor: fewer GI side effects, but had cardic side effects -> mostly withdrawn
  22. ketamine
    NMDA receptor antagonist (effects on memory and cognitive functions)
  23. ziconotide
    blocks N type Ca channels (similar to opiates but without addictive side effects)
  24. 3 types of opioid receptor
    mu, sigma, kappa
  25. amitriptyline
    tricyclic antidepressent, seems to be effective against neuropathic pain
  26. imipramine
    tricyclic antidepressent, seems to be effective against neuropathic pain
  27. gabapentin
    antiepileptic drug, off-target effect of inhibiting N-type Ca channels
  28. pregabalin
    antiepileptic drug, off-target effect of inhibiting N-type Ca channels

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