Pharmacology of pain / Flashcards
(30 cards)
Opiates and opioids
Opiates derived from opium - poppies
Opioids have opiate-like effect
What are the different forms of opiates and opioids?
Natural opiates - alkaloids found in opium
Semi-synthetic opiates - synthetic derivatives of natural opiates
Synthetic opioids - synthetic compounds
Opioid peptides - endogenous peptides
What are the principal effects of morphine? (10)
- Analgesia
- Reduced GI motility
- Respiratory depression
- Cough suppression
- Pupil contraction
- Formication (histamine release)
- Nausea/vomiting
- Sedation/anaesthesia
- Euphoria/dysphoria
- Tolerance/dependence/withdrawal
What is the pharmacology (target and activity) of morphine?
Primary target:
mu receptor
Activity: full agonist - high affinity
Secondary target:
k receptor
Activity: partial agonist
Secondary target:
d receptor
Activity: full agonist
What is the physiological action of morphine?
Decreased AC/cAMP/PKA
Decreased Ca2+ channel opening
Increased K+ channel opening
Decrease action potential generation
Decrease axon AP transmission
Decrease NT release
Increased descending inhibition
Decreased ascending transmission
Decreased signal generation
What are the desired effects of morphine?
- Analgesia
- Euphoria
- Anti-diarrhoeal
- Anti-tussive
- Sedation
What are the adverse effects of morphine?
- Respiratory depression
- Nausea/vomiting
- Constipation
- Dependence
What are different opiate receptor subtypes?
mu receptor
kappa receptor
delta receptor
Agonist vs antagonist
Agonist: drug that binds to the receptor and produces similar response to NT/hormone/ligand
Antagonist: drug that binds to the receptor which stops the receptor from producing a response
What is Kd?
Dissociation constant
The concentration of a drug at which 50% of receptors are occupied
What is the general pathway of pain signals from stimulus to motor response?
Noxious stimulus
Impulses sent along afferent fibres towards the CNS, enter the spinal cord. Have cell body in dorsal root ganglion
Efferent fibres have cell bodies in ventral horn.
Impulses sent away from CNS to the peripheral NS - somatic and autonomic > motor response
Pain signals in the peripheral NS
Pain signal generation
Nociceptors - free nerve endings
Ad fibres: sharp/fast/localised
C fibres: dull/slow/diffuse/throbbing
Pain signals in the spinal cord
Pain signal transmission
Spinothalamic tract - pain and temperature
Multiple synapses in dorsal horn - 1st 2nd order
Pain signals in the brain
Pain signal perception
Thalamus - relay centre
Cortex
Limbic system
What are the different nerve tissues?
White matter: myelinated axon tracts. Outside surface of spinal cord
Grey matter: neuronal cell bodies and capillaries. Inner spinal cord, outer surface of cerebellum
Black matter (substantia nigra): modulates movement
What are the different parts of spinal cord grey matter?
Sensory pain fibres terminate and synapse with the dorsal horn
Ad fibres: release glutamate
C fibres: release neuropeptides
Laminae: rexed layers 1-10
Substantia gelatinosa: rexed layer II
Motor fibres originate in ventral horn
Spinal cord white matter
Consists of ascending and descending neural tracts
Pain transmitted in spinothalamic tract:
- Peripheral afferents both Ad and C fibres
- 1 or more synapses in spinal cord
- Fibres cross through the anterior white commissure > contralateral
What pathway is Ad fibres part of?
Impulse sent along 1st order Ad afferent fibre
Neuronal cell body in dorsal root ganglion and synapses in dorsal horn using glutamate as NT, with 2nd order nociceptive neurone
2nd order neurons decussate up the spinothalamic tract and synapses with the thalamus
What pathway are C fibres part of?
Impulses sent along 1st order C fibre, neuronal cell body in dorsal root ganglion. Synapses in dorsal horn. Uses NT substance P
2nd order nociceptive neurone
Most 3rd order nociceptive neurones decussate via anterior white commissure. Ascend in spinothalamic tract. Synapses in thalamus which relays signal to sensory cortex
What are the neuronal pain modulation circuits?
Gate control:
- Non-noxious stimuli can suppress noxious stimuli
- Decrease impulse transmission up spinothalamic tract
Descending inhibitory circuits:
- Descending spinal pathways from CNS can inhibit ascending spinothalamic pathways
- Decrease impulse transmission up spinothalamic tract
Where can neuronal regualtion occur?
Cell body: receptors, NTs, inhibitory/excitatory
Synapse: pre-synaptic receptors, post-synaptic receptors, NTs, inhibitory/excitatory
What are G coupled receptor signalling cycle
G protein heterotrimer is associated with receptor. Ga is bound to GDP
Agonist binding causes exchange of GDP for GTP and dissociation of receptor and a and By subunits
Both a and By subunits can interact with effector molecules to propagate a signal
Intrinsic GTPase activity of the Ga subunit cleaves GTP to GDP bringing the signalling cycle to a close
What is the structure of G proteins?
Form a heterotrimeric complex
Membrane associated
alpha and beta-gamma subunits
What interacts with G proteins?
G protein-coupled receptor (GPCR) interacts with and signals through G proteins
