PH3113 - Pain and Analgesia 5 Flashcards
How should an opioid overdose be treated?
Critical aspect of overdose is respiratory depression
Nalaxone
- very rapid
- very effective
- precipitates sudden and violent withdrawal
- may increase dependent state
- short half life
- repeated administration required
- relapse will occur
Neutral antagonists
- 6b-naltrexol cross Blood-Brain Barrier
- manage overdose better
- slightly slower effects
- less withdrawal effects
Give examples of opioid antagonists
Nalorphine
- partial agonist
Pentazocine
- partial agonist
Naloxone
- antagonist
Buprenorphine
- partial agonist
What is opioid hyperalgesia?
Opioids elicit paradoxical increase in ‘pain’ in animals and humans
- hyperalgesia or allodynia noted in different area to original pain
Methadone maintenance patients are susceptible to hyperalgesia
Hyperalgesia may normally be masked by concurrent analgesia actions
- different mechanisms
- different time course
Give examples of chronic pain resistant to traditional analgesics
Nerve entrapment
Post-traumatic pain
- fractures
- amputation
- stump
- neuroma formation
- referred pain
- phantom pain
Neuralgia
- nerve fibres fire randomly
- trigeminal
- post-herpetic
Chronic low back/neck pain
- post-traumatic
- rheumatic
- post-operative
Cancer
Spasticity
Causalgias
- burning pain
- nerve derangement following trauma
Vascular insufficiencies
Perineal pain
- late onset
- unrelieved sitting
Give examples of pain syndromes
Musculoskeletal imbalance syndrome
- physiotherapy
Growing pains
Localised idiopathic pain/complex regional pain syndromes
Diffuse idiopathic pain
- rheumatisms
- fibromyalgia/idiopathic myalgias
What is neurogenic inflammation?
Substance P and CGRP released from primary nociceptive afferents
- C fibres
Act in the periphery to promote inflammation via their effects on blood vessels and cells of the immune system
This amplifies and sustains the inflammatory response
It may also involve central facilitation leading to pathological hyperalgesia
Give three examples of neuropathic pain
Hyperalgesia
- increased pain to a mildly noxious stimulus
- central facilitation
- peripheral sensitisation
Allodynia
- pain to a non-noxious stimulus
Spontaneous pain
- pain without stimulus
What is central facilitation/wind up of pain?
Repeated stimulation increases the amplitude of the action potential
- NMDA glutamate receptors
Prevented by
- NSAIDs
- reduce peripheral stimulation
- spinal cord opioid antagonists
- reversed with NMDA antagonists in the spinal cord
What is the role of NMDA in wind-up and treatment?
Short depolarisation
- no release of Mg2+ block
Long depolarisation
- release of Mg2+ block
- Ca2+ flux
What are the targets for analgesia?
PAG
- GABA and glutamate
Nucleus raphe magnus
- 5-HT
What is the relationship between 5-HT and pain?
Complex bidirectional role of 5-HT transmission at spinal level
Inhibitory transmitter of inhibitory neurones linking the nucleus raphe magnus and dorsal horne
- midbrain
- descending pathway
Noxious stimuli increase 5-HT turnover in spine
- ascending pathway
5-HT3 receptors implicated in Nefopam and acetominophen action
- blockade activates descending inhibitory pathways
- may be key in allodynia and hyperalgesia
5-HT7 may mediate opiate analgesia
What are the three principles of general anaesthetics?
Loss of conscious awareness
Loss of response to noxious stimuli
Reversibility
What are the sites of action for anaesthetics?
Interaction at INHIBITORY neurotransmitter channels
- GABA(A)
- Glycine
Interaction at EXCITATORY neurotransmitter channels
- NMDA
- nicotinic
Which substances can bind at the GABA(A) receptor?
Binding sites for GABA associated with the alpha-subunit
Modulatory sites
- alpha/gamma interface
- benzodiazepines
- beta
- etomidate
- thiopentone
- propofol
- volatiles
What are the properties of the Glycine receptor?
Major inhibitory neurotransmitter
- chloride channel
- volatile anaesthetics all potentiate the actions of glycine
