8.1 Opioids Flashcards
Define nociception and pain
Nociception: non-conscious neural traffic in response to (potential) trauma
Pain: an unpleasant sensory and emotional experience associated with actual or potential tissue damage (IASP definition)
Describe some of the ‘multidimentional’ aspects of pain
What are the 2 main types of pain and compare these?
1) Nociceptive: caused by an inflammatory or non-inflammatory response to an overt or potentially tissue-damaging stimulus
2) Neuropathic pain: caused by a lesion or disease of the somatosensory NS
Give 4 examples of analgesia
1) Paracetamol
2) NSAIDS
3) Opioids
4) Adjuvants
5) Placebo
Describe the ‘Who analgesic ladder’ for prescribing pain medication
What is the gate control theory of pain?
The gate theory of pain suggests that stimulation of non-nociceptive receptors can inhibit transmission of nociceptive information in the dorsal horn.
Describe the gate theory of pain
1) Afferent 1o sensory neurones of pain are Aδ or C fibres
2) transmission occurs between 1o and 2o neurones in substantia gelatinosa (dorsal horn, spinal cord)
3) Substance P is released at the synaps
4) Inhibition of transmission comes from:
- Inhibitory interneurons linked to Aα and Aβ fibres
- Inhibitory descending pathways from higher brain centres
Describe the pathway of central modulation of pain
Periaqueductal grey matter (PAG) in midbrain ➞ through rostroventromedial medulla (RVM) ➞ into spinal cord
down spinal cord to dorsal horn ➞ releases Serotonin & NA which stimulate interneurons to release Enkephalins, beta-endorphins and/or dynorphin
These bind opioid receptors ➞ inhibits the release of substance P between 1st and 2nd order neurones of nociceptive pathways
Give 3 substances which bind opioid receptors
Give 2 substances which bind non-opioid receptors
Opioid: Enkephalins, beta-endorphins, dynorphin
Non-opioid: Serotonin and noradrenaline
Define the following:
- Opium
- Opiate
- Opiod
Opium: dried powder mixture of 20 alkaloids from unripe seed capsules of the poppy
Opiate: any agent derived from opium
Opioid: substances (exogenous or endogenous) with morphine-like properties
Where do opiods primarily act?
Bind to specific opioid receptors in the CNS (spinal cord) to mimic the action of endogenous peptide neurotransmitters ➞ inhibit the transmission of pain
Give 2 examples of the following opiods:
- natural
- semi-synthetic
- sythetic
Natural: morphine, codeine, papaverine
Semi-synthetic: hydromorphone, hydrocodone, oxycodone, oxymorphone, buprenorphine
Synthetic: fentanyl, fepridine, methadone, tapentadol, tramadol
What class of receptors are opiod receptors + the 4 types
GPCRs ➞ Gi (inhibitory) subtype ➞ located pre and post synaptically
Types:
- μ mu
- δ delta
- κ kappa
- ORL1 (opioid receptor-like 1) (NOP)
Give the MoA of opiods
Gαβγi ➞ Gαi + Gβγi
Pre-synaptic: Gβγi inhibits VOCC ➞ reduces Ca2+ ➞ less NT release
Post-synaptic: Gβγi opens K+ channels ➞ K+ efflux ➞ hyperpolarised + less excitable cells
Give an example of an opiod which is an:
- full agonist
- partial agonist
- antagonist
Agonist: Morphine
Partial agonist: Buprenorphine
Antagonist: Naloxone
What is considered the ‘gold standard’ opiod?
Morphine
Give 4 routes of morphine administration
PO, IM, IV, SC, nebulized, rectal, epidural, intrathecal
Morphine is a PCA, what does this mean?
patient controlled analgesic
Describe morphines absorption in the gut and 1st/2nd pass metabolism
Well absorbed from the gut and undergoes extensive first-pass metabolism (oral bioavailability ~25%)
Give the 2 metabolites of morphine and state their clinical relevance
Metabolites: morphine-6-glucuronide and morphine-3-glucuronide
Metabolites can be measured in urine, useful for screening
Give the chemical name and common name of Diamorphine?
Chemical: Diacetyl morphine
Common: Heroin
Diamorphine undergoes a _______ reaction to form the intermediate _______. This is then converted into morphine.
hydrolysis, monoacetyl morphine
Compare the t1/2 of diamorphine and morphine
Diamorphine: t1/2 = 5mins
Morphine: t1/2 = 4 hours
Codeine is a _____ opioid at the ____ receptor hence has mild analgesic properties (oral). It is metbaolised in the body to ______ by the CYP______ enzymes and can therfore be affected by polymorphisms in this cytochrome class.
weak, mu, morphine, CYP2D6
Codeine acts as an effective analgesia in what region of the CNS
spinal and supraspinal level
How does codeine cause sedation and euphoria
Effect on midbrain dopaminergic, serotoninergic and noradrenergic nuceli
What effect does codeine have on bowel movements?
Decrease in motility, increase smooth muscle tone (constipation)
Why does codeine cause depression of cough reflex?
Codeine and morphine have antitussive properties
???
What 3 opioid drugs are commonly used in anaesthetics?
What is a common ADR of these?
Fentanyl, alfentanil, remifentanil
ADR: can cause histamine release
Which analgesia is commonly used in labour?
Why should it NOT be given in frequent repeated doses?
Pethidine (IM)
Frequent doses can cause accumulation of metabolite which can lead to convulsions
(Pethidine ➞ norpethidine (metabolite) ➞ convulsions)
Why do opiods cause repiratory depression?
There are μ receptors in the respiratory-centre of the brain stem ➞ hypercapnic drive
Why can opiods cause nausea and vomiting?
Central effect on chemoreceptors trigger zone in medulla
Why may opiods cause constipation
Increased SM tone and decreased motility ➞ spasm of sphincter of Oddi ➞ constipation
How may opiods cause bradycardia and hypotension?
Bradycardia: decreased SNS drive + direct effect on SAN
Hypotension: Histamine release ➞ decrease TPR and reduced baroreceptor reflex
Why may opiods cause pruritis?
Histamine release from mast cells
Hallucinations are most common with which opiods?
k agonists (but morphine and other μ agonists may also cause hallucinations)
Why may Miosis be seen with opiod use?
μ and κ receptors in occulomotor nerve are stimulated by opioids resulting in constriction of the pupils
Give 2 other undesirable symptoms experienced with opiod use?
Drowsiness and Dysphoria
Why can opiod use lead to dependence/tolerance?
Down regulation of opioid receptors or decreased production of endogenous opioids
Describe the legal requirements for prescribing controlled drugs?
