PHARM - Drugs for Pain Management - Week 9 Flashcards
Define pain.
Unpleasant sensory and emotional experience associated with actual or potential tissue damage
What is the vital purpose of pain?
Serves as a defence function
Is pain objective or subjective?
It is a uniquely individual and subjective exerience
List the two kinds of acute pain and list two properties for each.
Somatic
-sharp
-well localised
Visceral
-dull
-poorly localised
Do a significant number of individuals live with constant chronic pain or is it rare?
Common - 1 in 5 for Australia
Are current evidence-based treatments of chronic pain under- or over-utilised? Explain.
Under-utilised.
<10% of people with chronic non-cancer pain gain access to care that could allow up to 80% to be treated effectively.
What period of time is chronic persistent pain considered to be?
> 3 months
List the three broad groups of chronic persistent pain and give an example of each.
Defined nociceptive basis
-cancer
Well-defined neuropathological basis
-peripheral neuropathy
Idiopathic
-chronic musculoskeletal pain
Describe the kind of pain felt by the following classifications:
Superficial somatic (3)
Deep somatic (2)
Visceral (2)
Neuropathic (5)
Superficial somatic - hot, burning, stinging
Deep somatic - dull, aching
Visceral - dull, deep
Neuropathic - pins/needles, tingling, burning, shooting, phantom pain
Briefly describe, in 5 steps, the nociceptive curcuit for pain.
Activation of the peripheral terminal by a noxious stimulus
It is conducted to the dorsal horn of the spinal cord
Dorsal horn relays the signal to the CNS
Signal passes through brainstem areas, the thalamus, to the cortex of the brain
Signal descends along a modulatory control pathway
What are the three kinds of sensory events that can activate a nociceptive neuron? Can all the receptors be activated by a single event or are there specific receptors for specific events?
Thermal, chemical, and mechanical
Each one activates a specific peripheral receptor
What three pieces of information can frequency and duration of an action potential by a nociceptor transfer to the CNS?
Onset
Intensity
Duration
Describe the two inhibitory regulations that can occur to the spinal cord.
Local inhibitory interneurons
Projections that descend from the brainstem to the dorsal horn
Name 5 major inhibitory neurotransmitters in the dorsal horn.
Opioid peptides
Noradrenaline
5-HT
Glycine
GABA
Consider acute pain severity. Describe the pharmacological treatment for mild (1), moderate (3), and severe (4) score ratings.
Mild - paracetamol
Moderate - paracetamol ± an NSAID ± oral opioid
Severe - as in moderate with an increased dose of oral opioid ± i.v./s.c. opioid or fentanyl patch
What are opiate substances derived from?
Opium poppy
What are the two naturally occuring opioid compounds in opium poppy?
Morphine and codeine
What are endogenous opioid peptides called?
Endorphins
What are endorphins, where are they made, and what molecule does it have similar activity to?
Neurotransmitter and hormone peptides made in the brain that acts similar to morphine
Aside from the brain, where else are endorphins made and released?
Gastrointestinal tract
List two roles of endorphins.
Analgaesia - inhibit pain neurotransmission/perception of pain
Regulation of intestinal motility
Can endorphins be absorbed from the gut? What happens to them? Do they pass the blood-brain barrier? Are they useful therapeutic agents?
Not absorbed by the gut.
Rapidly metabolised and cannot pass the blood-brain barrier.
Not useful as therapeutic agents.
What are the receptors for opioids, what effect do they elicit, and in what two areas of the body are they dense?
Can they be found in peripheral tissues or na?
μ Opioid Gi-coupled GPCRs
They elicit analgaesia
Dense in the brain and spinal cord
Can also be found in peripheral tissues
Consider peripheral nerve transmission for pain. Keeping whether opioid receptors are present peripherally or not, describe the effect μ-opioid agonists would have on this transmission.
Opioid receptors are found peripherally, and so agonists to these receptors would inhibit peripheral pain transmission.
Consider a peripheral pain signal being conducted to the dorsal horn of the spinal cord. What effect would a μ-opioid receptor agonist have on this process?
No effect.
Consider a pain signal at the dorsal horn. What effect would a μ-opioid receptor agonist have here?
An agonist would inhibit the activity of relay neurons.
Consider a pain signal passing through brainstem areas, the thalamus, and to the cortex of the brain. What effect would a μ-opioid receptor agonist have here?
No effect.
Consider the descending modulatory control pathway. What effect would a μ-opioid receptor agonist have here?
They enhance descending inhibition
Describe the pre-synaptic mechanism of action of a μ-opioid receptor agonist (2).
Inhibits Ca2+ influx
-decreases neurotransmitter release
Describe the post-synaptic mechanism of action of a μ-opioid receptor agonist (3).
Increases K+ conductance, leading to hyperpolarisation, and decreased post-synaptic response to excitatory neurotransmission
Name three effects of morphine.
Analgaesia
Euphoria
Less emotional response to pain