Pharmacology of Pain Flashcards
Which spinal tract sends information about nociception? [1]
Where does the first synapse of this spinal tract occur? [1]
Lateral spinothalamic tract
First synapse is the dorsal horn at the spinal level: target for targets of pain control
Which types of pain respond well [1] and not well [1] to analgesiacs?
Nociceptive: analgesics
Neuropathic: responds poorly to analgesics
Desribe the pathway of the lateral spinothalamic tract [3]
First-order neurones”
- cell bodies are in the dorsal root ganglion whose axons extend from peripheral receptors
Second-order neurones
- cross almost immediately via the anterior spinal commissure and form the lateral spinothalamic tract
- Then ascends in the lateral funiculus. Fibres of this tract are somatotopically organised for their entire course.
Third-order VPL neurons:
- send axons through the posterior limb of the internal capsule to the somatosensory cortex (areas 3, 1, 2).
What are the potential targets that occur at dorsal horn to treat nociceptive pain?
- cyclooxygenase-2 (COX-2)
- nitric oxide synthase (NOS)
- glutamate receptors (NMDA and non-NMDA type)
- neurokinin 1 (NK1) receptors,
- opioid receptors (e.g. μ receptors)
Why is the dorsal horn horn a useful place to treat pain? [1]
Can target without having to cross the BBB [1]
Explain why pain is an indivuadual experience [6]
Pain is influenced by the folowing factors, which work on an individual basis:
Cognition: attention; distraction; control
Context: beliefts; expectations; placebo
Genetics
Injury: peripheral and central sensitisation
Chemical and structural dopaminergic dysfunction
Mood: depression; anxiety
How are endogneous opioids rapidly inactivated when in circulation? [1]
Peptides are rapidly inactivated by peptidases in the circulation
What are the types of opioid receptor types [3] and subtypes [8]
Mu opioid receptors (µ1, µ2, µ3)
Delta opioid receptors (δ1, δ2)
Kappa opioid receptors: (κ1, κ2 ,κ3)
Which familiy is the primary opioid receptor for analgesia? [1]
What are potential AEs of using this family? [1]
Mu family
AEs include respiratory depression; reduced GI motility; dependence
Where are Mu opioid receptors found in the body? [1]
All over of the body: why broad spectrum of AEs occurs
Works at supraspinal and spinal level
Explain the MoA of morphine [4]
- Mu acts on receptors (e.g. Mu)
- Causes activation of K+ conductance and decreased calcium conductance
- This leads to decreased excitability (K+) and decreased release of neurotransmitters (Ca2+).
Name the drug that reverses overdoses [1]
State the MoA [1]
Naloxone: opiate antagonist
Why may you need to give multple doses of naloxone for an opioid overdose? [1]
Opioids often have long half lifes, whilst naloxone has a very short half life
Asides from morphine, name 5 other opioids prescribed
- Herion: high solubility compared to morphine
- Dextromoramide: potent but limited prescription
- Methadone: large half-life - so used for long dosing.
- Meptazinol: Mu-1 produces less respiratory depression than morphine
What do you need to consider about tolerance and addiction to opioid prescription [2]
- Tolerance isn’t a major problem in the context of chronic pain or terminal illness
Tolerance is a natural process and a different pathway to the development of addiction
(Generally advised not to under-dose because of fear of tolerance. But be careful) dosing.
