Opioid Analgesics Flashcards
What type of receptors are opioid receptors. How do they function?
Opioid receptors are inhibitory G-protein coupled receptors.
Opioid agonists bind to receptor and cause inhibition of neurotransmitter release.
What are the three major classes of opioid receptors
- Mu
- Kappa
- Delta
What effects do µ opioid receptors mediate? (5)
- Analgesia
- Euphoria
- Respiratory depression
- Bradycardia
- Reduced gut motility
Describe the locations of opioid receptors and their role in the effects seen with opioid use.
CNS
Brain
- Brain stem = analgesia
- Limbic system = abuse, addiction
- Cortex
Dorsal horn of spinal cord
- Presynaptic = analgesia
- Postsynaptic
PNS
- Nociceptive fibres expressed after injury
Which receptor does morphine act on?
µ-receptor agonist.
How are opioids dosed?
Titrated to effect - minimise life-threatening adverse effects such as respiratory depression.
Describe the metabolism/excretion and mechanism of action of morphine
Metabolised in the liver to morphine-3-gluconoride and morphine-6-gluconoride.
Morphine-6-gluconoride is the active compound, producing analgesic effect.
Metabolites are renally excreted.
What are the indications and contraindications to morphine use?
Indications:
- Moderate to severe acute pain
- Palliative care
- Pre-operative analgesic
Contraindications:
- Hepatic / Renal failure
Compare codeine to morphine
Codeine is a pro-drug:
- Demethylated to morphine
- CYP2D6 enzyme
Codeine is 10x LESS potent than morphine.
Describe the two types of genetics defects to be wary of when administering codeine?
- Approx 10% of patients lack the enzyme to convert codeine.
- Small % of people are ‘rapid metabolisers’ and can incur adverse effects at normal doses.
Indications of codeine use:
- Mild to moderate acute pain
- Antitussive (cough suppressant)
Compare the bioavailability of morphine and codeine
Morphine has a low bioavailability of 35% - mostly used IV.
Codeine has good bioavailability.
Side effects of opioid use, regardless of strength
- Nausea and vomiting
- Constipation
Name the synthetic µ-opioid receptor agonist
Oxycodone.
What level of pain is oxycodone good for?
Moderate to severe pain relief.
WHat are teh three types of oral preparations of oxycodone?
- Immediate release oxycodone (Oxynorm)
- Controlled release oxycodone (Oxycontin)
- Controlled release oxycodone with naloxone (Targin)
Addition of naloxone (opioid antagonist) = reduced opioid induced constipation and protects from abuse.
What is tramadol?
An atypical centrally acting analgesic.
Mechanism of action of tramadol?
Metabolised in the liver to active metabolite
- Agonist to µ-opioid receptor
- Serotonin reuptake inhibitor
- Noradrenaline reuptake inhibitor
Effects of tramadol, compared to morphine.
In equi-analgesic doses to morphine, tramadol has:
- Less respiratory depression
- Less constipation
Serotonergic effects:
- Nausea, vomiting, confusion
- Interaction with other serotonergic drugs (SSRIs, TCAs)
Contraindication to using tramadol?
Due to its interaction with other serotonergic drugs, it lowers seizure threshold
- AVOID in epilepsy.
Uses for tramadol:
Useful in avoiding adverse effects of opioids:
- Respiratory depression
- Tolerance and dependence
- Constipation
Can be used in neuropathic pain treatment.
Uses for methadone?
Good in neuropathic pain - NMDA antagonist effect.
Major use is opioid replacement in addiction.
Why are opioids not ideal for chronic pain relief?
Development of tolerance - all opioid antagonists.
- Around 2 weeks with morphine
Describe how opioid withdrawal can occur, and what are the symptoms?
Occurs with:
- Abrupt discontinuation
- Administration of antagonist
Symptoms of withdrawal:
- Nausea, vomiting, diarrhoea
- Anorexia
- Sweating, shivering, anxiety
