Opioids Flashcards
What is the WwHO analgesic ladder?
The WHO analgesic ladder tells us what we should use depending on the severity of the pain.
Starts at simple analgesia such as: paracetamol sand NSAIDS
In the middle there is desk opioid use is: codeine
And at the end of the spectrum there is strong opioid use such as: morphine and fentanyl, these don’t work for everyone/everything, they are best for acute, severe pain both malignant and non malignant.
Tends to be for chronic patients, as you want to try and reduce the strength and dose of the painkillers.
How does morphine work?
Morphine has a strong affinity for mu receptors, the binding blocks the transmission of nociceptive signals, it activates the signalling of pain modulating neurones in the spinal cord and inhibits the transmission from primary afferent nociceptors to the dorsal horn sensory projection cells.
What ate the side effects of morphine?
Respiratory depression (causes the resp centres to be less responsive to CO2)
Emesis (stimulates the chemoreceptor trigger zone)
GI tract (constipation), decrease in motility and increase in sphincter tone
Cardiovascular affects
Miosis
Histamine release (caution in asthmatics)
What is the best way to give morphine?
IV
Only 40% oral bioavailability
Gut absorption is erratic
What is the difference between nociception and pain?
Nociception is a reflex which we have, to stop ourselves from being hurt ie: pulling your hand away from something hot.
Pain: it is complex, experience you feel which is modified by your
Sensation interpretated by the brain, which doesn’t necessarily have tissue damage associated with it, it is modified by previous experience, context and culture.
So what is the sequence of pain?
So you will get tissue damage which release inflammatory mediators like cytokines etc…
this stimulates nociceptors
Then you get release of substance P and glutamate
The afferent nerves are stimulated by the glutamate, (the substance P acts locally)
The fibres decussate
The action potential ascends and synapse in the thalamus which then project to post central gyrus (sensory cortex)
What are the pain fibres?
A delta fibres Give you the initial sharp pain that makes you pull your hand away
C fibres are responsible for the dull, throbbing pain.
How can we modulate pain?
So we have peripheral system and central system modulators..
peripherally= substantia Gelatinosa
Centrally= peri aquaduct all grey
How do we modulate pain?
Well peripherally fibres from the tissue damage A alpha and Laminar C also inhibit the substantia Gelatinosa which prevents us from modulating pain.
How do we modulate pain centrally?
Generally periaqueductal grey matter, is under inhibition from the cortex, but when we get a pain response, the pain can act on thalamus which then acts on the periaqueductal grey matter which then sends inhibitory fibres which reduces the release of endogenous opioids ie: enkephalins.
Why is morphine really useful?
Because you can have it in many ways! If you have a kid with pain you can still give as you can give it PO.
Why do you have to be careful with patients taking morphine who have CKD?
It is eliminated regally, therefore can get toxic levels.
When is fentanyl used?
Used in surgical settings
Why is fentanyl a really good drug?
It has an 80-100% bioavailability
It can be given IV, epidural, intrathecal, nasal
It has a good distribution- it is highly protein bound and highly lipophilic so can get into many body tissues!
Has a high level of CNS crossing
It is renally excreted however less so than morphine therefore less harmful in patients with AKD.
How is fentanyl metabolised?
Hepatic via CYP3A4
