14 - Opioids Flashcards
What is the difference between pain and nociception?
Nociceptive pain is pain due to actuall tissue damage (google)
How do we feel pain in general terms?
How can we modulate pain peripherally?
- Centrally: via periaqueductal grey
- Peripherally: via subsantia gelatinosa
How can we modulate pain centrally?
Endogenous opioids like enkephalins released from the periaqueductal grey and inhibit the second order neurone
What are the different types of endogenous opioid receptors and what are their actions when stimulated?
All are GPCRs and all decrease cAMP levels
What is the WHO analgesic ladder?
- Go up the ladder for severe or worsening pain e.g start on morphine straight away for malignany or acute severe pain
- Move down the ladder with resolution of pain
What are opiates used for?
- Mainly act on u-receptors to modulate pain
- Can also be indicated in cough, diarrhoea and palliation
What are the different types of opioids?
- Can range from agonists to anatagonists
- Know the ones in bold plus tramadol, diamorphine and methadone
What is the mechanism of action of morphine?
Strong u-agonist causing analgesia and euphoria
- Absorbed really quickly IV but gut absorption is erratic and low oral bioavailability (40%)
- Distributed across all tissues as lipophillic, including fetus, but cannot get across BBB
- Eliminated renally so be careful with AKI and CKD
What are some of the side effects of morphine?
- Respiratory depression: medullary resp centre less responsive to CO2
- Emesis: as stimilates chemoreceptor trigger zone
- Constipation: due to decrease motility and increased sphincter tone
- Syncope: decreased b.p
- Miosis
- Histamine release causing itch, be careful in asthmatics
- Cannot use in pregnancy
What is the mechanism of action of fentanyl?
Strong u receptor agonist (higher potenticy and affinity than morphine) causing analgesia and anaesthetic
- Given IV, epidural, intrathecal or nasal in children. High bioavailability of 80-100%
- Highly lipophillic and protein bound and can get into CNS
- Metabolised hepatically by CYP3A4
- Renally excreted but less so than morphine so better in AKI and CKD
Why may fentanyl be used instead of morphine?
- Less histamine release, sedation and constipation so less side effects than morphine
- Has a higher affinity for the u-receptor so shifts morphine off
What are the side effects of fentanyl?
- Respiratory depression
- Constipation
- Vomiting
What is the mechanism of action of codeine?
Moderate u-receptor agonist used for mild/moderate analgesia and cough depressant
- Given PO or SC
- Converted to morphine by CYP2D6
- Elimination by glucoronidation of morphine and renal excretion
- 1/10th potency of morphine
What can affect the CYP2D6 enzyme and therefore affect how a patient reacts to codeine?
- Can be inhibited by Fluoxetine and other SSRIs so need lower dose of morphine with this
- Variable expression amongst people