Opioids Flashcards
What are the 3 major groups of endogenous opioids?
Endorphins
Encephalins
Dynorphins
What are the 3 major types of opioid receptor?
Mu (MOP)
Delta (DOP)
Kappa (KOP)
Where are Mu opioid receptors found?
Hence why can long-term opioid use lead to immune suppression
Mainly in brain but also on surface of B cells - hence long term use can lead to immune suppression
In broad terms, what is the mechanism of action of opioids?
Central effects - psychoactive - produce “dissociation” from pain
Peripheral effects - inhibit release of substance P preventing transmission of pain from dorsal horn to thalamus
At the molecular level, what is the mechanism of action of opioids?
Opioid receptors are GPCRs - Gi type
Opioid binding:
- Increases efflux of K+ - reduced cell excitability as hyperpolarised
- Decrease influx of Ca2+
- Decreased cAMP synthesis, which further decreases Ca2+ influx
- Decreased Ca2+ leads to reduced vesicular fusion with surface membrane, hence reduction of substance P NT release
Give 4 common ADRs associated with opioid use
Give a serious ADR associated with opioid use
- Constipation
- Nausea
- Vomiting
- Drowsiness
- Respiratory depression
What is the benefit of partial agonist/antagonist opioids?
Analgesic without causing euphoria - non-addictive
What is Naloxone? How does it work?
Opioid Mu receptor antagonist - used to reverse opioid overdose
What is the problem with Naloxone?
Half-life shorter than morphine’s - effect wears off before Morphine’s so must be given repeatedly
How is morphine given best?
Why?
Best IV as low bioavailability - 25%
How is morphine metabolised?
Straight into phase II metabolism - undergoes glucaronidation
Forms soluble metabolites which can be screened for in the urine
What is diamorphine also known as?
Heroin
What is special about diamorphine’s action?
Highly lipophilic so crosses the BBB very rapidly.
Half-life only 5 minutes in brain - immediately hydrolysed to morphine, hence very good for giving a large dose of morphine very quickly
What is important about Methadone’s PK?
Highly protein-bound - 90%
Why does Codeine not work in many of the population?
Prodrug - activated by CYP2D6 which are highly polymorphic - no effect in those lacking enzymes.
