Opioid Analgesics Flashcards
(42 cards)
What are the best defined peptides?
- opioid peptides e.g. β-endorphin, met/leo-enkephalin and dynorphin
- substance P
What is substance P?
mediator of slow EPSPs in nociceptive CNS sensory pathways
What are the 3 major families of endogenous opioid peptides and their precursors?
- β-endorphin from pre-proopiomelanocortin (POMC)
- enkephalins from pre-proenkephalin
- dynorphins from pre-prodynorphin
What can influence the perception of pain?
attitude, mood and physical exercise
What parts of the brain process and interpret pain signals?
thalamus and cortex
What does the limbic system influence?
the emotional response of pain, often generating feelings of discomfort, anxiety, or distress
How does opioid analgesia work?
it plays on endogenous mechanisms to inhibit the propagation of pain signals, alter the emotional perception of pain and elevate the pain threshold
What are opioid analgesics used for?
- acute pain e.g. post-surgical pain
- chronic pain management, particularly for cancer-related pain or palliative care
What are the 3 main sites of opioid receptors regulating pain?
- peripheral nociceptive terminals
- spinal cord (dorsal horn)
- brain (PAG, thalamus and cortex)
What are the 3 major opioid GPCRs and what are they responsible for?
- mu – analgesic effects and side effects like euphoria, respiratory depression, and physical dependence
- delta – modulates pain and mood, and has a role in analgesia (less than mu receptor); may also influence antidepressant effects
- kappa – modulates pain, but activation can also produce dysphoria and hallucinations; plays a role in the body’s response to stress and controls some anti-inflammatory effects
How do opioids inhibit neurotransmitter release?
- inhibiting calcium entry
- enhancing potassium efflux
- inhibiting AC which converts ATP to cAMP
How does opioid analgesia cause euphoria?
they bind to Mu receptors in the VTA and nucleus accumbens and inhibit the release of GABA, which leads to an increase in dopamine levels in reward circuits
What is dopamine a precursor of?
noradrenaline
When is dopamine inhibitory?
via GPCR activation of potassium channels
How is dopamine activity increased and decreased respectively?
- increased by CNS stimulants and anti-parkinson drugs
- decreased by antipsychotics
What is D2?
the main dopamine subtype in basal ganglia neurons widely distributed at the supraspinal level
Give examples of dopaminergic pathways
- nigrostriatal (motor control)
- mesolimbic (emotional and drug-induced reward systems)
- tuberoinfundibular tracts (pathway from hypothalamus to pituitary glands that controls secretions)
What are clinical uses of opioid agonists?
- analgesia e.g. codeine, morphine, pethidine
- anaesthetic adjuvant e.g. fentanyl
- cough suppressant/antitussive e.g. codeine
- anti-diarrhoeal e.g. diphenoxylate, loperamide
Describe morphine as an opioid agonist (strength, which receptors, analgesic affinity and liability for abuse)
- strong agonist
- highest affinity for Mu receptor (some affinity for Delta and Kappa)
- high maximum analgesic affinity
- high liability for addiction/abuse
Describe methadone and fentanyl as opioid agonists (strength, which receptors)
- strong agonists
- highest affinity for Mu receptor (no affinity for Delta and Kappa)
What is fentanyl used as?
an anaesthetic adjuvant
Describe codeine as an opioid agonist (strength, which receptors, analgesic affinity and liability for abuse)
- moderate agonist
- weak affinity for Mu and Delta receptors
- low maximum analgesic affinity
- moderate liability for addiction/abuse
What happens to 10% of codeine?
it is converted to morphine/dihydromorphine
Why do 10% of the population show reduced analgesic effects to codeine?
lack of demethylating enzyme
