pain and opioid analgesics

Question 1

pharamcological mechanisms of opioid medicines

Answer 1

• only effective in treating nociceptive pain.
• mainly effective in acute pain, little effect on chronic pain

Noxious peripheral stimuli transmitted in the CNS –> travels to brain to create pain response
- opioids inhibit excitation of transmission neuron –> reduce transmission of pain signals
- inhibit neuropeptide release
- increase descending inhibitory pathways

opioids act on G-coupled protein receptors –> activate potassium release from cells –> hyperpolarisation –> inhibit cell response.
- also inhibit voltage gated calcium channels –> reduced transmitter release

Question 2

opioid adverse effects

Answer 2

CNS effects
o Sedation
o Euphoria
o Changes in mood
o Mental clouding
o Resp depression (resp centre in brain stem)
o Lowers cough reflex
o Nausea and vomiting
o Pupil constriction (effects on oculomotor nucleus)

GI effects- laxative use important!!
o Constipation (due to reduced GI motility and gastric emptying)

Increase histamine release
o Itching or urticaria – use naloxone to reverse opioid effects
o Dilates blood vessels – face flushing
o Hypotension and bradycardia

Genitourinary effects
o Increases smooth muscle tone –> bladder spasms and urgency
Increases urethral sphincter tone –> urinary retention

Immune system effects (long-term opioid use)
o Impair macrophages, natural killer cells and T cells
o Increase risks of pneumonia

Question 3

precautions in opioid use

Answer 3

• epilepsy - increased risk of seizure
• asthmatics or sleep apnoea - hides symptoms, can worsen

Question 4

drug-drug interactions

Answer 4

CNS depressants e.g. benzodiazepines, pregabalin, gabapentin  risk of resp depression, profound sedation or coma

Opioids can lower BP or cause bradycardia – interactions with vasodilators, antihypertensives, BB etc.

Oxycodone metabolised by CYP3A4 – pharmacokinetic interactions e.g. clarithromycin

Question 5

factors affecting opioid dose

Answer 5

Factors affecting opioid dose/application
- weight – does NOT affect dose
- age is main predictor of dose – older patient (>40 years), lower dose (more sensitive to effects)
o increased body fat and reduced total body water  reduced volume of distribution (higher concentrations)
o brain sensitivity increase  increased sensitivity to effects of opioids

Question 6

What can be taken in the event of opioid overdose

Answer 6

naloxone - opioid antagonist

Question 7

Counselling points

Answer 7

• only take medication when you feel pain and for no longer than 3 days
• inform patients of side effects – if drowsy do not drive or operate machinery
• stop taking medication is very sleepy and inform doctor ASAP
• postural hypotension
• increased risk of constipation – increase fluid intake and begin regular laxative use

Question 8

Common opioids - morphine

Answer 8

o metabolism predictable but less predictable than oxycodone – oxycodone preferred
o not recommended in renal impairments
 morphine metabolised by liver, but morphine metabolites are excreted by kidney  renal impairment = build-up of morphine metabolites

Question 9

common opioids - oxycodone

Answer 9

o metabolism is predictable – primarily metabolised by CYP3A4
o commonly used in NSW practice
o synthetic clone of morphine
o immediate release – used PRN for acute pain
o slow release – for chronic pain (delayed onset of action, dose adjustment difficult)

Question 10

common opioids - tramadol

Answer 10

atypical opioid - lower affinity for opioid receptors

o inhibits reuptake of noradrenaline and serotonin  reduced pain response BUT increases serotonin availability by other cells for non-pain related responses
o atypical pathways – not working directly on opiod receptors  reduced adverse effects
o pro-drug – metabolised by CYP2D6 – same issues as codeine
 certain ethnic groups experience too little or too much metabolism of drug
o increased side effects due to additional mode of action (e.g. serotonin toxicity)
o more drug interactions due to mode of action

Question 11

common opioids - tapentadol

Answer 11

o inhibits noradrenaline reuptake  reduced pain response BUT increases serotonin availability by other cells for non-pain related responses
o atypical pathways – not working directly on opioid receptors  reduced adverse effects
o not a pro-drug (is active drug)
o increased side effects due to additional mode of action

Question 12

other opioids

Answer 12

codeine – do not use in renal impairment
o not recommended by therapeutic guidelines
 no good evidence that codeine is more effective than paracetamol or NSAIDs alone or combined
 pro-drug – gets metabolised into morphine by CYP2D6

fentanyl – very potent opioids – increased risk of death

hydromorphone – very potent opioids – increased risk of death

methadone – long half-life

buprenorphine – long half-life