Opioids Flashcards
What are the two broad actions of opioids?
Central effects
Psychoactive
If you are in a better mood, not as bothered by pain
Peripheral effects
Gate theory
Summarise how opioids exert their effect vie the gate theory?
Pain transmission is mediated by the substantia gelatinosa
The neurotransmitter used in Substance P
Opioid drugs inhibit the release of substance P from nerve terminals
There are also inhibitory descending pathways from higher centres in the brain
What are some endogenous opioid peptides?
Enkaphalins (from proenkaphalin) (DOP)
Endorphins (from pro-opiomelanocortin (POMC)) (MOP)
Dynorphins (from prodynorphin) (KOP)
What are the different types of opioid receptors?
μ mu (MOP)
δ delta (DOP)
κ kappa (KOP)
How are the opioid receptors distributed?
mu - analgesia (supraspinal)
kappa - analgesia (spinal cord)
delta - Enkaphalins (widely distributed)
Pre- and post-synaptic expression
What is the mechanism of action of the opioid receptors?
mu (MOP) binding
Increased outward flux of K+
\/Leads to\/
Decreased excitability
kappa (KOP) binding
Decreased influx of Ca2+ via channels
delta (DOP)
Decreased cAMP synthesis
All these are GPCRs
They all lead to a decreased amount of intracellular Ca2+
And so a decreased release of neurotransmitter
What are some of the ADRs of opioids?
mu (MOP)
- Nausea/vomiting
- Constipation
- Drowsiness
- Miosis (excessive constriction of the pupil of the eye)
RESPIRATORY DEPRESSION (monitoring required) Hypotension
Dependence
Tolerance
kappa - dysphoria (confusion) (pentazocine)
Give examples of the different actions some opioid drugs can have.
Agonist e.g. morphine Partial agonist e.g. buprenorphine Agonist/antagonist e.g. nalbuphine - (Agonist at one receptor, antagonist at another) Antagonist e.g. naloxone
Name some opioid analgesics.
Morphine (T1/2=1.3-6.7hrs) (Oral bioavailability=25%) Diamorphine (T1/2=0.08hrs) Methadone (T1/2=15-30hrs) (Oral bioavailability=90%) Buprenorphine Codeine Dihydrocodeine Fentanyl Pethidine Nalbuphine Tramadol
Tell me about morphine.
Gold standard opioid analgesic
Metabolism: glucuronidation to
morphine-6-glucuronide
and
morphine-3-glucuronide
Metabolites can be measured in urine
Tell me about Diamorphine.
It is a good way to deliver morphine to the brain
It has a half life of 5 mins
Then hydrolysed to monoacetyl morphine
Then to morphine
What are the clinical uses of some opioids?
Analgesic
- relief of moderate to severe pain (particularly of visceral
origin)
Morphine - analgesic (terminal illness) (diarrhoea)
Diamorphine - analgesic (terminal illness)
(Can be used as an epidural analgesic but not licensed)
Methadone - maintenance in dependence
Tramadol - analgesic (5-HT and NA effects)
Tapentadol - analgesic (specific mu agonist, NA reuptake inhibitor)
Anaesthetics Fentanyl Alfentanil Remifentanil (ADR: can cause histamine release)
Pethidine - analgesia in labour (im)
(BUT be careful, metabolite causes convulsions)
(DO NOT GIVE frequent repeat doses)
Tell me about Codeine.
Mild analgesic (oral)
Metabolised to morphine
By CYP2D6
(So polymorphisms in CYP2D6 can cause changes in codeine metabolism)
Name some opioid agonists-antagonists.
All are used as analgesics
Pentazocine
Nalbuphine
Butorphanol
Buprenorphine
Meptazinol
Name some opioid antagonists and their uses.
mu receptor antagonists
Naloxone (T1/2 = 1-1.5hrs)
Naltrexone (T1/2 = 4hrs (oral))
Uses:
Opioid toxicity
Reverse respiratory depression
Treatment of dependence
