8. Opiates

Question 1

Describe the ‘pain pathway’.

Answer 1

i. Peripheral nociceptors sense trauma…
ii. AP transmission along peripheral n. C fibres (slow unmyelinated) and A fibres (fast myelinated) which pass through dorsal root of spinal nerve…
iii. synapse in dorsal horn with neurone which ascends in spinothalamic tract…
iv. synapses in thalamus with neurones which extend to primary sensory cortex.

Question 2

Name the 4 main classes of analgesics and their main indications.

Answer 2

1. PARACETAMOL
   - 1st line agent for mild-moderate pain (e.g. headache)
2. NSAIDs (e.g. ibuprofen)
   - mild-moderate pain, esp. MSK related as also anti-inflammatory
3. OPIOIDS (e.g. codeine/morphine)
   - moderate-severe pain, e.g. cancer, chronic, post-op, burn pains
4. NEUROPATHIC AGENTS
   - nerve pain, e.g. diabetic neuropathy, trapped nerves, chronic pain

Question 3

What are the opioid Rs and what is their function?

Answer 3

GPCRs (Gi) located at synapses (e.g. in spinal cord dorsal horn) that act to reduce pain sensation when activated by ligand: inhibit AC… decreases cAMP…

1. on pre-synaptic terminal - reduce Ca2+ influx in response to AP… decreases release of excitatory NT (e.g. glutamate, substance P)
   2. post-synaptic terminal - increase K+ efflux… post-synaptic hyperpolarisation… inhibits neuronal activity

Question 4

name the 3 main opioid Rs and their effects

Answer 4

µ - mu: analgesia (+ euphoria)
δ - delta: analgesia (+ dysphoria)
K - kappa: analgesia (sedation)

Question 5

name the 3 main endogenous opioids

Answer 5

• endorphins
• enkephalins
• dynorphins

Question 6

name acute, chronic and non-analgaesic indications for opioids.

Answer 6

Acute:

• trauma and burns
• perioperative
• MI

Chronic:

• refractory pain
• malignancy

Non-analgesic:

• cough suppression
• manage diarrhoea
• breathlessness

Question 7

Name 6 ADRs of opiates.

Answer 7

1. constipation
2. confusion and reduced conscious level
3. respiratory depression
4. nausea and vomiting
5. constricted pupils

Question 8

Name 2 consequences of long-term opioid use.

Answer 8

1. tolerance: P needs increasing dose of opiate to have same analgesic effect
2. dependence/addition: P gets withdrawal symptoms on stopping opiate

Question 9

Suggest examples of opiate types.

Answer 9

• oral codeine - metabolised to morphine (10x weaker)
• morphine - oral tablet/liquid, IV, SC
• fentanyl - patch
• oxycodone (often used in cancer pain/renal failure)

Question 10

Name an opiate antagonist and its indication.

Answer 10

NALOXONE - opiate overdose/toxicity