Analgesic agents

Question 1

what is the max safe dose of different local anaesthetic agents?

Answer 1

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

Question 2

what is the trade name for bupivacaine?

Answer 2

marcaine

Question 3

what is the trade name for levobupivacaine?

Answer 3

chirocaine

Question 4

how do you calculate amount of local if mls and % is given?

Answer 4

10mg x ml - dose if 1% given
then divide e.g. by 2 if 0.5%

Question 5

what is the general structure of a local anaesthetic agent?

Answer 5

hydrophillic tertiary amine
lipophilic aromatic ring
joined by ester or amide link - determines group

Question 6

which are more stable amides or esters?

Answer 6

amides - ester link is more unstable

Question 7

which fibres are most/ least affected by local?

Answer 7

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

Question 8

how are local anaesthetics metabolised?

Answer 8

esters - plasma esterases (cocaine also liver metabolism)
amides - liver metabolism

Question 9

LAST can result in cardiac arrhythmias. how does this respond to treatment?

Answer 9

refractory to traditional treatment.

Question 10

what is the dosing for intralipid LAST regime

Answer 10

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

Question 11

what step of the WHO ladder does tramadol belong to?

Answer 11

2nd step

Question 12

what is the dose of paracetamol in neonates?

Answer 12

10mg/kg QDS
max oral 60mg/kg/day
max IV 30mg/kg/day

Question 13

what is the dose of paracetamol in children or <50kg

Answer 13

15mg/kg
max oral 75mg/kg/day
max IV 60mg/kg/day

max 4g/day

Question 14

how do 5HT3 inhibitors interact with paracetamol?

Answer 14

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

Question 15

what are the indications for aspirin?

Answer 15

pain
inflammation
MI - primary and secondary prevention
DVT prophylaxis
pre-eclampsia
TIA / ischaemic strokes

Question 16

what does aspirin do to ventilaiton?

Answer 16

uncouples oxidative phos
so need more O2
hence increases ventilation
only significant in overdose

Question 17

what does aspirin do to blood sugar?

Answer 17

reduced BMs at low dose
increased BMs at high dose

Question 18

which overdose is raising urinary pH useful in?

Answer 18

aspirin - ion trapping in urine

Question 19

what factors increase risk of paracetamol toxicity in overdose?

Answer 19

age
malnutrition - less glutathione
liver disease
smoking

Question 20

which COX enzyme when inhibited gives beneficial effects vs side effects?

Answer 20

COX 1 - found in all cells inc stomach and kidney - side effects

cox 2 - found in inflammatory cells - responsible for beneficial effects when inhibited

Question 21

what is a major side effect of the COX 2 specific inhibitors

Answer 21

better side effect profile e.g. GI bleeds etc
HOWEVER - thrombotic cardiac events

Question 22

which of the COX enzymes is inducible?

Answer 22

cox 2

Question 23

are NSAIDS acids or bases?

Answer 23

weak acids

Question 24

where are NSAIDs absorbed from GIT?

Answer 24

in stomach, low pH - unionised
in duodenum less unionised however larger S.A

overall duodenum contributes to most absorption

Question 25

what is the first pass metabolism and protein binding like for NSAIDs?

Answer 25

limited 1st pass metabolism highly protein bound

Question 26

can NSAIDs be used in those undergoing neuroaxial anaesthesia?

Answer 26

yes - platelet inhibition not as significant enough to cause bleeding/ haematoma

Question 27

can nsaids be used in pregnancy?

Answer 27

No - risk of closure of ductus arteriosus

Question 28

why do nsaids cause bronchospasm

Answer 28

inhibtion of COX means that arachidonic acid favours lipo-oxygenase enzyme which makes leukotrienes

Question 29

can NSAIDs be used safetly in paeds

Answer 29

not completely - risk of reyes

Question 30

what are the DDIs of NSAIDs?

Answer 30

increase warfarin - plasma protein binding increase lithium

Question 31

what precursor does B-endorphin come from?

Answer 31

B-endorphin and ACTH are both derived from the same precursor, pro-opiomelanocortin (POMC)

Question 32

what is the main receptor of enkephalins and dorphins?

Answer 32

enkelphalins = mu and delta dynorphins = kappa

Question 33

what endogenous opioid is involved in appetite and circadian rhythm?

Answer 33

dynorphins

Question 34

what type of receptors are opioid receptors and what does activation lead to?

Answer 34

Gi K+ channel activation and hyperpolarisation closure of VG Ca channels hence reduced conductance and NT release

Question 35

which receptors does naloxone antagonise?

Answer 35

mu, delta , kappa

Question 36

give examples of opiates

Answer 36

Morphine, Codeine and Thebaine are examples of opiates - natural everything else and above = opioids

Question 37

how does pentazocine act at opioid receptors

Answer 37

Pentazocine is an example of an agonist/antagonist which antagonises the action of morphine at mu receptors

Question 38

what hormonal side effects do opiates have?

Answer 38

reduce ACTH, LH, FH , prolactin increase ADH

Question 39

do all opioid side effects occur via opioid receptors?

Answer 39

Pruritis is by histamine release from mast cells

Question 40

what is the typical duration of a bolus of morphine?

Answer 40

2-3 hours

Question 41

what is the principle metabolite of morphine?

Answer 41

morphine 3 glucuronide (M6G - is the other but also active)

Question 42

how much more potent is diamorphine than morphine?

Answer 42

x2

Question 43

which is the most rapidly acting opioid?

Answer 43

alfentanil

Question 44

how does potency of pethidine compare to morphine?

Answer 44

1/10th the potency of morphine

Question 45

what metabolises remifentanil?

Answer 45

non specific tissue esterases

Question 46

which of the opioids are Phenylpiperidines vs morphinans

Answer 46

morphinans - oxycodone, diamorphine and morphine phenylpiperidines - fentanyl, pethidine, alfentanil esters - remifentanil

Question 47

In equi-analgesic doses all opioids cause serious side-effects to a similar degree - true or false

Answer 47

TRUE

Question 48

are opioids sterioisomers?

Answer 48

yes - their enantiomers do not have activity at opioid receptor

Question 49

which opioid receptor is responsible for major side effects?

Answer 49

u

Question 50

how does tramadol action differ from traditional opioids?

Answer 50

u agonist but also 5HT3 and NA reuptake inhibitor

Question 51

what is the general oral bioavailability of most opioids?

Answer 51

low

Question 52

what is the elimination half life of morphine? and fentanyl?

Answer 52

3 hours - morphine 3-4hrs - fentanyl

Question 53

do fentanyl and afentanil have active metabolites?

Answer 53

no

Question 54

what particular opioid side effect does tramadol avoid/ reduce?

Answer 54

respiratory depression

Question 55

what PCA should be used in renal failure?

Answer 55

fentanyl - less risk of build up of active metabolities

Question 56

what is codeine metabolised to?

Answer 56

mostly codeine 6 glucuronide - 80% 10% to morphine

Question 57

which has a higher oral bioavailability out of codeine, dihydrocodeine and morphine ?

Answer 57

codeine

Question 58

how does dihydrocodeine compare to morphine and codeine?

Answer 58

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.

Question 59

what are the routes of administration of buprenorphine?

Answer 59

transdermal sublinguial / buccal IV

Question 60

how does buprenorphine interact with MOP and KOP?

Answer 60

MOP - partial agonist, high affinity but lower efficacy than full agonist KOP - antagonist

Question 61

what are the side effects of naloxone?

Answer 61

Naloxone can cause sweating, nausea, restlessness, trembling, vomiting, flushing and headache. can increase sympathetic tone Pulmonary oedema Seizure Arrthymias

Question 62

what is the use of naltrexone?

Answer 62

opioid and alcohol dependence not opioid OD it is a competitve MOP antagonist

Question 63

how do you manage opioid dependance for surgery?

Answer 63

stop any antagonists e.g. naltrexone / buprenorphine may need more opioids continue after

Question 64

which has a shorter half life naloxone or morphine?

Answer 64

Naloxone hence need multiple doses of naloxone or infusion repeated up to max of 10mg

Question 65

which opioids are available as transdermal patch

Answer 65

Buprenorphine Fentanyl

Question 66

What does asthma do to the compliance of the lung?

Answer 66

Increases compliance (unknown reason)

Question 67

What can be given instead of NAC in paracetamol OD?

Answer 67

Methionine - replenishes glutathione

Question 68

How does aspirin affect urate secretion?

Answer 68

High doses promotes excretion - good for gout Low doses does opposite

Question 69

What actions does paracetamol have on receptors

Answer 69

Cox3 inhibition Increases serotoninergic pathways (may be inhibited by ondansetron) Cannabinoid pathways

Question 70

Name 2 cox 2 specific inhibitors

Answer 70

Celecoxib Paracoxib

Question 71

What drugs are meloxicam and piroxicam?

Answer 71

NSAIDs

Question 72

When is naltrexone contraindicated ?

Answer 72

Liver disease

Question 73

What action does baclofen have

Answer 73

GABA B agonist

Question 74

Drugs metabolised by esterases

Answer 74

LA esters Analgesics - aspirin , diamorphine, remifentanil Succinylcholine and mivacurium Heart - esmolol, atropine , enalapril , dabigatran