Analgesic agents Flashcards
what is the max safe dose of different local anaesthetic agents?
bupivacaine - 2mg/kg (2.5mg/kg with adrenaline)
levobupivacaine - 2.5mg/kg
lidocaine - 3mg/kg (7mg/kg with adrenaline)
prilocaine - 6mg/kg
ropivacaine - 3-4mg/kg
what is the trade name for bupivacaine?
marcaine
what is the trade name for levobupivacaine?
chirocaine
how do you calculate amount of local if mls and % is given?
10mg x ml - dose if 1% given
then divide e.g. by 2 if 0.5%
what is the general structure of a local anaesthetic agent?
hydrophillic tertiary amine
lipophilic aromatic ring
joined by ester or amide link - determines group
which are more stable amides or esters?
amides - ester link is more unstable
which fibres are most/ least affected by local?
small > big
myelinated > unmyelinated
hence best = B myelinated e.g. sympathetic pre ganglionic
next A delta
Aa and Ag - too big
C - non myelinated, most resistant
how are local anaesthetics metabolised?
esters - plasma esterases (cocaine also liver metabolism)
amides - liver metabolism
LAST can result in cardiac arrhythmias. how does this respond to treatment?
refractory to traditional treatment.
what is the dosing for intralipid LAST regime
1.5ml/kg bolus
15ml/kg/ hr infusion
second bolus - 1.5ml/kg
second infusion- 30ml/kg/hr
3rd bolus can be given
max 12ml/kg
what step of the WHO ladder does tramadol belong to?
2nd step
what is the dose of paracetamol in neonates?
10mg/kg QDS
max oral 60mg/kg/day
max IV 30mg/kg/day
what is the dose of paracetamol in children or <50kg
15mg/kg
max oral 75mg/kg/day
max IV 60mg/kg/day
max 4g/day
how do 5HT3 inhibitors interact with paracetamol?
paracetamol exerts some of its effects through 5HT3 reuptake blocking
Granisetron and Tropisetron have been shown to block the analgesic action of paracetamol. This is not seen with Ondansetron
what are the indications for aspirin?
pain
inflammation
MI - primary and secondary prevention
DVT prophylaxis
pre-eclampsia
TIA / ischaemic strokes
what does aspirin do to ventilaiton?
uncouples oxidative phos
so need more O2
hence increases ventilation
only significant in overdose
what does aspirin do to blood sugar?
reduced BMs at low dose
increased BMs at high dose
which overdose is raising urinary pH useful in?
aspirin - ion trapping in urine
what factors increase risk of paracetamol toxicity in overdose?
age
malnutrition - less glutathione
liver disease
smoking
which COX enzyme when inhibited gives beneficial effects vs side effects?
COX 1 - found in all cells inc stomach and kidney - side effects
cox 2 - found in inflammatory cells - responsible for beneficial effects when inhibited
what is a major side effect of the COX 2 specific inhibitors
better side effect profile e.g. GI bleeds etc
HOWEVER - thrombotic cardiac events
which of the COX enzymes is inducible?
cox 2
are NSAIDS acids or bases?
weak acids
where are NSAIDs absorbed from GIT?
in stomach, low pH - unionised
in duodenum less unionised however larger S.A
overall duodenum contributes to most absorption
what is the first pass metabolism and protein binding like for NSAIDs?
limited 1st pass metabolism
highly protein bound
can NSAIDs be used in those undergoing neuroaxial anaesthesia?
yes - platelet inhibition not as significant enough to cause bleeding/ haematoma
can nsaids be used in pregnancy?
No - risk of closure of ductus arteriosus
why do nsaids cause bronchospasm
inhibtion of COX means that arachidonic acid favours lipo-oxygenase enzyme which makes leukotrienes
can NSAIDs be used safetly in paeds
not completely - risk of reyes
what are the DDIs of NSAIDs?
increase warfarin - plasma protein binding
increase lithium
what precursor does B-endorphin come from?
B-endorphin and ACTH are both derived from the same precursor, pro-opiomelanocortin (POMC)
what is the main receptor of enkephalins and dorphins?
enkelphalins = mu and delta
dynorphins = kappa
what endogenous opioid is involved in appetite and circadian rhythm?
dynorphins
what type of receptors are opioid receptors and what does activation lead to?
Gi
K+ channel activation and hyperpolarisation
closure of VG Ca channels
hence reduced conductance and NT release
which receptors does naloxone antagonise?
mu, delta , kappa
give examples of opiates
Morphine, Codeine and Thebaine are examples of opiates - natural
everything else and above = opioids
how does pentazocine act at opioid receptors
Pentazocine is an example of an agonist/antagonist which antagonises the action of morphine at mu receptors
what hormonal side effects do opiates have?
reduce ACTH, LH, FH , prolactin
increase ADH
do all opioid side effects occur via opioid receptors?
Pruritis is by histamine release from mast cells
what is the typical duration of a bolus of morphine?
2-3 hours
what is the principle metabolite of morphine?
morphine 3 glucuronide
(M6G - is the other but also active)
how much more potent is diamorphine than morphine?
x2
which is the most rapidly acting opioid?
alfentanil
how does potency of pethidine compare to morphine?
1/10th the potency of morphine
what metabolises remifentanil?
non specific tissue esterases
which of the opioids are Phenylpiperidines vs morphinans
morphinans - oxycodone, diamorphine and morphine
phenylpiperidines - fentanyl, pethidine, alfentanil
esters - remifentanil
In equi-analgesic doses all opioids cause serious side-effects to a similar degree - true or false
TRUE
are opioids sterioisomers?
yes - their enantiomers do not have activity at opioid receptor
which opioid receptor is responsible for major side effects?
u
how does tramadol action differ from traditional opioids?
u agonist
but also 5HT3 and NA reuptake inhibitor
what is the general oral bioavailability of most opioids?
low
what is the elimination half life of morphine? and fentanyl?
3 hours - morphine
3-4hrs - fentanyl
do fentanyl and afentanil have active metabolites?
no
what particular opioid side effect does tramadol avoid/ reduce?
respiratory depression
what PCA should be used in renal failure?
fentanyl - less risk of build up of active metabolities
what is codeine metabolised to?
mostly codeine 6 glucuronide - 80%
10% to morphine
which has a higher oral bioavailability out of codeine, dihydrocodeine and morphine ?
codeine
how does dihydrocodeine compare to morphine and codeine?
more potent than codeine
but still a weak opioid like codeine
Dihydrocodeine has a lower bioavailability than codeine, which is why they have similar doses, despite dihydrocodeine being more potent.
what are the routes of administration of buprenorphine?
transdermal
sublinguial / buccal
IV
how does buprenorphine interact with MOP and KOP?
MOP - partial agonist, high affinity but lower efficacy than full agonist
KOP - antagonist
what are the side effects of naloxone?
Naloxone can cause sweating, nausea, restlessness, trembling, vomiting, flushing and headache.
can increase sympathetic tone
Pulmonary oedema
Seizure
Arrthymias
what is the use of naltrexone?
opioid and alcohol dependence
not opioid OD
it is a competitve MOP antagonist
how do you manage opioid dependance for surgery?
stop any antagonists e.g. naltrexone / buprenorphine
may need more opioids
continue after
which has a shorter half life naloxone or morphine?
Naloxone
hence need multiple doses of naloxone or infusion
repeated up to max of 10mg
which opioids are available as transdermal patch
Buprenorphine
Fentanyl
What does asthma do to the compliance of the lung?
Increases compliance (unknown reason)
What can be given instead of NAC in paracetamol OD?
Methionine - replenishes glutathione
How does aspirin affect urate secretion?
High doses promotes excretion - good for gout
Low doses does opposite
What actions does paracetamol have on receptors
Cox3 inhibition
Increases serotoninergic pathways (may be inhibited by ondansetron)
Cannabinoid pathways
Name 2 cox 2 specific inhibitors
Celecoxib
Paracoxib
What drugs are meloxicam and piroxicam?
NSAIDs
When is naltrexone contraindicated ?
Liver disease
What action does baclofen have
GABA B agonist
Drugs metabolised by esterases
LA esters
Analgesics - aspirin , diamorphine, remifentanil
Succinylcholine and mivacurium
Heart - esmolol, atropine , enalapril , dabigatran
