Pharmacology of GORD

Question 1

give 3 NSAIDs

Answer 1

ibuprofen, naproxen, diclonefac

Question 2

describe the primary mechanism of action for NSAIDs

Answer 2

inhibits cyclo-oxygenase, this is the rate limiting step for production of all prostanoids from arachidonic acid, thought that most wanted effects come from inhibition of COX2 whilst unwanted effects are from COX1 inhibition

Question 3

prostanoids includes

Answer 3

prostaglandins and thromboxanes

Question 4

what is the drug target for NSAIDs

Answer 4

cyclo oxygenase enzyme

Question 5

what are common unwanted effects of NSAIDs

Answer 5

gastric irritation, ulceration and in extreme cases perforation, also reduced creatinine and possible nephritis, bronchoconstriction in susceptible individuals, skin rashes, other allergies, dizziness, tinnitus

Question 6

in which patients is NSAIDs constricted for and why

Answer 6

asthma bc of the bronchoconstrictive effects

Question 7

what are the adverse cardiovascular effects of NSAIDs

Answer 7

hypertension, stroke, MI may occur following prolonged use or in patients with pre-existing CV risk

Question 8

prolonged analgesic abuse of NSAIDs over years is associated with what

Answer 8

chronic renal failure

Question 9

what has aspirin use been linked with

Answer 9

a rare but serious post viral encephalitis (Reye’s syndrome) in children

Question 10

what are the main uses for NSAIDs

Answer 10

analgesics (musculoskeletal pain, headache, dysmenorrhoea), antipyretics, anti inflammatories for chronic control of inflammatory disease

Question 11

what else is aspirin used for

Answer 11

anti aggregatory agent to inhibit platelet aggregation in patient at risk of stroke or MI

Question 12

what chronic inflammatory diseases are NSAIDs used to control

Answer 12

rheumatoid arthritis, OA)

Question 13

give 2 Proton pump inhibitors

Answer 13

omeprazole, lansoprazole

Question 14

what is the primary mechanism of action of PPIs

Answer 14

irreversible inhibitors of H+/K+ ATPase in gastric parietal cells, they are weak bases so accumulate in acid environment of canaliculi or parietal cells which concentrates action and prolongs it too

Question 15

by how much is omeprasole’s action prolonged by

Answer 15

its plasma half life is 1h but single daily dose affects acid secretion for 2-3 days

Question 16

by how much do PPIs inhibit basal and stimulated gastric acid secretion

Answer 16

by over 90%

Question 17

what is the drug target for PPIs

Answer 17

H+/K+ ATPase (proton pump)

Question 18

what are side effects of PPIs

Answer 18

headache, diarrhoea, bloating, abdominal pain, rashes
can also mask gastric cancer symptoms

Question 19

what else does omeprazole do

Answer 19

inhibits cytochrome P2C19 and has been reported to reduce activity of eg clopidogrel when monitoring platelet function

Question 20

are PPIs pro drugs if so how are they metabolised

Answer 20

yes, at low pH converted into 2 reactive species which react with the sulphydryl groups in H+/K+ ATPase

Question 21

how are PPIs administered

Answer 21

orally but bc the degrade rapidly at low pH they are in capsules containing enteric coated granules

Question 22

what is ranitidine

Answer 22

H2 histamine receptor antagonist

Question 23

what is the primary mechanism of action of ranitidine

Answer 23

competitive antagonist of H2 receptors, so inhibit stimulatory action of histamine released from enterochromaffin like (ECL) cells on gastric parietal cells

Question 24

by how much do H2 receptor antagonists reduce gastric secretion

Answer 24

approx 60%

Question 25

what is the drug target for ranitidine

Answer 25

H2 receptor antagonist

Question 26

what are the side effects of H2 receptor antagonists

Answer 26

incidence is low, diarrhoea, dizziness, muscle pains, transient rashes

Question 27

what is cimetidine and what does it do

Answer 27

is a H2 receptor antagonist, inhibits cytochrome P450 and slows metabolism and potentiates the effect of a range of drugs including oral anticoagulants and tricyclic antidepressants

Question 28

how does the dosing for ranitidine work

Answer 28

plasma half life is 2-3h so taken twice daily

Question 29

what does it mean by ranitidine undergoes 1st pass metabolism

Answer 29

undergoes metabolism at specific location and decreases active drug's conc upon reaching systemic circulation, for ranitidine there is 50% bioavailability

Question 30

what is paracetamol also known as

Answer 30

acetaminophen

Question 31

what is the primary mechanism of action of paracetamol

Answer 31

not totally clear peripherally, may inhibit peroxidase enzyme activation of descending serotonergic pathways possible via 5HT3 receptor activation inhibits reuptake of endogenous endocannabinoids

Question 32

what does the peroxidase enzyme do

Answer 32

involved in conversion of arachidonic acid to prostaglandins

Question 33

how can the ability of paracetamol to inhibit peroxidase be blocked

Answer 33

if excessive levels of peroxide build up as is commonly seen in inflammation

Question 34

what would inhibition of the reuptake of endogenous endocannabinoids' effect be

Answer 34

this would increase activation of cannabinoid receptors, which may contribute to activation of descending serotonergic pathways

Question 35

what are the drug targets for paracetamol

Answer 35

5HT3 receptors, cannabinoid reuptake proteins, peroxidase

Question 36

what are side effects of paracetamol

Answer 36

relatively safe

Question 37

what happens if u overdose on paracetamol

Answer 37

liver damage (less frequently renal damage too) nausea vomiting, early features of poisoning (settles in 24h) onset of right subcostal pain after 24h indicates hepatic necrosis

Question 38

paracetamol is taken for what

Answer 38

analgesia and as an anti pyretic, does not possess anti inflammatory activity

Question 39

how does stopping production of prostaglandins through COS by NSAIDs stop pain

Answer 39

prostaglandins sensitise peripheral nociceptors mediators (bradykinin and histamine) which causes pain also indirectly prostaglandins mediate inflammation and so NSAIDs reduce this and thus pain

Question 40

how do NSAIDs cause gastric side effects

Answer 40

by blocking COX1 on gastric mucosal cells, this inhibits prostaglandin production and so inhibits prostaglandin mediated protection of gastric mucosa

Question 41

how do prostaglandins in gastric mucosal cells protect mucosa from acid

Answer 41

increase bicarbonate release, mucus production and blood flow

Question 42

what is the issue of taking both topical diclonefac gel and naproxen

Answer 42

bc diclonefac despite being tpocal can have systemic effects, they are both NSAIDs

Question 43

to manage adverse GI effects what should u prescribe if u want to give NSAIDs to someone with OA or RA or who is elderly

Answer 43

co prescribe PPI with NSAID

Question 44

what do you give to someone with low back pain, axial spondylarthritis, psoriatic arthritis and other peripheral spondylarthritides when u want to give NSAIDs

Answer 44

consider gastroprotection when prescribing NSAID

Question 45

what do u prescribe for those as high, moderate and mild risk of GI adverse vents when giving NSAIDs

Answer 45

for high - prescribe COX2 selective NSAID and PPI for moderate - COX2 inhibitor alone, or NSAID plus PPI for mild - non selective NSAID

Question 46

if u have osteoporosis why might not prescribe a PPI

Answer 46

PPIs known to increase risk of fracture, which is more likely if u have osteoporosis

Question 47

what is the mechanism behind PPIs increasing fracture risk

Answer 47

unclear but thought to be that calcium salt absorption is pH dependent so change in pH induced by PPIs might decrease this and so less calcium is available for bone