16 Opioids Flashcards
Differentiate between nociception and pain.
Nociception= non concious neural traffic due to trauma or potential trauma to tissue
Pain= complex, unpleasant awarness of sensation modified by experience, expectation, immediate context and culture
How do we feel pain? (explain the pathway)
- Nociceptors stimulated
- Release Substance P and Glutamate
- Afferent nerve stimulated
- A delta fibres= sharp pain
- C fibres= dull pain
- Fibres decussate then ascend
- Synapse in thalamus
- Project to post central gyrus
We can modulate pain peripherally and centrally. Where can the modulators be found?
Peripherally: substantia gelatinosa
Centrally: peri aqueductal grey
How do we modulate pain peripherally?
Substantia gelatinosa
How do we modulate pain centrally?
Name 3 endogenous opioids.
Enkephalins
Dynorphins
B-endorphins
What receptors do the endogenous opioids act on? (3) Where are each of these receptor types found and what actions do they have?
Outline the WHO analgesic ladder:
What drug types might be give to treat neuropathic pain?
Anticonvulsants
Tricyclics
Serotonin/Noradrenaline reuptake inhibitors
In general, how to opioids work?
Exploit endogenous opioid receptors
Main effect= via μ- receptors
Aim to modulate pain
(Also indicated in: - cough, diarrhoea, palliation)
There are many different drugs in the opioid class. Give an example of a:
Strong agonist
Moderate agonist
Mixed agonist/antagonist
Antagonist
Strong agonist
- Morphine
- Fentanyl
Moderate agonist
- Codeine
Mixed agonist/antagonist
- Buprenorphine
Antagonist
- Naloxone
How is morphine administered? Why does it sometimes need to be administered IV rather than orally?
Orally
IV
Intramuscular
Sub cut
PR
Gut absorption erratic and only has 40% oral availability due to first pass metabolism
Can morphine enter the foetal tissue?
Yes- can enter all tissues including foetal BUT not very good at crossing blood brain barrier compared to other opioids
Where is morphine metabolised and excreted?
Metabolised: liver
Excreted: renally
What action does morphine have? How does it work?
Strong affinity for μ-receptors, minimal for K and δ.
Complete activation of μ
Actions:
- Analgesia
- Euphoria
Give 6 side effects of morphine:
How is fentanyl abdministered? What’s its bioavailability like?
Fentanyl
Administered:
- IV
- Epidural
- Intrathecal (into CSF)
- Nasal
Bioavailability:
- 80-100%
How well does Fentanyl cross the blood brain barrier? How is fentanyl metabolised and excreted?
Well- highly lipohilic, highly protein bound
Metabolism: Hepatic - CYP3A4
Elimination: Renally excreted (half-life= 6 mins)
What actions does fentanyl have?
Actions of fentanyl:
- Analgesia
- Anaesthetic
How does fentanyl compare to morphine (in terms of affinity for μ-receptors and side effects)
Affinity:
Higher affinity for μ-receptors
Side effects:
Less:
- Histamine release
- Sedation
- Constipation
What side effects might a patient get from taking fentanyl? (3)
- Respiratory depression
- Constipation
- Vomiting
How is codeine administered?
- PO (Per Os)
- Sub cutaneous
How does codeine work? Why might its effects be different within the population? How is it eliminated?
Codeine–> Morphine via CYP2D6
Varying CYP2D6 in population
CYP2D6 inhibited by Fluoxetine (SSRI)
Eliminated: same way as morphine
Glucoronidation of morphine and renal excretion
What actions does codeine have? How does it differ from morphine in terms of potency?
Codeine= 1/10th potency compared to morphine
Actions:
- Mild-moderate analgesia
- Cough depressant
What are the 2 main side effects of codeine?
- Constipation (give patient laxatives- esp elderly)
- Respiratory depression= worse in children
How is Buprenorphine administered?
Transdermal (patch), buccal, sublingual
= very lipophilic
How is Buprenorphine metabolised and excreted?
Metabolised:
Hepatic- CYP3A4
Glucoronidation
Elimination:
Biliary > Renal
SAFE in renal impairment
half life= 37 hrs
What actions does Buprenorphine have and how does it exert its effects?
Buprenorphine
Actions:
- Moderate-severe pain
- Opioid addiction treatment
Mechanism:
- High affinity for μ-receptor, antagonist at K receptors
- Lower E(max) than morphine (as= partial agonist)
- Long duration of action
Give some of the side effects of Buprenorphine.
- Respiratory depression
- Low BP
- Nausea
- Dizziness
How can Naloxone be administered? What’s its bioavailability like?
Administration:
- IV
- IM
- Intransal
- PO
–> Needs to be given as slow infusion
allow heroin/morphine to metabolise
Bioavailability:
- = very low- extensive FIRST PASS EFFECT
- –> rapid onset of action
- (duration of action= 30-60mins)
How is naloxone metabolised and excreted?
Hepatic–> naloxone-3-glucuronide
Renally excreted
What is naloxone used for?
Used for opioid overdose (reversal agent)
Will dislodge anything at μ receptors (except buprenorphine)
What are the 2 main mechanisms that cause opioid tolerance?
- Phosphorylation and uncoupling
- Repeated exposure
- Intracellular phosphorylation
- Reduced sensitivity of opioid receptor or
- Arrestin proteins bind to receptor instead of g-protein
- cAMP production
- Opioid given= reduces intracellular cAMP
- Opioid withdrawn- cell flooded with cAMP
- ‘Rebound effect’
- Explains withdrawal symptoms- increase neuronal excitability
Who would you need to make special considerations for when prescribing opioids? (8)
Give some contraindications for opioids.
What does PRN mean? (with relation to prescribing)
= pro re nata
= AS NEEDED
Opioids are strictly controlled drugs (under misuse of drugs legislation). What information should you make sure to record if prescribing opioids to a patient?
With opioids- start low and titrate up.
Useful info - most common prescriptions:
