opioids and analgesics Flashcards
1
Q
what is pain
A
unpleasant sensory and emotional experience associated with actual or potential tissue damage
2
Q
what are the stages of the ascending pain pathway
A
- neurotransmitters released by stimuli
- action potential created on the nerve terminal
- this is conducted along the sensory neurone from periphery to spinal neurone
- sodium channels open causing depolarisation
- impulse reaches nerve terminal and nociceptor neurotransmitters are released
- communicated with 2nd order neurone by activating their receptors
- synapse then communicates with 3rd order neurone in cortex
3
Q
what are the fibres in the first order pain afferents
A
- a-delta fibres
- c fibres
4
Q
what is the dull pain pathway called
A
palaeospinothalamic pathway
5
Q
what is the sharp pain pathway called
A
neospinothalamic pathway
6
Q
what are the properties of a fibers
A
- high conduction speed
- transmit proprioception, stretch, touch, pain, mechanical stimuli
7
Q
what are the properties of c fibers
A
- slow conduction speed
- respond to thermal stimuli
- unmyelinated
8
Q
what are the properties of a alpha fibers
A
- myelinated
- proprioception
- fastest a fibre conduction
9
Q
what are the properties of a beta fibres
A
- myelinated
- stretch
- skin touch
- pain
10
Q
what are the properties of a delta fibers
A
- myelinated
- slowest of a fibre conduction
- acute pain and pressure
11
Q
what are the 2 modulations of pain transmission
A
- gate control system
- descending inhibitory neurones
12
Q
how does the gate control system work
A
- sensory stimuli to the spinal cord, primary afferent pathway
- mechanical stimuli to primary afferent
13
Q
how is mechanical stimuli transmitted
A
- stimulate inhibitory interneuron
- these inhibit impulse from higher primary afferent neurones
14
Q
how does the descending inhibitory neurones modulate pain
A
- release inhibitory neurotransmitters
- noradrenaline
- serotonin
- encephalins
- endorphins
15
Q
what is hyperalgesia
A
noxious stimuli pt reacts in a very exaggerated manner
16
Q
what is allodynia
A
a reaction to a non-noxious stimulus
17
Q
what is somatic pain
A
- from skin, skeletal muscle and bone
- due to stimulation of mechanical, thermal or chemical
- well localised
18
Q
what is visceral pain
A
- from injury to viscera
- less localised
- dependent on organ
- referred pain
19
Q
what is neuropathic pain
A
- from damage to pain fibres
- hypersensitivity to stimuli
- persistent perception of pain
- pins and needles
20
Q
how does peripheral sensitisation happen
A
- peripherally released sensitizing agents (PGE, bradykinin)
- activation of signal transduction
- enhancement of ion influx from noxious stimuli
- reduction of activation thresholds of Na channels
- increased sensitivity of peripheral nerve terminal
21
Q
how does a change in sodium channel threshold affect pain sensitsation
A
more easily activated channels means the pain is transmitted faster so you feel the pain faster
22
Q
what is central sensitzation
A
repetitive synaptic transmission that activates intracellular signal transduction cascade that enhances the response to subsequent stimuli
23
Q
how does glutamate affect central sensitisation
A
- activates AMPA-R and NMDA-R
- activation causes depolarisation causing a sodium influx
24
Q
how does the activation of the signal transduction cascade affect centralsenstisation
A
- substance P, NK1 and glutamate trigger the cascade
- causes short and long term sensitisation
25
what are the stages of central sensitsation
1. action potential at primary sensory neuron central terminal
2. ca2+ influx
3. synaptic vesicles released
4. glutamate, substance P and BDNF released
5. triggers activation of signal transduction cascade
5. altered gene expression - long term sensitisation
6. phosphorylation of postsynaptic proteins - short term sensitisation
26
what is the pathophysiology of neuropathic pain
- inflammatory cytokines increase gene transmission of Na channels
- faster pain transmission
- Schwan cells secrete nerve growth factor upregulating gene expression of sodium
27
what happens to the injured nerve fibres in neuropathic pain
- loss of neurotrophic support
- heightened pain sensitivity and continued pain perception
- loss of C fibres allows regenerated Ab fibres which synapse with spinothalamic tract
28
what is the pathophysiology of inflammatory pain
1. damage to phospholipid bilayer
2. arachidonic acid released
3. COX2 site
4. PGG2
5. Peroxidase site
6.PGH2
PGE2
29
how does prostaglandins affect peripheral sensitisation
decreased activation threshold at peripheral terminals or primary afferent nociceptor neurons
30
what are the WHO guidelines on analgesic administration
- oral dosing where possible
- around the clock administration
- prescribed according to pain level
31
TWEED SASH - non pharmacological interventions
psychological
- Therapeutic touch
- Warn about painful interventions
- Explain what is happening
- Establish eye contact
- Defend pt dignity
physical
- Stabilise fracture
- Apply dressing to burns
- Soft surface
- Hypothermia avoidance
32
what is multimodal analgesia
multiple pharmacological agents acting via different mechanisms
33
what are some benefits of using multimodal analgesia
- a synergistic effect
- less incidence of side effect burden
34
fentanyl usage
- trauma
- rapid on set of action
- greater analgesic potency
- less cardiovascular depression lacks unwanted histamine release
- IV, oral, transdermal, intransally
35
what receptors mediate opioids
- mu
- delta
- kappa
36
what do mu receptors mediate in opioids
- analgesia - supraspinal, spinal, peripheral
- respiratory failure
- pupil constriction
- euphoria
- physical dependence
37
what do delta receptors mediate in opioids
- analgesia - spinal
- respiratory failure
38
what doe kappa receptors mediate in opioids
- analgesia - spinal and peripheral
- pupil constriction
- dysphoria and hallucinations
39
what occurs at the supraspinal analgesia with opioids
- release endogenous opioid peptides
- enhance descending pathway
- alter brain perceptions of pain
40
what occurs at the spinal analgesia with opioids
inhibit transmission of nociceptive impulses through the dorsal horn
41
what occurs at the peripheral analgesia with opiods
inhibit discharge of nociceptive afferent terminal in the periphery
42
how do supraspinal analgesia work
- inhibit the descending pathway
- block GABA (morphine)
43
how do spinal analgesia work
1. presynaptic activated - effects calcium influx and calcium blocked
2. vesicle can't release content
3. postsynaptic activated - effects potassium channel by opening it
4. potassium efflux, hyperpolarisation
44
how is codeine metabolised
- into morphine in the liver by CYP enzyme
- then slowly metabolised
45
what are additional mechanisms of action for opioids
block the reuptake in synaptic cleft stopping the action potential (tramadol, tapentadol)
46
what are additional pharmacological actions of opioids
- nausea
- hypotension
- pinpoint pupil
- respiratory depression
- suppression of cough
- euphoria
- bronchoconstriction
- urticaria
- dependency
- tolerance
47
why do opioids cause pinpoint pupils
- stimulation of Edinger-Westphal nucleus of oculomotor nerve
- enhances para-sympathetic stimulation of the eye
48
why do opioids cause respiratory depression
reduce sensitivity of respiratory centre neurones to CO2
49
why do opioids suppress a cough
direct inhibition of cough centre
50
why do opioids cause urticaria and bronchoconstriction
histamine release
51
why do opioids cause nausea
from CTZ stimulation
52
what are opioid contraindications
- acute respiratory failure
- coma
- head trauma
- raised ICP
- paralytic ileus
- biliary colic
53
what CNS depressants do opioids interact with
- alcohol
- benzodiazepines
- z drugs
- MOAI
54
what are the signs and symptoms of opioid overdose
- tachycardia
- hypotension
- respiratory depression
- miosis
- decreased level of consciousness
55
what is the management of opioid overdose
- supportive management eg airway
- IV or IO naloxone every 5 mins
