pharmacology of analgesia

Question 1

MOA of paracetamol

Answer 1

unclear
activation of descending serotinergic pathways possibly via 5HT3 receptor
mild inhibition of cylcooxygenase
inhibits reuptake of endogenous endocannabinoids increasing activation of cannabinoid receptors

Question 2

drug target paracetamol

Answer 2

poss 5HT3/cannabinoid reuptake proteins/cyclooxygenase

Question 3

paracetamol side effects

Answer 3

safe

hepatic toxicity in overdose, renal damage

Question 4

paracetamol overdose

Answer 4

liver damage, renal damage

nausea and vomiting within 24hrs, right subcostal pain after 24hr indicates hepatic necrosis

Question 5

what does paracetamol do?

Answer 5

anti pyretic
analgesic
NOT antiinflammatory

Question 6

why does paracetamol not have any anti inflammatory effects?

Answer 6

paracetamol inhibits peroxidase activity

peroxides are produced by inflamed tissues, outcompete paracetamol for peroxidase enzyme

Question 7

weak opioids

Answer 7

codeine

tramadol

Question 8

strong opioids

Answer 8

morphine

fentanyl (heroin)

Question 9

MOA opioids (4)

Answer 9

works on nocireceptors via opioid receptor (g protein coupled)
depresses cellular activity by inhibiting adenylate cyclase (reduce ATP-cAMP)
reduces Ca2+ influx so less exocytosis of neurotransmitter
increased K+ efflux, hyperpolarises cell so cant depolarise
inhibits GABA which disinhibits pain signals, activates modulation of pain signal transmission

Question 10

drug target for opioids

Answer 10

opioid receptor on nocireceptors

GABA

Question 11

how does GABA disinhibition work for opioids?

Answer 11

opioids work to inhibit GABA
GABA is responsible for inhibiting the modulation (inhibition) of pain signals from the brain
therefore inhibiting GABA transmission, disinhibits (inhibits its inhibition) modulation of pain signals so that they are reduced and less pain is felt

Question 12

what is the process of feeling pain from finger to brain?

Answer 12

transduction of stimulus from nocireceptor to sensory neurone in spinal cord
synapses to spinothalamic neurone
transmission of pain signal to higher brain structures by spinothalamic neurone
perception of pain signal in brain
modulation of pain signal (inhibits incoming signal to stop feeling painful stimulus) via sensory/spinothalamic neurone
pain goes away

Question 13

side effects of opioids?

Answer 13

nausea and vomiting

constipation

Question 14

how do opioids cause nausea and vomiting side effects?

Answer 14

increase activity in chemoreceptor trigger zone

Question 15

how do opioids cause constipation?

Answer 15

lots of opioid receptors in gastrointestinal tract can reduce gut motility through reduced peristaltic contractions

Question 16

what happens in opioid overdose?

Answer 16

respiratory depression via direct and indirect inhibition of respiratory control centre

Question 17

MOA of co-amoxiclav

Answer 17

amoxicillin - binds to bacterial penicillin binding proteins
prevents transpeptidation for cell wall synthesis
clavulanate - beta lactamase inhibitor, bacterial enzyme which degrades penicillins (reduces resistance to antibiotics by inhibiting this)

Question 18

drug target for co-amoxiclav?

Answer 18

amoxicillin - penicillin binding proteins

clavulanate - beta lactamase

Question 19

side effects of co-amoxiclav?

Answer 19

well tolerated

nausea and diarrhoea possible

Question 20

MOA of lactulose

Answer 20

non-absorbable disaccharide
causes water retention via osmosis as reaches the large intestine undigested
makes stool easier to pass
can be metabolised by colonic bacteria inducing a laxative effect

Question 21

side effects of lactulose?

Answer 21

abdominal pain
diarrhoea
flatulence
nausea

Question 22

how long does it take lactulose to be effective?

Answer 22

2 days to improve constipation

onset within 8-12 hours

Question 23

how to know someone has overdosed on opioids

Answer 23

cardiorespiratory depression
unconscious
cyanosis secondary to resp depresh
pin prick pupils when unconscious