pain and opioid pharmacology Flashcards
name a naturally occurring opioid
from the opium poppy ->
morphine
codeine (weaker)
name a synthesised opioid
fentanyl - made to have faster onset time
heroin aka. diamorphine
what is the antidote to opioids?
naloxone
what are routes of administration for opioids ?
oral - need x2 as IV (50% bioavaibabilty)
IM
IV -fastest, can use patient controlled analgesia (patient presses button for more from IV)
lollipops
what class drugs are opioids?
class A
how do opioids reduce pain ?
they use the existing pain modulation system
inhibit the release of pain transmitters at spinal cord and midbrain – and modulate pain perception in higher centers – euphoria – changes the emotional perception of pain
Block it with release of endorphins and enkephalins (pleasurable. euphoric hormones)
which pain pathway do opioids act on?
Descending inhibition of pain
are opioids designed for short term or long term pain relief?
designed for short term pain relief
Sustained activation leads to tolerance and addiction through Downregulation of receptors
how soon does opioid withdraw start?
within 24 hours
why are there some side effects of opioids, not to do with pain relief ?
Opioid receptors exist outside the pain system e.g. digestive tract, respiratory control centre
we tend to administer them systemically eg. IV therefore they affect the whole body
list examples of side effects of opioids
Respiratory depression
Sedation
Nausea and vomiting
Constipation
Itching
Immune suppression
Endocrine effects
how is respiratory depression caused by morphine?
Morphine is metabolized to morphine 6 glucuronide which is more potent than morphine and is renally excreted.
With normal renal function this is cleared quickly
In renal failure it will build up and may cause respiratory depression
advice for prescribing opioids
*Before prescribing opioids, discuss with the patient the risks and features of tolerance, dependence, and addiction - use short term courses
Agree a treatment strategy and plan for end of treatment
Warnings have been added to the drug labels and packaging of opioids to support patient awareness
At the end of treatment, taper dosage slowly to reduce the risk of withdrawal effects - may take weeks
why does different dosages of codeine affect people differently?
Codeine is a prodrug - it needs to be metabolised by cytochrome CYP2D6 into morphine to work
CYP2D6 activity varies in patients
should you prescribe codeine for non-cancerous pain?
explain why
no - it loses affect quickly (tolerance builds to pain relief) and is very addictive
what is the WHO pain ladder?
simplistic way to rate pain intensity .
There are 3 rungs to the ladder, corresponding to increasing pain intensity.
The clinician prescribes medications as pain worsens, moving from one rung to the next.
what are the 3 rungs to the pain ladder?
1) anti-inflammatory agents, for mild pain
2) weak opioids, for mild - moderate pain
3) strong opioids for moderate to severe pain
define pain
an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage.
what are current opinions on the WHO pain ladder?
nowadays seen as outdated, hasn’t been updated eg. does not include fixed dose combination analgesics in step 2.
need to add a 4th sept for very severe pain
general pain pathway - how many neurones are involved?
3 orders of neurones
these carry action potentials signalling pain
what do first order neurones do in the pain pathway?
reaches from peripherals (detects pain) to spinal cord (cells bodies within the dorsal root ganglion.)
what do 2nd order neurones do in the pain pathway?
decussates to contralateral cord and ascends in the spinothalamic tract to the ventral posterolateral nucleus of the thalamus
what do 3rd order neurones do in the pain pathway?
thalamus to midbrain & higher cortical centres (primary sensory cortex)
what are the specialist receptors that 1st order neurones have to detect pain?
Nociceptors
found at free nerve endings of primary afferent neurones
what are the different types of Nociceptors?
mechanical - distention and pressure
chemical
thermal
polymodal - chemical, mechanical and thermal
opioid receptors - how do they work and produce analgesia
G protein-coupled receptors
their activation leads to a reduction in neurotransmitter release and cell hyperpolarisation,
reducing cell excitability.
what are the 3 types of endogenous opioids (body already contains them)
exogenous = morphine etc.
Β-endorphins
Dynorphins
Enkephalins
define first pass metabolism
rapid uptake and metabolism of an agent into inactive compounds by the liver, immediately after enteric absorption and before it reaches the systemic circulation
i.e. concentration of the drug is greatly reduced before it reaches systemic circulation.
explain why oral morphine has a bioavailability of 50%
ie. the oral dose is 10mg, the IM dose is 5mg
if given orally, is has to undergo first pass metabolism
it is metabolised by the intestine and liver before reaching try systemic circulation
if a patient has renal impairment, any morphine should be given in lower doses and in longer intervals
why is this the case?
Morphine is metabolised in the liver to morphine 6 glucuronide which is more potent than morphine.
morphine 6 glucuronide is then excreted by the kidneys
if a patient has renal failure it will not be as readily excreted. risk of the potent morphine building up therefore prescribe them lower doses
define acute pain
pain for less than 12 weeks
define chronic pain
continuous over 12 weeks, the pain persists beyond the tissue healing time
what is the difference between somatic and visceral pain ?
Somatic = pain of the muscles, bones, soft tissues
Visceral = pain of the internal organs
what is thalamic pain
burning pain
caused by damage to thalamus in stroke
what is neuropathic pain
damage to nerves causing spontaneous pain (shooting,burning,pins and needles feeling)
or evoked pain by stimulus that shouldnt produce pain normally eg. touching something cold
what is psychosomatic pain
pain lacking a medical explanation eg. caused by stress
what is referred pain
when the pain you feel in one part of your body is actually caused by pain or injury in another part of your body. Eg. an injured pancreas could be causing pain in your back,
what is Illusionary pain
an illusion, disconnected from reality
define hyperalgesia
enhanced sensation of pain at normal threshold stimulation
Define allodynia
pain experienced in response to a stimulus that was previously not painful.
what is the sensory pathway responsible for carrying pain and temperature information from the skin to the thalamus and primary sensory cortex
the spinothalamic tract
where does the spinothalamic tract decussate
2nd order neurone crosses to contralateral spinal cord
are the neurones that carry pain signals to the brain afferent or efferent
afferent sensory neurones
what type of primary afferent fibres tend to carry the sensory information to the spinal cord and why
Alpha-delta fibres
they are myelinated therefore fast conduction
what type of primary afferent fibre tends to carry secondary pain information and why
C fibres
slower conduction as unmyelinated
