Opioids Flashcards
What is the difference between pain and noniception?
Nociception- non-conscious neural traffic due to trauma and potential trauma to tissue (heat removal).
Pain- complex, unpleasant awareness of sensation modified by experience, expectation, immediate context and culture. Doesn’t need tissue damage, sensation is from the somatosensory cortex.
What stimulates nociceptors?
Tissue damage - release serotonin, bradykinin and prostaglandin.
How is pain stimulated?
Nociceptors stimulated, release substance P and glutamate.
Afferent nerve stimulated - in the dorsal horn (lamina 1-5), A delta fibres - myelinated sharp pain
C fibres - unmyelinated, dull ache.
Send action potentials via the spinothalamic tract.
Pain can be modulated by what central and peripheral centres?
Peripheral- substantia gelatinosa
Central - peri-aqueductal grey
How can pain be modulated peripheral?
Tissue damage stimulates A delta and C fibres which stimulate the thalamus and inhibit the substantia gelatinosa (allowing pain to reach the thalamus).
By “rubbing it better” the substantia gelatinosa is stimulated, inhibiting lamina 1-5 (which is stimulated by pain) and then reducing projections to the thalamus.
How can pain be modulated centrally?
Stimulatory fibres to both the thalamus and cortex, stimulate the periaqueductal grey matter and cause inhibitory fibres to release serotonin and enkephalins to the dorsal horn.
These stimulate the endogenous opioids and prevent pain from being perceived.
What type of receptor do endogenous opioids act at?
GPCR
Mu, delta and kappa
What is the major effects of stimulating opioid receptors?
Decrease cAMP and cause hyperpolarisation, decreasing substance P release and increase dopamine release.
Where are the 3 types of opioid receptors found and what are they stimulated by?
MOP- supraspinal/GIT, enkephalins and b-endorphins
DOP-wide distribution, enkephalins
KOP- spinal cord, brain, periphery- dynorphins
What are the main principles of opioids as a class?
Exploit receptors either agonising or antagonising
Main therapeutic effect is via Mu receptors
Aim to modulate pain
Also indicted in cough, diarrhoea and palliation
Give an example of a strong agonist
Morphine or fentanyl
What is the action of morphine?
Strong affinity and complete activation of Mu receptors.
Minimal affinity for KOP and DOP.
Causes analgesia and euphoria
What are the side effects of morphine?
Respiratory depression - medulla less responsive to Co2
Emesis- stimulate chemoreceptor zone
GIT- decrease motility and increase sphincter tone
Cardiovascular - hypotension and syncope
Miosis
Histamine release -itchy (caution in asthmatics)
Why might fentanyl be used instead of morphine?
100 times more potent and higher affinity for Mu receptor.
Less histamine release, sedation and constipation.
Reduced side effects; respiratory depression, constipation and emesis.
Act as a analgesic and anaesthetic
Name a moderate agonist and its mechanism of action
Codeine
1/10th potency of morphine, with a mild to moderate analgesic effect and cough depressant.
What side effects must be considered in giving codeine and which patient groups should be prescribed something else?
Side effects: constipation and respiratory depression, worse in children.
Since codeine is metabolised by CYP2D6 into morphine, those who are on fluoxetine and other SSRIs may not experience analgesic effects due to inhibition of the enzyme by SSRIs.
Name an opioid with a mixed effect and its main uses
Buprenophine
Moderate to severe pain and opioid addiction treatment.
Compared to morphine, buprenorphine…
Has very high affinity for MOP receptor, with low Kd.
Long duration of action and not easily displaced.
Lower EMax as a partial agonist, lower efficacy.
Antagonist at KOP.
What are the common side effects of buprenorphine?
Respiratory depression
Low BP
Nausea
Dizziness
Name an opioid antagonist and its effectiveness in comparison to morphine.
Naloxone - used for overdoses
Greater affinity than morphine, but less than buprenorphine.
Affinity MOP>DOP>KOP
What are the problems with giving naloxone?
Short half life and slow infusion
How might a patient develop opioid tolerance?
Phosphorylation and uncoupling
CAMP production.
What groups of patients should be under special considerations when prescribing opioids?
Manual labourer/driver Elderly Bed bound Asthmatics Biliary tract obstruction Respiratory disease Renal impairment Pregnancy
What are the contraindications of opioids?
Hepatic failure Acute respiratory distress Comatose Head injuries Raised ICP
