Opioids Flashcards
Define pain. (3)
A complex, unpleasant awareness of sensation modified by the brain and affected by experience, expectation, context and culture.
Define nociception (2)
A non-conscious reflex prompted by trauma to tissue.
Describe the path that pain takes from the tissue to the brain. (9)
Nociceptors stimulated, releasing substance P and Glutamate
Afferent nerves stimulated (A(delta) fibres for sharp, C fibres for dull)
Spinothalamic tract followed, so fibres deccusate
Action potential ascends and synapses in the thalamus
Projects to the post-central (sensory) gyrus.
Describe how we peripherally modulate pain. (5)
“Rubbing it better” prompts the inhibition of the A(delta) and C fibres in the substantia gelatinosa through A(beta) fibres. This reduces the pain signals transmitted to the thalamus.
Describe how we centrally modulate pain. (2)
Periaqueductal grey matter (nose and mouth of Mickey Mouse in the brainstem).
Name three types of endogenous opioids. (3)
Encephalins
Dynorphins
Beta-endorphins
Describe the receptors that endogenous opioids act on. (4)
All GPCRs
Encephalins - DOP (delta)
Dynorphins - KOP (kappa)
Beta-endorphins - MOP (mew)
Describe the distribution of the receptors that endogenous opioids act on. (3)
Encephalins - widely distributed
Dynorphins - spinal cord / brain.
Beta-endorphins - GI tract
Describe what stimulating the receptors of endogenous opioids leads to. (2)
All leads to a decrease in cAMP release.
Describe the result of the stimulation of receptors for endogenous opioids. (3)
Encephalins - influx of calcium
Dynorphins - influx of calcium, efflux of potassium.
Beta-endorphins - efflux of potassium
Describe what the movement of ions prompted by endogenous opioids causes. (3)
Hyperpolarisation and decreased substance P release, to decrease nociceptor response.
Describe what each effect endogenous opioid has on the body. (12)
Encephalins - analgesia, dopamine inhibition, modulating mew receptors.
Dynorphins - analgesia, dysphoria, diuresis
Beta-endorphins - analgesia, dependence, euphoria, respiratory sedation, depression.
Describe the WHO analgesia ladder for chronic use of painkillers. (5)
Simple analgesia eg NSAIDs / paracetamol.
Weak opioid eg codeine
Strong opioid eg morphine / fentanyl
Describe the MoA and aims of opioid therapy. (4)
Exploit the natural mew receptors through agonism or antagonism.
Aim is to modulate pain, but also used in cough, diarrhoea, and palliation.
Name 6 strong agonists of the mew receptors. (6)
Morphine Fentanyl Heroin (diamorphine) Methadone Oxycodone Oxymorphone
Name one moderate agonist of the mew receptor. (1)
Codeine
Name one mixed agonist / antagonist of the mew receptor (1)
Buprenorphine
Name two antagonists of the mew receptor (2)
Naloxone
Naltrexone
Name one opioid that does not agonise or antagonise the mew receptor. (1)
Tramadol.
Describe the pharmacokinetics of morphine. (5)
Most commonly given IV or SC; can be given oral but bioavailability low (40%) and absorption erratic.
Rapidly enteral all tissues inc foetal
Struggles to cross the BBB - no high
Eliminated renally coupled with glucuronic acid.
Describe the actions of morphine on receptors and it’s effects on the body. (3)
Complete action on mew, little effect on delta or kappa.
Causes analgesia and euphoria.
Describe the side effects of morphine use. (5)
Respiratory depression
Emesis (direct CTZ trigger)
Decreased GI motility
Contraindicated in CKD because renally excreted.
Histamine release - caution in asthmatics
Describe the pharmacokinetics of fentanyl. (9)
Given IV, epidurally, nasal, with 90% bioavailability.
Highly lipophilicity, high protein binding, high levels of CNS crossing.
Hepatic metabolism by CYP3A4
t1/2 of 6 mins, renally excreted (but more safe in CKD than morphine)
Describe the advantages of prescribing fentanyl over morphine. (4)
Fentanyl is safer in CKD
Fentanyl is 100x more potent than morphine
Fentanyl has less severe side effects - less histamine release, less sedation, less constipation.
Describe the actions of fentanyl. (2)
Analgesia
Anaesthetics
Describe the side effects of fentanyl. (3)
Respiratory depression
Constipation
Vomiting
Describe the pharmacokinetics of codeine. (4)
PO most common, SC also available.
Codeine metabolised to morphine by CYP2D6.
Excreted by the glucoronidation of morphine and renal excretion.
Explain why codeine can have different levels of effectiveness in different people. (3)
Because it is metabolised to morphine by CYP2D6 and this can exhibit polymorphism between people.
Explain why codiene should not be taken by those on Prozac. (3)
Prozac is fluoxetine the antidepressant.
It inhibits CYP2D6 causing codeine to build up in the body.
Describe the difference in potency between morphine and codeine. (1)
Codeine is 1/10th as potent.
Describe the actions of codeine. (2)
Mild to moderate analgesia
Cough depressant
Describe the side effects of codeine. (2)
Consitpation
Respiratory depression, esp in children.
Describe the pharmacokinetics of buprenorphine. (6)
Given in transdermal patches.
Very lipophilicity.
Hepatic metabolism through CYP3A4 then glucoronidation before biliary excretion.
t1/2 = 37 hours.
Explain why buprenorphine is safe in renal disease. (1)
Because it is excreted through the biliary system, so won’t affect the kidneys at all.
Explain why buprenorphine can be used to treat pain in a morphine addiction. (4)
Has a higher affinity for mew receptor that morphine, so will displace it and will not be displaced easily. However, because it’s an agonist still, will still give pain relief.
Describe the side effects of buprenorphine. (4)
Respiratory depression (still there but less severe)
Hypotension
Nausea and dizziness
Doesn’t prevent opioid withdrawal.
Describe the pharmacokinetics of naloxone. (5)
IV, intranasal or PO (rare due to low bioavailability)
Very lipophilic
Hepatic metabolism, t1/2 very short, but duration of action is 30-60 minutes.
Excreted renally.
Describe the affinity of naloxone for the receptors. Compare its affinity to morphine and buprenorphine. (2)
Kappa < delta < mew
Morphine < naloxone < buprenorphine
Describe the most common use got naloxone and explain the method of administration in this case. (5)
Commonly used in acute opioid overdose, because will displace morphine from the receptor. Must be given as a slow infusion because the t1/2 is so small, that an hour after it’s given, it will all dissociate and the morphine will rebind. This will cause the patient to collapse in the car park.
Explain why opioid tolerance occurs. (4)
When exogenous opioids are given, receptors are upregulated mean you need a higher dose over time to get the same response. This is what causes withdrawal, because once synthetic opioids are removed, endogenous opioids aren’t near to enough to get a response.
Explain the point of methadone therapy. (2)
It binds to the excess receptors to reduce withdrawal effects.
Describe the treatments of an opioid overdose. (3)
Delta agonists
5HT3 agonists
Naloxone infusion
Describe the commonest cause of death in opioid overdose. (2)
Respiratory depression due to mew receptor overload.
Describe and explain the special considerations that must be made when prescribing opioids. (12)
Manual labourours / drivers - sedative effects dangerous
Elderly - lower Vd - doses reduced
Asthmatics - don’t want to reduce resp drive
Biliary tract obstruction - can’t excrete buprenorphine.
Renal impairment - can’t excrete anything but buprenorphine.
Pregnancy - addiction or respiratory distress in the newborn.
Describe the contraindications of opioids. (3)
Hepatic or renal failure
Head injury
Acute respiratory distress
Describe the commonest presentation in palliative care that prompts the prescription of morphine. Explain why. (3)
Pain and short of breath.
Relieves pain and respiratory depression will relieve the SOB.
Describe the way of working out the BD dose and the PRN dose of opioids in palliative care. Give an example if the patient is taking 120mg per day and this is enough. (3)
Work out how much drug needed in one day for good control of pain eg 120mg
BD dose = total / 2 = 60mg
PRN dose = total / 6 = 20mg
Describe why codeine can be difficult to manage if the dose needs to be upped. (2)
Often comes with paracetamol, so cant up the dose without going over paracetamol limits. Change tablet form.
