16. Opiate Pharmacology Flashcards
Which neurotransmitter transmits pain?
Substance P
- nociceptors pick up pain signals and they pass through a type A or a type C fibre into dorsal root of spinal cord
- if the gate is open, the signal is transmitted to the thalamus via substance P
- only the stronger signals get through to the primary sensory Cortex
- we have descending pathways which come back down and can inhibit transmission of pain
- opioids act at the level of the spinal cord
What are the 3 classes of endogenous opioid peptides?
1) proenkaphalins: Enkephalins
2) proopiomelanocortin: endorphins
3) prodynorphin: dynorphins
What are the 3 opioid receptors?
Mu: analgesia (euphoria)
delta: analgesia (dysphoria)
kappa: analgesia (sedation)
Note that mu receptors are expressed in lymphocytes as well as the CNS, so opioid can lead to immunosuppression if a patient is on them for a long period of time.
What is the mechanism of action of opiates?
- all opioid receptors are GPCR (Gi)
- they inhibit adenyl cyclase
- decrease cAMP
- causes decreased influx of Ca2+
- reduce neurotransmitter release. (Substance P wont be able to fuse)
- reduce transmission of nociceptive impulses
Note that mu binding, leads to postsynaptic hyperpolarisation (so further from threshold, reducing firing)
Kappa binding reduces presynaptic calcium influx .
What are the indications of use of opioids?
Acute: trauma, burns, perioperative, MI
Chronic: refractory pain, malignancy
Non analgesic: cough suppression, diarrhoea, breathlessness
What are the adverse drug reactions for opioids and which receptor is most often implicated?
The mu receptor whilst being our main target receptor is responsible for most ADRs.
- constipation (nerve complex in the gut is inhibited)
- reduce conscious level
- nausea and vomiting
- respiratory depression
- miosis(constricted pupils)
With kappa can get dysphoria (feeling of confusion)
What is meant by tolerance and by dependence/addiction?
Tolerance: when a patient needs increasing doses of opiate to have an analgesic effect
Dependence/addiction: patient gets withdrawal symptoms on stopping opiates.
Name an opioid agonist and antagonist
Agonist: morphine
Antagonist: naloxone - can be given in toxicity to reverse opiates
Give some examples of some opiates
- Oral codeine: metabolised to morphine (10 x weaker)
- oral tramadol
- morphine -oral tablet or liquid, IV, subcut injection
- fentanyl patch
- oxycodone - often used in cancer pain/renal failure
How do you prescribe controlled drugs?
-need to prescribe in words and numbers specifying the number of vials and tablets required
When deciding regular dose of morphine to prescribe, you add up the amount used in 24hrs PRN + regular and then give in 2 divided doses e.g. if they have taken 5mg of oromorph 6 times in 24 hrs, they would need 30g in a day which can be given as 15mg BD long acting (zomorph) and 5 mg oromorph PRN.
How is morphine metabolised?
- phase 2 metabolism
It is not very lipid soluble so not well absorbed from an oral dose
Metabolites can be measured in urine -screening
What is diamorphine?
Heroin
- crosses the BBB quickly
- gets broken down quickly to morphine by cholinesterase enzymes
- allows us to get a big dose of morphine into the brain quickly
What drug can be used for those with opioid dependency?
methadone
Can stop people injecting. It has a long half life.
What is the ADR for some anaesthetics e.g. fentanyl, alfentanil, remifentanil?
Can cause histamine release and anaphylactic shock
Which opioid can be used as labour analgesia?
Pethidine (IM)
Note that norpethidine is a metabolite of pethidine and can cause convulsions. Do not give frequent repeated doses of this drug as can accumulate in the brain.
