Opioids Flashcards
How is pain formed?
1) stimulation of nociceptors
2) release of substance P and glutamate
3) stimulation of afferent nerves
4) decussation of fibres
5) action potential ascends
6) synapse in thalamus
7) project to primary sensory cortex
What are the pain modulators?
Peripherally:
Substantia gelatinosa
Centrally:
Peri aqueductal grey
What are examples of endogenous opioids?
Enkephalins
Dynorphins
B-endorphins
What receptors do opioids act on?
μ - enkephalins, B-endorphins
δ - enkephalins
κ - dynorphins
All GPCRs
What is the WHO analgesic ladder?
Simple analgesia - paracetamol, NSAIDs
Weak opioid - codeine
Strong opioid - morphine, fentanyl
Typically used for chronic pain
If acute pain, can go straight to strong opiate
What is the general principles of opioid use?
Exploit natural opioid receptors - agonist or antagonism
Mainly act via μ receptors
Aim to modulate pain
Also indicated in cough, diarrhoea and palliation
Describe pharmacokinetics of morphine
Absorption:
PO, IV, IM, SC, PR
Erratic gut absorption
Significant first pass
Distribution:
Rapidly enters all tissues, inc foetal
Metabolism:
Morphine + glucuronic acid => M6G + M3G
Elimination:
Renal
What are the actions of morphine?
Strong agonist
Bind to μ receptors
Causes analgesia and euphoria
What are some side effects of morphine?
Respiratory depression - medullary resp centre made less responsive to CO2
Emesis - stimulates CTZ
Decreased GI motility => constipation
Miosis
Mast cell degranulation => histamine release - be careful w/ asthmatics
Describe pharmacokinetics of fentanyl
Absorption:
IV, epidural, intrathecal, nasal
80-100% bioavailability
Distribution:
Highly lipophilic and protein bound
High level of CNS membrane
Metabolism:
CYP 3A4
Elimination:
Half life 6 mins
Renally excreted
What are the actions of fentanyl?
Strong agonist
Analgesia
Anaesthetic
What are the side effects of fentanyl?
Respiratory depression
Constipation
Vomiting
Describe the pharmacokinetics of codeine
Administration:
PO, SC
Metabolism:
Codeine => morphine via CYP 2D6
Elimination:
Glucoronidation of morphine
Renal excretion
What are the actions of codeine?
Moderate antagonist
Mild - moderate analgesia
Cough depressant
What are the side effects of codeine?
Constipation
Respiratory distress
Describe the pharmacokinetics of buprenorphine
Administration:
Transdermal, buccal, sublingual
Distribution:
V lipophilic
Metabolism:
Hepatic via CYP 3A4
Elimination:
Biliary excretion
Therefore safe in renal impairment
Half life 37 hrs
What are the actions of buprenorphine?
Mixed agonist-antagonist
V high affinity for μ receptor, low Kd
Used for moderate to severe pain
Also used for addiction treatment
What are some side effects of buprenorphine?
Respiratory depression
Low BP
Nausea
Dizziness
Describe the pharmacokinetics of naloxone
Absorption:
IV, IM, intranasal, PO
V low bioavailability - extensive first pass metabolism
Rapid onset of action
Distribution:
V lipophilic
Metabolism:
Hepatic => naloxone-3-glucoronide
Elimination:
Renal
What are the actions of naloxone?
Antagonist
Greater affinity than morphine and fentanyl
Competitive antagonism of opioid
What are the side effects of naloxone?
Short half life
Tf give slow infusion - pt has time to metabolise morphine
How does opioid tolerance occur?
When giving synthetic opioids, the number of opioid receptors increases
Requires a higher dose of opioid required to get enough binding for a cell response
How does opioid withdrawal occur?
Suddenly taking away a synthetic opioid means that there is a lower percentage of binding to receptors
Therefore don’t get a cell response
What are the actions of methadone?
Used to avoid withdrawal Sx
Binds to opioid receptors
Slowly decrease dose to decrease number of receptors
Removes some side effects
What are some special considerations for opioids?
Manual labourers/drivers Elderly Bedbound Asthmatics Biliary tract obstruction Respiratory disease Renal impairment Pregnancy
What are some contraindications for opioids?
Hepatic Failure Acute respiratory distress Comatose Head injuries Raised ICP
How are opioids prescribed in palliative care?
Buprenorphine, diamorphine, fentanyl, morphine and oxycodone all prescribed
Tend to ignore special considerations eg renal impairment
Indications: pain, shortness of breath
Also need to manage side effects like nausea and constipation
Why are some opioids controlled drugs?
To prevent:
Misuse
Illegal obtainment
Any harm being caused
