Opioid Pharmacology Flashcards
How is 50% of oral morphine metabolised
First pass metabolism in the liver
What does 50% metabolism of morphine mean for prescription
We have to double the dose (10mg morphine = 5mg really)
How long does a single dose of morphine last
3-4 hours
How often is morphine given for ‘slow release’ palliative care
Twice a day
Benefits of diamorphine vs morphone
Diamorphine is more potent and passes across blood-brain barrier more quickly
What class are opioids categorised as
Class A drugs
Why are opioids difficult to get a hold of
- Secure storage
2. CD (controlled drug) books need two signatures
Dihydrocodeine vs codeine
1.5 x more powerful
How do opioids work physiologically
- Inhibits release of pain transmitters at spinal cord and midbrain by binding to G-coupled receptors
- Modulate pain perception at higher centres and emotional response
What two hormones do opioids inhibit to bring bout decreased pain perception
Natural endorphins
Enkephalins
How do Opioids work
Descending inhibition of pain
Do opioids bring about sustained activation
No
What is the problem of sustained activation due to opioids
Leads to tolerance and addiction
Name of the four receptors
MOP
KOP
DOP
NOP
What do Kappa morphine receptors do which is different to the other three
Causes depression instead of euphoria
What receptor do all drugs currently act on
M(u) receptors
Define Potency
How well the drug binds to the receptor
Define efficacy
How well receptor is activated
Which is more potent, Morphine or Diamorphine
Morphine (10mg) vs Diamorphine (5mg for same effect)
Why does Tolerance occur
Down-regulation of receptors with prolonged use
Need higher doses to reach same effect
Define dependance
Psychological response to tolerance - craving
When does opioid withdrawal take place
24 hours and lasts 72 hours
Where else can opioid receptors be found other than the pain system
- Digestive tract
2. Respiratory control centre
Side effects of opioids
- Sedation
- Nausea
- Constipation
- Itching
- Immune Suppression
- Endocrine Effects
Why do we start with a small dose of opioids and titrate up
Because different patients have a range of sensitivity to opioids
How do we treat Opioid induced respiratory depression
ABC
Naxolone IV via titration (remember patient sensitivity)
What do we have to be aware of when giving Naxolone to drug addicts in A&E
Short half-life of naxolone
Ho do we titrate Naxolone
Dilute 1ml in 10 ml of saline
What is the issue with opioid use in Chronic non-cancer pain
They are losing effectiveness quickly
More deaths than US traffic accidents and firearms
What is the results of opioid addiction on patient
Easy to start and difficult to get them off it
What kind of drug is codeine
Prodrug
What enzyme metabolises Codeine
CYP2D6
How doe genetics effect Codeine metabolism
CYP2D6 activity is decreased in 10-25% of white population and absent in a further 10% so codeine has a reduced effect in this population
CYP2D6 is overactive in 5% of whites so increased risk of respiratory depression
What is Morphine metabolised to
morphine-6-glucuronide
How is Morphine-6-Glucuronide excreted
Kidneys
Potency of morphine-6-glucuronide vs morphine
Morphine is less potent
How do we give morphine to patients with 30%< renal function
Reduce dose and timing interval
OR use oxycodone instead as it is safer
What is Tramadol
Weak opioid agonist
Potency of TRamadol vs Codeine
Stronger in Tramadol
What type of drug is Codeine and what metabolises it
Prodrug
Metabolised by CYP2D6
End-product of Tramadol metabolism
O-desmethyl tramadol
Secondary effect of Tramadol
In analgesia (serotonin and nor-adrenaline reuptake inhibitor)
What and why do we take care with Tramadol prescription to people with antidepressants
Interacts with SSRIs, antidepressants and MAOs fatally
How much of the population can’t metabolise morphine
10%
What is diamorphine also known as
Heroin
Three synthetic opioids
Pethidine
Fentanyl (potent)
Alfentanil (potent)
What happens if we overdose on Buprenorphine
No respiratory depression
Fastest mode of administration of opioids
IV takes 1 minute to travel round the whole body
How long does it take for morphine to reach the brain
5 minutes
How is does self-administered by patients with analgesia
Every 5 minutes with lockout
Why is salt-administration for analgesia safe
Patient will sleep before onset of respiratory depression
How long do opioids have an effect for
30 minutes
Potency of Pethidine vs Morphine
10 times weaker
Why does Buprenorphine only reach 50% response rates
Only a partial agonist (safer)
How does mixing Morphine with Naloxone effect efficacy of morphine
Reduces it
Why do we mix morphine and Naloxone
To correct an overdose
How does continued morphine use effect Mu receptors
Desensitises them
