Pharmacology of opioids Flashcards
PAIN PATHWAY
i) what is the 6 step pathway from periph nerve to higher centres?
ii) which spinal tract carries pain? where is it then processed
iii) how governs how much pain is percieved?
iv) which three levels can pain be modulated on? where is most done?
v) what may be given for people with malignant long term pain?
i) periph nerve > DRG > DH > sp cord > brain stem > higher centres
ii) spino thalamic tract > thalamus
iii) number of receptors
iv) local, cord or central level > most is done at central level
v) implantable/inducible pain relief
PAIN PATHOPHYSIOLOGY
i) what are the symptoms of somatic nociceptive pain? name two causes? name two examples
ii) what are the symptoms of visceral nociceptive pain? name two causes? name two examples
iii) what are the symptoms of neuropathic pain? name two causes? name two examples
i) somatic noci > localised, aching, throbbing, gnawing
- caused by activat of noci in skin, musc and bone
- bone mets, tumour invas to soft tissue, muscle spasicity
ii) visc noci > poorly loc, deep, aching, cramping, pressure
- caused by activ of noci from stretching, disten, inflam
- bowel obstrc, panc cancer, liver mets
iii) neuropathic > burning, shooting, electric, often dermatomal
- peripheral or spinal nerve damage can be cause
- tumour or tx damage to nerve plexus, post herp neuralgia, sp cord copress, diabetic neuropathy
ANALGESIA
i) name a drug type that may act at site of injury/decrease pain assoc with inflam reaction?
ii) what drugs may alter nerve conduction?
iii) name two drugs that can mod transmission at the DH
iv) which two types of drug may affect central component/emotional aspects of pain
v) name four adjuvant analgesics - pharma and non pharma
i) NSAIDs
ii) local anaes
iii) opioids and some anti depressants
iv) opioids and anxiolytics
v) adjuvant - drugs used for other things but also help with pain
- pharma = steroids, bisphos, anti dep, anti ep, anti chol, antibiotoics
- non pharma - TENS, acupuncture, massage, heat, psych support
OPIOIDS
i) name three endog opioids
ii) what is an opioid?
iii) where are most opioid receptors found? name three other places?
iv) which endog opioid binds mu, kappa, delta and give an eg of what each binding does
i) beta endorphin, dynorphin, enkephalin
ii) naturally occuring or synthetic with affinity for opioid receptors that can be reversed by naloxone
iii) most found in cell mem of neurons in the CNS
- also found in enteric gut plex, periph sensory afferent nerves, dorsal root cells
- 70% are found pre synaptically
iv) mu > beta endorphin > analgesia, resp dep, euphoria, constip
kappa > dynorphin > analgesia, miosis, diuresis
delta > enkephalin > analgesia, resp dep
MECH OF OPIOID ACTION AT A RECEPTOR LEVEL
i) where do opioid analgesics activate their receptors? what type of receptors are these
ii) what are the two main parts of opioid receptors
iii) which channels are closed and which are open in the pre syn neuron after opioid R activation?
iv) how does activation of opioid receptors affect descending transmission of nociceptive information between sp cord and DH? which pathways are activated?
v) name four other effects of opioids
i) activate Rs in cell mem of nociceptive neurons
- GPCRs
ii) membrane spanning R protein and G protein complex = alpha, beta, gamma
iii) calcium channels are closed and potassium channels are open > hyperpol and reduc in NT (glu, ach, sup P) > pre and post synaptic inhibition
iv) inhibits asc transmission and activates desc pain control circuits from midbrain to DH
v) psychotropic (anxiolytic, sedation, euphoria, hallucinate), resp dep, supress cough reflex, N+V (CTZ), miosis (excite on psym NS)
OTHER EFFECTS OF OPIOIDS
i) how do they cause constipation?
ii) how do they cause histamine release?
iii) which three hormones may be increased? why?
iv) how do they affect heart rate?
v) name three issues with opioid use
i) delayed gastric empty and inhib of peristalsis
ii) opioid receptors on mast cels can cause hist release > rash, pruritis, hypoten and bronchospasm
iii) increase PRL, GH and ADH due to stim of D2 reecptors in hypothalamus
iv) inc symp drive to SA node depress > brady
v) tolerance, physical dependence, addiction, toxicity
PHARMACOKINETICS OF OPIOIDS
i) how are opioids absorbed when delivered orally? how are they metabolised? what is their onset of action? when does action peak?
ii) can opioids be delivered transdermal? why? which opioid?
iii) what must be considered when delivering SC eg IM or IV?
iv) give an admin route that crosses BBB > SA space? which route needs to cross the dura to get to SA space?
i) abs across GI > first pass hepatic metab
- onset in 20-40 mins with peak at 30-60mins
ii) yes as they are lipophilic > fentanyl
iii) 100% bioavail
iv) BBB > SA space directly = intra thecal
BBB > dura > SA = epidural
PHARMACOKINETICS OF OPIOIDS
i) is there high plasma protein binding? which have quicker onset?
ii) which organ primarly metabolises them?
iii) how are they excreted?
i) plas prot binding 30% morphine, 80% fentanyl
ii) liver > water sol products
iii) excreted renally - use fentanyl based drugs more in renal impair
MORPHINE
i) when is it the choice?
ii) which two opioid receptors does it act at? which route of admin is it well abs from?
iii) where is it metab?
iv) how is it excreted?
v) what are the two types of morphine? which is usually preferred and why
i) mod to severe pain
ii) acts at mu and kappa receptors (agonist) > well orally abs
iii) metab in liver
iv) excreted in urine
v) immed release and sustained release
- prefer sustained as it works for 12 hours (rather than 4) but same half life of IR
OXYCODONE
i) when is it used?
ii) where is it metabolised? are its metabolised active or inactive?
iii) what is its oral bioavail? when should caution be taken
i) second line in mod/severe pain
ii) metab in liver > active metabolites
iii) high oral bioaval > take caution in renal failure
FENTANYL PATCHES
i) who are they not suitable for?
ii) how long does depot remain in skin after removal?
iii) how is it metab? how is it excreted?
i) not suitanle for patients with unstable or rapid escalating pain
ii) stays in skin for 24 hrs post removal (forms a reservoir under the skin)
iii) liver metab and high clearance > excreted in urine
ALFENTANIL
i) when is it used?
ii) how potent is it? what is approx half life?
iii) where is it metab? are metabolites active or inactive?
iv) when is it the opioid of choice? how can it be given?
v) in what two situations may clearance be reduced
i) third line used with specialist advice
ii) very potent and short acting - half life is 30 mins
iii) metab by the liver > inactive metabs
iv) opioid of choice when eGFR <30
- can be injected
v) reduced in liver impair and in older patients
SUBCUT SYRINGE PUMPS
i) how does it deliver drugs?
ii) which group of patients is it useful in?
iii) do you need an IV line?
i) delivers drugs through continuous infusion
ii) good in end of life patients > can mix different drugs
- good if patient is being sick etc
iii) no
CHANGING OPIOIDS
i) what is opioid switch?
ii) what is opioid rotation
i) sub one strong opioid for another in attempt to acheive better balance of pain relief and side effects
ii) swtiching to an alt opioid to improve pain or side effects but also changes route of admin
