Analgesic agents Flashcards
what is the WHO ladder for analgesia?
3 step ladder to guide pain management
step 1 - paracetamol, ibuprofen
step 2 - weak opioids, codeine, tramadol
step 3 - strong opioids, morphine, fentanyl
adjuncts can be used along the way - steroids
what are the limitations of the WHO pain ladder?
doesnt account for type of injury e.g. chronic pain problem works for but if someone comes in with broken leg likely to need to start at step 3
doesnt account for neuropathic pain, ketamine or magnesium
Give a hollistic approach to how pain can be managed…
pain is complex can be managed via non pharm and pharmacological approaches.
non pharm - CBT, accupunture
pharm - either direct analgesics or other e.g. PPI or antidepressants
surgical - steroid injections, coeliac plexus block
how does management of visceral pain compare to neuropathic..
visceral - poorly localised, dull pain, potentially referred.
Opiates work well here. Or can consider the cause e.g. buscopan.
neuropathic - opioids dont work so well here.
gabapentin, pregabalin and amitryptilline are used.
capsascin cream - down reg VR1 receptors (substance P). baclofen for muscle spasms
what is the importance of perioperative analgesia?
Better patient experience
Prevention of other issues - early mobilisations, deeper breathing, reduced risk of pneumonias, less N&V, better nutrition and wound healing.
less stress response - risk of MI
what is meant by multimodel analgesia?
targetting pain from different receptors / modes of action
e.g. opioids, regional anaesthesia, paracetamol, ketamine.
means less of one drug has to be used so better side effect profile. opiate sparring
why might pre-emptive analgesia be useful?
better patient experience
less likely to develop chronic pain
easier to stop pain before it develops
which analgesic agents can work topically?
ibuprofen gel
fentanyl and buprenorphine patches - lipid soluble
local anaesthetic creams - EMLA or Ametop
capsaicin cream - initially burning sensation then down reg of VR1 receptors
which neurotransmitters affect descending pain pathways?
opioids - u receptor on SG
ketamine - NMDA receptor at SG
NA/5HT3 e.g. SSRIs and SNRIs , tramadol
reduces noradreanaline - clonidine
what atypical NSAIDs do you know?
paracetamol, aspirin
Tell me about the pathogenesis of paracetamol overdose
paracetamol can be metabolised by phase 1 and phase 2 metabolism within the liver.
In phase 1 - NAPQI is produced which is a toxic metabolite which is quickly conjugated with glutathione.
In phase 2 - paracetamol is glucuronidated - under normal conditions most is metabolised this way.
In OD - phase 2 becomes saturated and phase 1 metabolism increases, meaning more NAPQI produced. Glutathione stores also deplete and hence NAPQI can have toxic effects…
it causes centrolobular necrosis and can lead to fulminant hepatitis.
what factors contribute to depletion of glutathione and put patients at risk of paracetamol toxicity?
malnutrition - low BMI, starvation, malabsorption
genetic polymorphism
extremes of ages
At what level does paracetamol start to cause hepatic injury?
more than 150mg/kg
how does paracetamol OD present
N&V
RUQ pain
dearranged LFTs
after 72 hours - fulminant hepatitis and multiorgan failure
how is paracetamol overdose managed?
A to E, blood inc toxicology
accurate history
within 1 hour - activated charcoal
after than give N - acetylcysteine if - >150mg/kg, staggered overdose, acute liver injury, RUQ and jaundice with signs of liver failure.
otherwise take paracetamol level and use nonagram to decide to give NAC.
what is the dose for N-acetylcysteine?
150mg/kg in 1st hour
50mg /kg over 4 hours
100mg/kg over 16 hours
however now SNAP regime is used - 2 bags
100mg/kg in first 2 hours
200mg/kg in next 10 hours
what is the paracetamol nonagram?
guides need for NAC given levels of paracetamol post insult
not accurate under 4 hours or after 24hrs
no accurate if there is a staggeted overdose
how does N acetylcysteine work?
stimulates glutathione production
binds NAPQI and promotes its conjugation to non toxic products
reduces NAPQI back to paracetamol
any alternatives to NAC?
methionine
what are the ADRs of NAC?
rash, angioedema, flushing , N&V
can result in bronchospasm and low BP
SNAP regime has less incidence of this than classic 3 bag regime
how can the NSAIDs be classified?
Typical and atypical
Selective and non selective COX inhibitors
Typical:
* selective COX2 inhibitors = celecoxib and parecoxib
* non-selective = ibuprofen, ketorolac
atyptical
* aspirin - irreversible COX2 inhibitor
* paracetamol - Cox3 inhibitor
outline the pathway for prostaglandin production and how NSAIDs work..
tell me about COX enzymes
Cycloxygenase enzymes are a group of enzymes responsible for production of prostaglandins
different isoforms exist
COX 1 - found in most cells - particularly GIT, kidneys and platelets. responsible for GI protection, renal blood flow regulation and thromboxane synthesis in platelets
COX 2 - found in immune cells - responsible for prostaglandin production involved in pain and inflammation.
COX 3 - only in CNS - varient of COX 1, pyrexia and interpretation of pain in the brain.
why do NSAIDs exacerbate asthma?
block COX enzymes, build up of arachidonic acid which promotes leukotriene production via lipooxygenase
what role do prostaglandins have in the body
gastric protection - increase blood flow and mucus production to protect epithelium from acid
vasodilation - regulation of blood flow e.g. in kidneys
platelet aggregation - thromboxone and hence homeostasis
uterine contraction in maternity
what is reyes syndrome?
a rare life threatening condition associated with NSAIDs in children.
particularly aspirin
therefore aspirin contraindicated in under 16yrs unless kawasaki disease or juvenile arthritis
results in encephalopathy, cerebral oedema, mitochondrial failure, hepatic failure.
describe the metabolic derrangements seen in aspirin overdose..
mixed respiratory alkalosis + metabolic acidosis
aspirin stimulates resp centre - hyperventilation - resp alkalosis - drives HCO3 excretion which can worsen the acidosis…
also causes uncoupling of oxidative phosphorylation - metabolic acidosis
the acidosis results in increase in unionised form which means more can cross BBB. therefore better to be alkalotic as less toxic. hence sodium bicarb often given in overdose
what is role of sodium bicarb in aspirin OD?
alkalinsation of urine and blood
urine - ion trapping, more aspirin excreted
plasma - ionised form cant cross BBB and have toxic effects.
can also achieve this through hyperventilation if mechanically ventialtion
what are the contraindications to NSAIDs use?
allergy - anaphylaxis or other
GI ulceration / bleed
renal impairment
bleeding risk - caution if on warfarin
under 16yrs
caution in critically ill - AKI and stress ulcers.
Asthma - relative - 10% of asthmatics have an issue
pregnancy - aspirin can be used but mostly avoided due to premature duct closure.
avoid in CKD, HF
what are the indications for NSAIDs use?
pain and inflammation
pyrexia
indomethicin in neonates to help close PDA
what are the pharmacodynamics of NSAIDs..
respiratory
- bronchospasm
- hyperventilation
cardiovascular
* risk of MI - esp COX2 specific
GI:
* ulceration and bleeding
renal
* AKI risk / reduced blood flow
haem
* bleeding risk
neuro
* reyes
how are the NSAIDs classified by their relative effect on GI bleeding risk?
high risk - ketorolac
medium - naproxen, diclofenac
low risk - ibuprofen
COX 2 selective - even lower
what is the benefit of parecoxib / celexocib and risks?
selective for COX2 so target inflammatory effects of prostaglandins more
hence less GI ulceration risk
however found to be associated with thrombosis and MI
do you know any DDIs of NSAIDs…
highly protein bound and therefore displacement of others e.g. warfarin and phenytoin - bleeding risk
SSRIs - risk of bleeding increased,
ACEi - risk of AKI increased.
describe in general the pharmacokinetics of NSAIDs..
A: Oral, IV, gel, PR.
weak organic acids - at stomach pH unionised so can be absorbed, but mostly duodenem due to high S.A
mostly high BO. some 1st pass metabolism
D: highly PB - albumin, low Vd
M + E : hepatic and renal
are NSAIDS contraindicated in neuroaxial blocks?
no
what is the difference between an opiate and opiod?
opiate is naturally ocurring opioid e.g. morphine, codeine
opioids are any molecule that can bind and act on opioid receptors - diamorphine, fentanyl, remifentanil, oxycodone etc - these include synthetic opiouds too.
what are endogenous opioids?
peptides produced in the body and act as neurotransmitters / neuromodulators at the opioid receptors.
mostly found in PAG, hypothalamus, substantia gelatinosa
classed into 3 groups
endorphins - analgesia and euphoria - u and d receptors
enkephalins - analgesia - d and u
dynorphins - kappa receptor - analgesia, appeptite and circadian rhythms
describe the mechanism of an opioid receptor..
GPCR
Gi
found pre synaptically
results in less cAMP, PKA
hyperpolarisation via K+ efflux
reduced Ca via VG Ca Channels.
overall reduced transmission of pain signals
what opioid receptors do you know
4 classes
mu, delta, kappa and nociceptin opioid receptor. also known as MOP, DOP, KOP and NOP.
various subtypes of each
found in PAG, NTS, thalamus, cortex, spinal cord, peripheral nerve terminals and some internal organs,
MOP, DOP And KOP are classical receptors and anatagonised by naloxone
NOP is non classical and not affected by naloxone
what are the specific roles of MOP, KOP, DOP and NOP.
MOP - found in brain, spinal cord and GI plexus - analgesia, euphoria, resp dep, constipation, spasm of spinchter of oddi, N&V , bradycardia.
KOP - brain and spinal cord- analgesia and euphoria, increases ADH. also resp dep
DOP - brain only - analgesia
NOP - brain and spinal - anxiolysis, learning
endogenous opioids receptor ligands…
MOP - B endorphin
KOP - Dynorphin A
DOP - enkephalins
NOP - nociceptin
what are the indications for opioid use?
pain - particularly visceral pain
EoL - breathlessness, anxiety and pain
antitussive
antidiarrhoea
remi - TIVA adjunct to propofol
which opioid is better in somoen with PONV?
alfentanil - wears off quickly so less likely to have post op effects
oxycodone more favourable side effect profile than morphine.
how do PCAs work?
patient controlled analgesia
button to press by patient that delivers a bolus 1-2mg of morphine, 5min lock out time. may also have background infusion running
helps to match analgesia delviery with need and reduce delays for better outcomes.
needs close observation - obs, pain score, record of total dose and needs to be seen by pain team once a day
what is tolerance and dependance?
tolerance - repeated exposure to a drug results in reduced response compared to previously. could be due to downregulation of receptors or uncoupling of intracellular pathways. larger dose needed for same effect
dependance - physical symptoms of withdrawal in absence of drug. person has become dependant on the drug - may be psychological or physiological
what are the effects of opioid withdrawal?
pain
anxiety
feeling cold
sweating
discomfort - abdo cramps
how is an opioid dependant person managed perioperatively?
awareness of need for extra opioids
can use adjuncts e.g. ketamine, paracetamol, regional techniques to reduce the need.
continue methadone programme
what is methadone?
synthetic opiod used for addiction of opioids
full agonist at u receptor and also NMDA antagonist
longer half life than morphine and less sedating
helps relieve withdrawal but has fewer euphoric symptoms so less addictive.
10mg of oral morphine is equivalent to how much oral codeine, dihydrocodeine, tramadol and oxycodone ?
oral codeine / tramadol/ dihydrocodeine = 100mg
oxycodone = 6.6mg
how much morphine equivalnet is a fentanyl 25mcg/hr patch and buprenorphine 5mcg/hr patch?
fent 25mcg/hr = 60mg oral morphine in 24 hours
buprenorphine 5mcg/hr = 12 mg morphine in 24 hours
what is 10mg of morphine equivalent to for IV diamorphine and morphine
IV/SC morphine = 5mg
IV/SC diamorphine = 3.3mg
why does alfentanil have a faster action than a fentanyl
all opioids are weak bases
they ionise below their PKA values.
fentanyl pKA = 8.4
alfentanil PKA = 6.5
at physiological pH therefore using henderson hasselbach equation…
fentanyl is 9:1 ionised / unionised
alfentanil is 1:9 ionised / unionised
therefore much more of alfentanil can cross BBB and exert effects. - much steeper gradient
PLUS
alfentanil is less potent so more of the drug can be used to create a steeper conc gradient.
PLUS
alfentanil is less lipid soluble than fentanyl so has a smaller Vd and therefore doesnt spread into lipid compartments
tell me about dihydrocodeine..
synthetic derivative of codeine
more potent and not as dependant on CYP2D6 so less genetic variability
what is pethidine?
also known as meperidine
synthetic phenyl piperidine
U receptor agonisms but also NA/5HT3 reuptake inhibitor + anticholinergic effects + LA effects
often used in obstetrics
pharmacodynamics
- analgesia
- but also anti-cholinergic effects - dry mouth, urine retention, tachycardia
- risk of serotonin syndrome
- hypertension - risk of hypertensive crisis with MAOi
cautions
- readily crosses the placenta - more lipid sol than morphine
- active metabolite - norpethdine - can cause convulsions (may accumulate in fetus)
tell me about naloxone?
u receptor competitive antagonist (aldo kappa and delta)
used for reversin opioid intoxication
comes in clear colourless solution for IV use
given as 0.1mg - 2mg (titrated to effect)
caution - shorter half life than morphine so may need infusion/ repeat dose
what are the side effects of naloxone?
pulmonary oedema
flushing, headaches
HTN and arrhythmias
pain - withdrawal symptoms
do you know any partial opioid antagonists? what are the benefits of these?
buprenorphine, nalorphine
can help with opioid dependance
compare the elimination of remifentanil and fentanyl?
both very lipid soluble
however differ in metabolism - fentanyl hepatic, remi is unique in that it is metabolised by tissue and plasma esterases
so remi is rapidly hydrolysed and thus effective Vd appears small
very quick offset and context insensitive half life after 10mins
fentanyl can accumulate in tissues due to its large Vd and hence although its clearance is 13 ml/kg/ hr, its half life is 2 hours. It has a context insensitive half time which increases rapidly with length of infusion
how do opioids affect the pain pathway?
peripherally - block peripheral receptors for nerve transmission
ascending pathways - presynaptic - prevent transmission at substantia gelatinosa
descending - in PAG - inhibit release of GABA which results in descending inhibtion
tell me about oxycodone
synthetic opioid
full MOP agonist
like morphine but better side effect profile
food in elderly
and better in renal disease
other than naloxone, do you know any other opioid antagonists?
naltrexone
what other receptors can opioids affect?
mast cells - histamine release
tramadol and pethidine - NA/5HT3 receptor antagonist
pethidine - anticholinergic effects
how is opoid withdrawal managed?
methadone
benzos
supportive care
how does acute opioid intoxication present?
opioids can cause respiratory depression and miosis
often present with low GCS, low RR, pin point pupils
other complication - hypothermia, long lie and rhabdo, risk of I.E, difficult access, malnourished
compare the clearance of opoiods medications and offset of action..
this depends on both their clearance and Vd
clearance of
* morphine = 16ml/kg/hr
* fentanyl =13ml/kg/hr
* alfentanil = 6 ml/kg/hr
so would appear that morphine has quickest offset
however half lifes…
morphine = 170mins
fentanyl = 190mins
alfentanil = 100min
this is because fentanyl is very lipid soluble so althrough clearance is more than double alfentanil, its half life is double.
Vd morphine 3.5, fentanyl 4.0, alfentanil only 0.6 L/kg
t1/2 = (Vd x 0.693) / Clearance
can remifentanil be used in labour?
PCA remi could be used in labour as pain releif - as short term and because rapidly metabolised, doesnt effect fetus
some safety concerns because potent so could cause resp depression - would need monitoring
what other receptors does paracetamol act on ?
COX 3 inhibiton
5HT3 action
what is wooden chest syndrome?
complication of potent opioids, may be seen at induction…
difficult to ventilate
cant be reversed by naloxone but can be by NMBA
tell me about gabapentin..
GABA analgoue but doesnt act on GABA receptors..
works via VG Ca channels blockade in CNS - releasing NT
also increases GABA via GAD
can be used in epilepsy but now more commonly used in pain.
side effects - weight gain, nausea , headaches
tell me about the role of pregabalin in pain?
agent for neuropathic pain
belongs to pro-convulsant drugs
blocks VG Ca channels in CNS reducing transmission of pain. (glutamate and substance P release)
also increases GABA via GAD
what is the role of clonidine in pain?
this acts centrally at pre-synaptic a2 receptor s
blocks release of NA
involved in descending inhibition of pain pathways
can be given IV or neuraxially
other effects include sedation and hypotension.
dexametetomidine - similar but more selective for a2 and more potent.
what analgesic agents do you know..
classed by MoA
NSAIDS - COX inhibition , mostly peripheral
Paracetamol - COX 3 , 5HT3
opioids - U receptor , central and peripheral
neuropathic agents - VG Ca Channels and pain transmission
tramadol and pethidine - mixed actions - opioid, NA/5HT3
KEtamine - NMDA antagonist
N20 - NMDA + opioid
Mg - NMDA + ca antaogonism
clonidine - NA, central
local anaesthetic - peripheral actions.
cannabinoids - cannabinoid receptors
tell me about morphine
naturally occuring opiate
phenathrene derivative
used commonly as analgesic and in palliative care
comes in oral liquid and clear colourless solution for injection.
dose 0.1mg/kg IV. oral 5-20mg 2 hourly.
can also be given intrathecally and epiduraly
modified release also availble.
pharmacodynamics..
full agonist at MOP and KOP
therefore analgesia, euphoria, anxiolysis
other effects considered by system
Resp - depression - low RR, reduces chemoreceptor sensitivity to CO2, chest wall rigidity, supresses laryngeal reflexes, reduces cough. Can result in bronchospasm with histamine release
CVS - bradycardia, hypotension (histamine)
CNS - analgesia, sedation, euphoria, anxiolysis, misosi (via stimulation of edinger westphal nucleus)
GI - N&V , reduces peristalisis - constipation, contraction of spinchter of oddi
endo - reduces ACTH, LH, FSH, increases ADH
Pharmacokinetics…
A: weak base, pKa 8.2. oral absorption from small intestine. BO - 30% .
D: Vd 3.5L/kg, , 30% PB
M: hepatic = morphine 3 glucuronide and M6G. M6G is more active and can accumulate in renal disease
E: renal excretion.
how long does it take for morphine to act?
10mins after IV
30mins after oral
tell me about diamorphine..
diacetylated morphine - synthetic opiate
used for pain, palliative care, breathlessness in pulmonary oedema, and also recreationally.
comes as oral 10mg tablets and also as a powder for IV injection.
given at 10mg IV
more commonly seen intrathecally - 0.1-0.4mg
epidural 3mg
Prodrug which is metabolised to morphine by esterases in plasma and tissues. first to monoacetylmorphine which is a full u agonist and then to morphine.
then acts in same way as morphine but more potent
pharmacokinetics
- A: oral BO 30%, IV. very lipid soluble and pKA 7.6 so more unionised at physiological pH - can rapidly cross BBB.
- D: PB 40%
- M - ester hydrolysis and then hepatic like morphine
- E - renal
why is diamorphine given intrathecally over morphine
more lipid soluble that morphine so acts at target site quicker and shorter lasting.
morphine can linger around - risk of resp depression
tell me about codeine..
naturally occuring opioid , phenathrene derivative
acts as a prodrug which is metabolised into morphine.
used as analgesic agent and antitussive efects and antidiarrhoreal
comes as tablets, oral suspension and can be mixed with paracetamol/ ibuprofen. Not given IV
usually dose of 30-60mg QDS
mechanism + dynamics
1/10th metabolised by liver CYP2D6 to morphine
which then acts at u receptors
therefore similar pharmacodynamics but less potent
IV injection causes a lot of histamine release and hypotension so avoided.
also has stronger anti-tussive effects
pharmacokinetics
A: well absorbed BO 50%
D; v low PB, large Vd
M: 10% to morphine via demethylation , 90% glucuronidation to norcodeine. subject to genetic polymorphism
E: renal
what genetic polymorphisms is codeine subject to?
variation in CYP2D6
some will metabolise codeine very quickly - very sensitive to effects - hypotension, euphoria etc
some will be slower metabolisers or not at all - no analgesic effects
Tell me about fentanyl..
phenylpiperdine derivative
synthetic opioid
used commonly for analgesia in hospitals, as induction agent and sometimes as infusion in ITU. also for chronic pain as transdermal patch
comes as solution for IV injection - 50ug/ml in 2ml ampuoles. also comes as transdermal patch and as lozengers.
At induction normally given 1-2ug/kg e.g. 100ug
acts as a full u agonist
pharmacodynamics
- rapid onset within 2 mins, more potent than morphine and shorter duration
- similar pharmacodynamics
- less histamine release
- because of potency more risk of bradycardia, apnoea and chest wall rigidity
pharmacokinetics
A- small intestine due to pKA 8.4 so ionised in stomach. extensive 1st pass metabolism. very lipid soluble to can cross BBB and can be absorbed across skin (lipid sol and small MW)
D: Vd 4L/kg
M: hepatic - inactive
E: renal
hence safe in renal failure.
tell me about alfentanil..
phenylpiperidine derivative, synthetic opioid
used as fast acting analgesics and induction agent
found in 2ml glass ampuloles as 500ug/ml. Usually 1mg given at induction.
full u agonist
structurally related to fentanyl however lower pKA - 6.5 making it much more unionised at physiological pH so much quicker onset of action (1-2mins) . not as lipid soluble as fentanyl so quicker offset.
A: IV
D: 0.6L/Kg - smaller vd than others , 90% PB
M: liver - inactive metabolites
E: renal, safe in renal failure
tell me about remifentanil..
synthetic opioid
phenylpiperidine derivative
main use in TIVA anaesthesia and for thyroid surgery where no NMBA can be used as it is a strong cough / resp depressant. OR in fibreoptic awake intubation. sedation in ITU for its very short CSHT. can also be used as bolus’s in labour
found as white powder for reconsituting with saline - 50ug/ml solution made.
given as infusion 0.05ug-2ug /kg/min
pure u full agonist
pharmacodynamics
- ultra fast onset and ultra fast acting.
- very potent
- similar to morphine
- profound bradycardia
-very good airway depressant
- risk of hyperalgesia
pharmacokinetics
A: IV , pKA 7.1 - crosses BBB quick because more unionised.
D: very lipid soluble but small Vd due to rapid metabolism
M: ester hydrolsysi - non specific esterases in tissue and plasma - inactive metabolites
t1/2 -5 mins
short CSHT - after 6 mins - no change
E - urinary - carboxylic acids
tell me about tramadol
synthetic opioid
weak mu agonist + 5HT3/NA reuptake inhibitor
effects
* similar to morphine but less resp depression
* less potent
* others
* risk of serotonin syndrome, hypertensive crisis (with SSRIs, MAOI)
* lowers seizure threshold
tell me about buprenorphine…
partial agonist at MOP
antagonist at KOP and DOP
high affinity but low efficacy
therefore in presence of morphine acts as an antagonsit as it competes with morphine for u receptors reducing effects of morphine
however in absence of morphine gives some opioid effects to help with withdrawal
can be given IV, oal , transdermal
what is nalbuphine?
agonist at KOP
antagonist at MOP
tell me about paracetamol..
commonly used analgesic and antipyretic agent. classed as an atypical NSAIDs
comes as oral or IV most commonly
but also suppository.
can be mixed with codeine and other meds e..g caffeine
dose of 1g QDS in adults of normal BMI
in children 15mg/kg
it works via inhibition of COX3 reducing prostaglandin production in brain - hence analgesic and antipyretic effects. also activates descending serotonin pathways which helps with analgesic effects
pharmacodynamics
mostly seen when given IV e.g. hypotension, bradycardia
can cause hepatotoxicity esp in OD
Pharmacokinetics
- A oral / IV - good absorption, BO 80%
- D - small Vd, Pb 10%
- M - hepatic - phase 1 (NAPQI) and phase 2 (glucuronisation and sulphation). under nromal circumstances 90% phase 2
- renal excretion.
tell me about aspirin..
salicylic acid, classed as atypical NSAID, for irreversible COX inhibition.
used for pain, pyrexia, inflammation, antiplatelet effects (primary and secondary prevent of cardiovascular disease)
oral tablet - 75mg, 300mg. also as a suppository
works via non-selective irreversible cox inhibition resulting in reduced prostaglandins and thromboxane. hence reduced pain , inflammation and platelet aggregation.
pharmacodynamics
antiplatelet effects last 7 days due to needing to produce new platelets
- resp - hyperventilation (CNS effect) - resp alkalosis , bronchospasm
- GI - ulceration and bleeding
- renal - risk of AKI
- metabolic - uncouples oxidative phos - metabolic acidosis
- haem - bleeding risk
- CVS - fluid retention - not good for HF
pharmacokinetics
- A: prodrug , good oral absorption from stomach and small intestine. weak acid pKA 3.5, BO 80%
- D: 85% PB, small Vd
- M: hepatic and intestinal esterases metabolism to active form. then liver metabolism. shows 0 order kinetics quickly as liver pathways become saturated
- E: renal excretion
what are the features of aspirin toxicity?
usually mixed resp alk and met acidosis pic with high anion gap
CNS - tinnitus, blurred vision , may lead to seizures
CVS - increased HR, low BP
GI - N&V
resp - hyperventilation, resp alk
glucose derrangements
how is aspirin toxicity managed?
A to E
good HX
if within 1 hr - activated charcoal
avoid intubation unless hypoventilation - as hyperventilation can help create alkalosis to reduce toxic effects
correct electrolyte issues and glucose
sodium bicarb can help to alkalinise blood and urine.
haemodialysis
tell me about ibuprofen..
propionic acid derivative
non selective NSAID
commonly used for pain, inflammation and pyrexia
oral tablets 200mg or oral suspension and as a topical gel
400mg QDS adults, 10mg/kg children
reversible COX inhibitor - reduces prostaglandins dor pain and antipyrexia and anti-inflam.
more favourable side effect profile to other NSAID
do you know any selective COX2 inhibtors , tell me about these…
celecoxib, parecoxib
fewer side effects- GI and renal and bleeding
however MI and thrombotic events
contraindicated in IHD and stroke
tell me about diclofenac..
phenylacetic acid derivative
non -selective reversible COX inhibitor
used as analgesic agent, particularly good PR for renal stones.
50mg/100mg supossitory
oral, suppository, injection and topical gel
more potent but more side effects than ibuprofen
tell me about ketorolac
acetic acid derivative
tablet or IV
30mg IV as slow bolus
more potent and worse bleeding side effects
