9 - 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
What are the side effects of codeine?
- Severe constipation so prescribe laxatives with them
- Respiratory depression especially in children so don’t give to under 12s
What is the mechanism of action of buprenorphine?
Mixed agonist/antagonist of u receptor for moderate to severe pain or opioid addiction treatment
- Absorbed transdermally (patch for 72 hours) or buccal/sublingual
- Very lipophillic so can get into CNS
- Metabolised by CYP3A4 and glucoronidation
- Eliminated mainly biliar>renal so good in renal impairment but long half life of 37 hours
How does buprenorphine compare to morphine?
- Higher affinity for u receptors but lower efficacy
- Long duration of action
- Not easily displaced
- Can be antagonist at k receptors
Can be used in renal impairmenta but morphine cannot and can also stop the drowsiness that comes with morphine
What are the side effects of buprenorphine?
- Respiratory depression
- Nausea
- Low b.p and dizziness
Side effects not as bad as other opiates as only partial agonist
What is the mechanism of action of naloxone?
Antagonist of U receptor used for competitive antagonism of opioid
- Given IV or IM as very low oral bioavailability but rapid action as liophillic
- Metabolised hepatically but renally excreted after 30-60 minutes
- Given slow infusion
What are the side effects of naloxone and why is it given via slow infusion for opiate OD?
- Short half life so slow infusion needed
- If fast infusion it would bring the patient around too quickly and they would still have high levels of opiate in the body, slow allows the opiate to be excreted before the patient comes around
How do people develop an opioid tolerance?
- Phosphorylation and uncoupling: decreased sensitivity of u receptor and G protein becomes uncoupled from receptor due to presence of arrestin so decreased cAMP
- cAMP production: when you remove the opioid there is a rebound effect and an increased level of cAMP so increased depolarisation, increased neuronal excitability and withdrawal symptoms like sweating, vomiting etc
Why do you get systemic withdrawal effects with opioid withdrawal?
- U-receptors all over the body
- Rebound effect
- 1 in 4 people getting prescribed opiates will get an addiciton
What is the cause of death with an opiate overdose and how do we reverse this?
- Usually respiratory depression: increased CO2 but resp rate doesn’t increase so get acidotic and die
- Can give naloxone (not bolus) to reverse
- Can decrease effects with delta and 5HT4 agonists
When should you be careful with prescribing opiates?
When should you never prescribe morphine/other opiates?
Giving an opiate could mask symptoms of a head injury, e.g may think drowsiness is due to the morphine
What opiates are used for palliative care and when are they indicated?
- Buprenorphine, diamorphine, fentanyl, morphine
- Tend to ignore the special considerations
- Given when there is pain and SOB
- Make sure you manage side effects like nausea and constipation with laxatives and anti-emetics
- Explain to relatives it is normal for it to slow resp rate down and it isn’t speeding up dying process just making more comfortable
What are some controlled drugs and how are they controlled?
- When written out have to write your name, the date and the address
- Write the patients name and addrwss
- Write the form of drugs and the units
- Total volume in words and figures
What is the mechanism of action of tramadol?
Acts at serotonin and u receptors and is used for moderate to severe pain
How does methadone help with opioid tolerance?
- Enough stimulation of opioids receptor to stop withdrawals
- Higher affinity than other opioids so not much difference if patient takes an opioid on top of methadone so discourages them from using it
