pharmacology of pain

Question 1

give weak and strong opioids

Answer 1

weak - codeine and tramadol
strong - morphine, fentanyl, heroin

Question 2

what is the primary mechanism of action of opioids

Answer 2

depressant effect on cellular activity, has multiple sites in pain pathways where activation of opioid receptor gives decreased perception or increased tolerance to pain

Question 3

how do opioids have an antitussive effect and what does this mean

Answer 3

anti tussive = suppresses coughs
due to decreased activation of afferent nerves relaying cough stimulus from airways to brain

Question 4

drug target for opioids

Answer 4

opioid receptor

Question 5

side effects of opioids

Answer 5

mild nausea and vomiting (increase in chemoreceptor trigger zone) and constipation (opioid receptor in GIT can reduce gut motility)

Question 6

what happens when u overdose on opioids

Answer 6

respiratory depression (direct and indirect inhibition of respiratory control centre)

Question 7

co amoxiclav mechanism of action

Answer 7

amoxicilin binds to penicilin binding proteins, preventing transpeptidation (cross linking for bacterial cell wall synthesis)
clavulanate inhibits beta lactamase which degrades beta lactam antibiotics and gives resistance

Question 8

drug target for co amoxiclav

Answer 8

amoxicilin = penicillin binding proteins
clavulanate = beta lactamase

Question 9

side effects of co amoxiclav

Answer 9

nausea and diarrhoea

Question 10

hypersensitivity to penicillin leads to what

Answer 10

rash but can lead to anaphylactic reactions

Question 10

is amoxicillin for gram positive or negative

Answer 10

both as it is a broad spectrum

Question 11

lactulose mechanism of action

Answer 11

non absorbable disaccharide, reaches large bowel unchanged, causes water retention via osmosis and an easier to pass stool, can be metabolised by colonic bacteria, colonic metabolism of sugars has additional laxative effect

Question 12

drug target of lactulose

Answer 12

no drug target

Question 13

side effects of lactulose

Answer 13

abdominal pain, diarrhoea, flatulence, nausea

Question 14

how long does lactulose take to work

Answer 14

within 8-12h but make take upto 2 days to improve constipation

Question 15

when is lactulose prescribed

Answer 15

often prior to starting opioid therapy to improve the very common side effect of constipation

Question 16

if diagnosed with gastroenteritis how should u be managed

Answer 16

oral rehydration - diarrhoea and vomiting risks dehydration
analgesia

Question 17

what do u give for mild, mild to moderate and moderate to severe pain

Answer 17

mild - non opioid +/- adjuvant therapy
mild to moderate - weak opioid +/- nonopioid +/- adjuvant therapy
moderate to severe - strong opioid +/- nonopioid +/- adjuvant therapy

Question 18

what does paracetamol 1g PO QDS PRN mean

Answer 18

to be taken 4 times daily (QDS) when required (PRN) by mouth (PO)

Question 19

what are the different steps in the pain pathway

Answer 19

stimulus at skin leads to transduction, this is transmitted upto CNS where there is perception in the brain, then modulation goes from brain down to spine (these consist of inhibitory signals down to the spinal cord to inhibit the incoming stimulus, this allows us to function enough to respond to the pain by reducing its signal through neuronal disinhibition)

Question 20

what is andamide

Answer 20

can be broken down into arachidonic acid by fatty acid amide hydrolase so when NSAIDs and paracetamol inhibit prostaglandin prodction there is a build up arachidonic acid
leads to build up of andamide
it activates descending pain pathways which are the inhibitory ones so andamide gives analgesia

Question 21

what signs can u see in acute appendicitis

Answer 21

worsening pain over 2h, moved to RLQ, tender in right iliac fossa, guarding and rebound tenderness, high WCC count and CRP

Question 22

what do u do for acute appendicitis

Answer 22

surgery - open laparoscopy
hydration - would need to be NBM so IV crystalloids
analgesia
antibiotics

Question 23

why do u give antibiotics in acute appendicitis pre op

Answer 23

obstructed appendix could lead to bacterial overgrowth, plus risk of post-surgical infection

Question 24

what effect does morphine have at the cellular level

Answer 24

morphine is an opioid
binds to the mu receptor on pre synaptic neuron, which is a G protein coupled receptor
this leads to enhancement of K+ efflux out the neuron (hyperpolarisation, so neuron cant fire)
inhibits adenylate cyclase which would do the conversion of ATP to cAMP (less cellular activity)
inhibits Ca2+ influx into the neuron (less exocytosis of NT)

Question 25

what effect does morphine then have on the pain pathways

Answer 25

inhibits the stimulus transduced pain into a signal
also inhibits transmission of pain signal in spinal cord
activates disinhibition in the modulation stage - this is bc GABA switched off descending pathways, so inhibiting GABA switches off the off button leading to activation of descending pathways and disinhibition

Question 26

what is the major route for drug permeation into the brain

Answer 26

via passive diffusion, lipid solubility of the drug is the major determinant of this passive diffusion

Question 27

what is opioid receptor binding dependent on when it comes to chemical structure

Answer 27

a hydroxyl group at position 3 and a tertiary (refers to the 3D arrangement) nitrogen

Question 28

what is the optimal lipid solubility needed for entering brain tissue

Answer 28

1.5 - 2.7

Question 29

refer to image in notion

Question 30

what forces are there between the opioid receptor and the tertiary nitrogen in the opioid

Answer 30

ionic

Question 31

what forces are there between the drug binding sites and the other CH groups in the opioid

Answer 31

Van den Waal’s

Question 32

what forces are there between the drug binding sites and the hydroxyl group in the opioid

Answer 32

hydrogen bond

Question 33

what is naloxone

Answer 33

an opioid receptor antagonist, given IV after opioid overdoses, this is the antagonist whereas morphine was an agonist

Question 34

compare the chemical structure of nalocone and morphine and explain their differing actions

Answer 34

Similarities: both have hydroxyl group at position 3 and both have tertiary nitrogen, so both can bind to receptor

Structural differences: short side chain at tertiary nitrogen allows effect. Long side chain cannot fit in binding site so can’t activate receptor so blocks receptor

Question 35

how do u do the morphine to codeine dose conversion

Answer 35

divide total daily morphine dose by 0.1 to get daily codeine dose in mg

Question 36

why is the dose reduction recommendation of opioids when taking home and why

Answer 36

reduced by 30% to reduce risk of overdose, but may not be necessary in a young man with no other underlying medical conditions

Question 37

what is codeine

Answer 37

a pro drug for morphine

Question 38

what 2 things can codeine be metabolised into

Answer 38

norcodeine (inactive metabolite)
morphine (active)

Question 39

what is responsible for metabolism of codeine

Answer 39

in the liver, cytochrome P450
CYP3A4 responsible for fast metabolism of codeine to norcodeine
CYP2A6 does slow metabolism of codeine to morphine

Question 40

what is the significance of slow and fast metabolism of codeine

Answer 40

fast metabolism into norcodeine and slow into morphine, 90% of oral codeine is inactivated and 10% is activated, therefore making codeine a weak opioid