(PM3B) Pain & Analgesia Flashcards
What are the components of pain?
(1) Sensory
(2) Emotional
Hence why it is subjective
What are some different methods to rate pain?
(1) Numeric rating scale
- 1-10
- functional scale
(2) Visual analogue scale
- No pain to worst possible pain
(3) Verbal Pain Intensity Scale
- for young/ disabled patients
- no pain to unimaginable/ unspeakable pain
- also a 1-10 scale
What do the different numbers (1-5) of a functional pain scale correspond to?
0 = no pain
1 = tolerable + pain does not prevent activities
2 = tolerable + pain prevents some activities
3 = Intolerable + pain does not prevent use of phone/ TV/ reading
4 = Intolerable + pain prevents use of phone/ TV/ reading
5 = Intolerable + pain prevents verbal communication
What is the purpose of acute pain?
Protective mechanism
e.g. thermal burns
What are the types of pain?
(1) Nociceptive pain
(2) Neuropathic pain
What type of pain is caused by a tissue injury?
Nociceptive pain
How long does acute nociceptive pain last?
<3-6 months
Desirable
How long does chronic nociceptive pain last?
> 6 months
Undesirable
What is allodynia?
Pain after stimulation
Not normally painful
What is hyperalgesia?
Increased pain from a stimulus that normally causes pain
What is neuropathic pain?
Nerve injury
What are some conditions that are associated with neuropathic pain?
(1) Diabetic neuropathy
(2) Phantom limb pain
(3) Cancer pain
(4) Chemotherapy-induced peripheral neuropathy
(5) Postherapeutic neuralgia
How may neuropathic pain be described?
(1) Severe
(2) Sharp
(3) Burning
(4) Cold
(5) Numb
(6) Tingling
(7) Weakness
What is the pain pathway?
(1) Detection of pain in the periphery
(2) Transmission of pain signals from periphery to spinal cord
(3) Reception of signal by higher central brain centres
Describe the role of local neuronal circuits and descending inhibitory pathways from higher brain centres.
Signals are amplified or inhibited
Describe the myelination state of non-nociceptive Aß.
Myelinated
Describe the myelination state of nociceptive C.
Unmyelinated
What sensation do non-nociceptive Aß fibres produce?
Touch + pressure
What sensation do nociceptive C fibres produce?
Dull + burning pain
What sensation do nociceptive A-delta produce?
Sharp pain
What is the gate control theory of pain?
Melzack + Wall’s theory
Inhibitory interneurons in spinal cord control incoming sensory information before it’s transmitted to the brain
(1) Activation of C/ A-∂ fibres open gate (increased pain)
- direct excitation of gate OR inhibition of SG interneurons
(2) SG interneurons inhibit
- close the gate
- reduce pain
(3) Activation of Aß fibres close gate by excitation of Sg interneurons
(4) Descending inhibitory pathways from CNS close gate
- inhibit the gate OR direct activation of SG interneurons
What are some inflammatory mediators of peripheral pain?
(1) Bradykinin
(2) Substance P
(3) ATP
(4) Protons
(5) Prostaglandins
- particularly PGE2 + PGF2
What is the role of bradykinin as an inflammatory mediator of peripheral pain?
Activates B2 receptors in nociceptive neurones + B1 receptors via a metabolite
What is the role of substance P as an inflammatory mediator of peripheral pain?
Activates NKA (neurokinin) receptors in nociceptive neurones
What is the role of ATP as an inflammatory mediator of peripheral pain?
Activates P2X3 receptors
What is the role of protons (H+) as an inflammatory mediator of peripheral pain?
Activate acid-sensing ion channels (ASICs)
What is the role of prostaglandins as an inflammatory mediator of peripheral pain?
PGE2 + PGF2
Greatly increase responses to bradykinin and 5-HT
Increase sensitisation
What are prostanoids?
Prostaglandins + thromboxane
Produced from precursors in cell membrane
What are some important neurotransmitters in hyperalgesia?
(1) Glutamate
- acts at AMPA to mediate acute pain
- acts at NMDA receptors (delayed)
(2) Substance P
- acts at NK1 receptors
- enhances NMDA action (hypersensitivity)
(3) Nitric oxide
- enhances further transmission of pain signal
What factor limits non-opioids?
Ceiling effect
Dose above which there is no further pharmacological action
What is the mechanism of action of opiates?
Increase descending inhibitory pathways
Decrease neuropeptide release
What is acetylsalicylic acid?
Aspirin
Which analgesic is most appropriate for dysmenorrhoea?
Aspirin
Give some examples of indoles.
(1) Diclofenac
(2) Indomethacin
Give some examples of propionic acid derivatives.
(1) Ibuprofen
(2) Naproxen
(3) Ketoprofen
What is etoricoxib licensed for?
(1) Ankylosing spondylitis
(2) Osteoarthritis
(3) Rheumatoid arthritis
(4) Acute gout
What is celecoxib licensed for?
(1) Ankylosing spondylitis
(2) Osteoarthritis
(3) Rheumatoid arthritis
Why were rofecoxib and valdecoxib withdrawn?
Cardiovascular side effects
Why was lumiracoxib withdrawn?
Hepatotoxicity problems
What is nefopam?
Non-opioid
For persistent pain if NSAIDs or opioids are not suitable
Causes little-no respiratory depression
Can have sympathomimetic + antimuscarinic side effects
What is paracetamol?
Non-opioid
Reduces the production of prostaglandins in CNS
For which type of pain are NSAIDs and opioids most effective?
Nociceptive pain
How is neuropathic pain most commonly treated?
(1) Anti-epileptics
(2) Tricyclic antidepressants
What are some anti-epileptics used to treat neuropathic pain?
(1) Sodium channel blockers
- Carbamazepine
- Phenytoin
(2) via effects on Calcium channels
- gabapentin
- pregabalin
What are some tricyclic antidepressants used to treat neuropathic pain?
(1) Duloxetine (SSRI/ SNRI)
(2) Imipramine/ amitriptyline
- for diabetic neuropathy
Name some less commonly used drugs to treat neuropathic pain.
(1) Ketamine
- binds to NMDA receptor
(2) Lidocaine/ bupivacaine
- blocks sodium channels
(3) Ziconotide
- new generation calcium channel blockers
- administered intrathecally
(4) Cannabinoid agonists
- e.g. sativex
- for multiple sclerosis
(5) Botulinum toxin
- reduces muscular hyperactivity
What are opioids?
Highly effective analgesic
Act spinally + supraspinally
Produce analgesia in mild-moderate pain
Is morphine an agonist/ antagonist?
Agonist
Is naloxone an agonist/ antagonist?
Antagonist
Is methadone an agonist/ antagonist?
Agonist
Is pethidine an agonist/ antagonist?
Agonist
What are the different opioid receptors?
(1) M-receptor
(2) ∂-receptor
(3) k-receptor
(4) ORL1-receptor
Which drugs bind to the ORL1-receptor?
None
Endogenous opioid peptide (nociceptin) only
To which opioid receptor does morphine bind?
M-receptor
To which opioid receptor does fentanyl bind?
M-receptor
To which opioid receptor does buprenorphine bind?
k-receptor
Which endogenous opioid peptides bind to the opioid M-receptor?
(1) ß-endorphin
(2) enkephalin
Which endogenous opioid peptides bind to the opioid ∂-receptor?
(1) Met-enkephalin
(2) Leu-enkephalin
Which endogenous opioid peptides bind to the opioid k-receptor?
(1) dynorphin A
(2) dynorphin B
Describe the supra-spinal action of opioid-induced analgesia.
(1) Opioid action at µ (∂ + k) receptors
(2) Enhances descending inhibitory pathway in brain
(3) Involves noradrenaline + serotonin (5-HT) release
(4) via GABA inhibition
Describe the spinal action of opioid-induced analgesia.
(1) Activation of pre-synaptic receptors
- µ > ∂
(2) Reduces transmitter release
Where do opioid agonists act?
All at µ receptors
Except pentazocine
- k agonist
What is morphine?
Gold-standard to which all opioids are compared
Metabolised to potent analgesic morphine-6-glucuronide
IV or PO as morphine sulphate tablets (MST)
What do fentanyl, alfentanil, sufentanil, and remifentanil have in common?
Opioid agonists
Very potent
Short-duration
Often as a transdermal patch
What is oxycodone?
Opioid agonist
Primarily used for control of pain in palliative care
What is pethidine?
Opioid agonist
Used during labour
- due to lack of effect on uterine contraction
What is codeine?
Opioid agonist
Low efficacy + orally effective
Not addictive
Causes constipation with long-term use
What is dihydrocodeine?
Opioid agonist
Similar efficacy to codeine
Can cause more nausea + vomiting
What is diamorphine (heroin)?
Opioid agonist
Metabolised to morphine
High lipid solubility
- leads to rapid action
Higher efficacy
What do tramadol and tapentadol have in common?
Opioid agonist
Weak opioids
Inhibitors of noradrenaline uptake/ transport system
What is buprenorphine?
Partial opioid agonist
Long duration
Can be given sublingually
What are some common side effects of opioid agonist use?
(1) Euphoria
(2) Respiratory depression
(3) Cough suppression
(4) Nausea
(5) Constipation
What is euphoria, with relation to opioid use?
Common side effect of opioid agonist use
Action on reward pathway
- increases dopamine release
k-agonists (pentazocine) causes dysphoria
- nightmares
- hallucinations
What is respiratory depression, with relation to opioid use?
Common side effect of opioid agonist use
Reduced sensitivity of respiratory centre
Most common cause of death from overdose
Treated with naloxone
What is cough suppression, with relation to opioid use?
Common side effect of opioid agonist use
Anti-tussive effect
Can be therapeutically useful
What is nausea, with relation to opioid use?
Common side effect of opioid agonist use
Activation of chemoreceptor trigger zone
- in turn activates vomiting centre
Treated with anti-emetics
What is constipation, with relation to opioid use?
Common side effect of opioid agonist use
Due to maintained contraction of smooth muscle
What is the neuropathic pain ladder?
(1) TCA/ SNRI/ voltage-gated calcium channel subunit ligand
- TCA = amitryptyline
- SNRI = duloxetine
- voltage-gated calcium channel ligand = pregabalin/ gabapentin
(2) Consider tramadol or capsaicin cream
- or add SNRI if not already used in first line
What is the nociceptive (analgesic) pain ladder?
(1) Non-opioid/ NSAID
(2) Weak opioid for mild-moderate pain (e.g. codeine) + non-opioid + adjuvant
(3) Strong opioid for moderate-severe pain (e.g. morphine) + non-opioid + adjuvant
