Clinical Use of Analgesics: Opioids and Other Medicines Flashcards
What is the mechanism of action of opioids?
Spinal level:
- Inhibits transmission of nociceptive signals through dorsal horn and spinal reflexes
- Inhibiting adenyl cyclase and thus decreasing cAMP
- Closure of VGCCs (less Glu release)
- Opening of K+ channels (cell hyperpolarisation)
Supraspinal:
- Inhibits descending signals to brainstem and spinal cord
Which opioids are used for moderate and severe pain respectively?
Moderate pain:
- Codeine
- Dihydrocodeine
- Dextropropoxyphene
Severe pain:
- Morphine
- Diamorphine
- Oxycodone
- Fentanyl
- Tramadol
When are opioids used for severe pain?
- Acute pain
- Persistent non-cancer pain
- Palliative care
- No ceiling effect; restricted by side effects
What are the common side effects of opioids?
- Nausea & vomiting (40% of patients will experience)
- Constipation (reduced GI motility)
- Sedation
- Respiratory depression (bronchoconstriction as less sensitvity to pCO2 in respiratory centre)
- Hypotension
- Urinary retention
What are the less common side effects of opioids?
- Narcotic bowel syndrome
- Immunosuppression
- Endocrine dysfunction
- Addiction
How is opioid-induced constipation treated?
Non-pharmacological:
- Diet (high fibre)
- Fluids
Laxatives:
- Stimulant laxative (Senna) in combination with stool softener (Lactulose)
Peripherally restricted opioid antagonist:
- Methylnaltrexone (SC administration)
- Naloxone PR (in Targinact)
How is oral morphine treatment initiated for pain?
- Pain assessment inc. current analgesia
- Determine opioid requirement: use short-acting preparation regularly, plus PRN dosing
- Calculate 24 hour requirements
- Convert to MR formulation e.g. MST, Zomorph
- 1/10 to 1/6 of total daily dose prescribed every 4 hours for breakthrough pain
What is the procedure to change a patient onto an alternative opioid?
- Determine 24 hr requirement
- Use conversion factor for alternative opiate to determine new 24 hr requirement
- Convert to appropriate dosing regimen
What is PCA and what opioids are involved?
- Patient can dose themselves up if analgesia required (bolus dosing)
- Morphine is drug of choice
- Tramadol, oxycodone or fentanyl used if morphine allergy
What are the advantages of PCA?
- Rapid analgesia once pain at steady state (Css)
- Ready prepared
- Patient satisfaction
- No dose delay
- Patient acceptability
- No peaks or troughs
What are the disadvantages of PCA?
- Expensive
- Requires IV access
- Training
- Monitoring
When are epidurals used and what is entailed? Which drugs are used?
- Alternative to PCA esp. in maternity, lower limb, spinal or abdominal surgery
- Mixture of LA and opioid (synergistic action)
- Fentanyl + bupivacaine (or levobupivacaine)
What are the adverse effects associated with epidural use?
Why is respiratory depression not a concern?
- Hypotension
- ‘Wrong route’
- Infection
+ Respiratory depression uncommon due to lipophilicity of fentanyl
What are syringe drivers and the indications for its use?
- Continuous SC infusion
Indications:
- Nil by mouth e.g. N&V, dysphagia
- Bowel obstruction
- Patient does not wish to take regular medication by mouth
What is the drug of choice for syringe drivers and why?
- Diamorphine
- Excellent aqueous solubility
What other drugs are mixed in with diamorphine for syringe drivers and the indications?
- Haloperidol, cyclizine (N&V)
- Levomepromazine, midazolam (restlessness & confusion)
- Midazolam (seizures)
- Hyoscine N-butylbromide (excessive respiratory secretions)
What is monitored during opioid therapy?
- Pulse
- BP
- RR
- Pain
- Oxygen saturation
- Sedation score
- Opioid usage
- Opioid side effects
What is naloxone and how is it given?
- Opioid antagonist
- Higher affinity of opioid receptor than agonist (used in overdose etc)
- Short T1/2 when given IV (thus repeated doses may be necessary)
- May induce pain (knocking off opioid agonists)
- Titrate gradually until effect achieved
What is tramadol and how does it work?
- μ-opioid receptor agonist (30% of analgesic affect; metabolised into more potent opioid agonist, O-Desmethyltramadol)
- This is formed from CYP2D6 metabolism like morphine from codeine; ceiling-effect in those lacking this enzyme
- Inhibits NA reuptake and releases 5-HT (inhibits that reuptake too?)
- More tolerable opioid side effect profile (e.g. less incidence of constipation)
- Potentially more pronounced N&V though
Which tricyclic antidepressants are used for neuropathic pain and how do they work?
- Amitriptyline, nortriptyline
- Inhibits neuronal reuptake of NA and 5-HT
How are tricyclic antidepressants implemented dosage-wise and why?
- Use limited by adverse effects
- Adverse effects minimised by starting with low dose and small incremental changes
How are antiepileptic drugs effective for neuropathic pain? Name some.
- They block VGSCs (stabilise the inactive state) in peripheral neurones
- BUT high incidence of adverse effects thus limited license for neuropathic pain
E.g. carbamazepine, phenytoin, sodium valproate
How are anticonvulsants effective for neuropathic pain? Name two.
- Prevent VGCC activation (as well as NMDA interaction/enhancing descending noradrenergic pain control)
- No effect on VGSCs
- Fewer adverse effects and drug interactions than epileptics like carbamazepine
- Licensed for neuropathic pain
How is capsaicin used for analgesia?
- TRPV1 receptor agonist
- Licensed for post-herpetic neuralgia (PHN)
- Counselling on application required (use EMLA)
