16205534
| Question | Answer |
| Types of Pain (3) | Nociceptors stimulated by inflammation, chemicals + trauma Neuropathic actual nerve damage - burning/heavy sensation + numbness Dysfunctional absence of peripheral origin, chronic, diffuse hyperalgesic pain |
| Nociceptive pain pathway | noxious stimuli -> CNS can be inhibited by spinal pathways from CNS (PAG = endogenous opioids) |
| Inflammatory mediators in nociceptive pathway (6) | Substance P + cGRP excite nociceptors + elicit pain, causes vasodilation + spreads oedema Globulin + Protein kinases Histamine released by mast cells -> excites nociceptors Nerve growth factor binds to TrkA receptors -> excites nociceptors Serotonin, ACh, ATP, H+ excite nociceptors Arachidonic acid metabolised to PGs = block K+ efflux released from nociceptors = additional depolarisation = more sensitive nociceptors |
| Endogenous opioids (+precursor) + opioid receptors | Endorphins (from pro-opiomelanocortin) = miu Enkephalins (from pro-enkephalin) = delta Dynorphins (from pro-dynorphin) = kappa |
| Opioid receptor | 7 transmembrane G-protein-like receptor found in pre+post-synpatic neurons in CNS and periphery activate GPCR = inhib cAMP = hyperpolarisation (open K+, close Ca2+) sedation less GI transit respiratory depression |
| MoA of miu-opioid receptors | found in dorsal horn of spinal cord activated by descending + local circuit inhibitory neurons presynaptic terminal = miu-opioid receptor activation = less Ca2+ influx in response to incoming AP postsynaptic neuron = miu-opioid receptor activation = more K+ conductance = less postsynaptic response to excitatory neurotransmission |
| Non-classical opioid receptors/lingands | Nociceptin receptor (family ORL 1) = similar structure to opioid receptor but doesn't bind opiates w/ high affinity Nociceptor ligand = similar to dysnorphin pharmacological effects not reversed by opioid antagonists |
| Pain treatments (4) | NSAIDs = decrease sensitisation Opioids = - presynaptic NT release + hyperpolarise postsynaptic Anticonvulsants = - excitation by blocking Na+ channels + opening K+ Tricyclic antidepressants = + action of inhibitory NTs |
| Opiates | Compounds related to alkaloids found in poppy seeds (eg. morphine) |
| Opioids | Natural/synthetic compounds that cause opiate-like effects |
| Opioid receptor subtypes | miu = most analgesic effects + major SEs delta + kappa = activate some analgesia kappa = mainly elicit sedation, dysphoria + hallucinations |
| Morphine | miu, dleta + kappa receptor agonist + pain threshold w/out LoC (miu + kappa) euphoria (miu) dysphoria (kappa) |
| Pharmacokinetics of Morphine | variable 1st pass metabolism t1/2 = 3-4hrs |
| SEs of Morphine (8) | Sedation Resp depression nausea/vomiting constipation miosis immunosuppression histamine release = vasodilation, itching, bronchoconstriction contract biliary sphincter muscle |
| Limitations of Morphine (2) | Tolerance Dependance - psychological + physical |
| Opioid Agonist Subtypes (3) | Weak agonists Strong agonists Opioid partial agonists |
| Weak agonists (2) | Codeine Tramadol |
| Codeine | low efficacy - miu>kappa 10% converted to morphine antitussive + diarrhoea |
| Tramadol | weak miu agonist synthetic codeine analogue = inhib NA + serotonin uptake SE - resp depression, + risk of seizure, serotonin syndrome, physical dependance |
| Strong agonists (2) | Fentanyl Methadone |
| Fentanyl | 100x more potent than morphine Highly lipid soluble rapid onset of resp depression sufentanil = 1000x more potent than morphine |
| Methadone | similar to morphine but longer duration of action (t1/2 > 24hrs) treatment of opioid addiction |
| Opioid partial agonist | Buprenorphine |
| Buprenorphine | mixed agonist-antagonist receptor modulator can display full antagonism w/ full agonist - euphoria, - sedation, milder withdrawal + affinity to receptors than other opioids treatment of opioid addiction (w/ naloxone) mild pain relief in non-opioid tolerant people |
| Opioid antagonists | Naloxone |
| Naloxone | miu>kappa antagonist alone = inert given w/ morphine = reverse opioid actions (eg. resp depression in acute opioid OD) short t1/2 = 1-2hrs = need repeat administration |
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