GORD/Peptic Ulcer Disease - Core Drugs

Question 1

List drug classes used to treat GORD/PUD

Answer 1

NSAIDs
proton pump inhibitors
Histamine (H2) receptor antagonists
paracetamol

Question 2

list examples of NSAIDs used to treat GORD/PUD

Answer 2

ibuprofen
naproxen
diclofenac

Question 3

primary mechanism of action of NSAIDs

Answer 3

inhibits COX enzyme > slows production of prostaglandins & thromboxanes

Question 4

It is thought that the anti-inflammatory actions, and probably most of the analgesic & antipyretic actions, of the NSAIDs are related to inhibition of?

Answer 4

COX-2

Question 5

It is thought that the unwanted effects of NSAIDs are largely a result of?

Answer 5

inhibition of COX-1

Question 6

drug target of NSAIDs

Answer 6

COX enzyme

Question 7

side effects of NSAIDs

Answer 7

gastric irritation, ulceration and bleeding and, in extreme cases, perforation; reduced creatinine clearance and possible nephritis, Skin rashes & other allergies, dizziness, tinnitus.

adverse CVS effects (hypertension, stroke, MI) may occur following prolonged use or in patients with pre-existing CV risk.

Prolonged analgesic abuse over a period of years is associated with chronic renal failure.

Question 8

Aspirin has been linked with what in children?

Answer 8

rare but serious post-viral encephalitis (Reye’s syndrome)

Question 9

main uses of NSAIDs

Answer 9

analgesics for mild/moderate pain
antipyretics
antiinflammatory
(aspirin only) as an anti-aggregatory

Question 10

NSAIDs are contraindicated for what population and why?

Answer 10

asthma

causes bronchoconstriction

Question 11

list examples of proton pump inhibitors used to treat GORD/PUD

Answer 11

omeprazole

lansoprazole

Question 12

drug target for proton pump inhibitors

Answer 12

H+/K+ ATPase (‘proton pump’)

Question 13

mechanism of action of proton pump inhibitors

Answer 13

irreversible inhibitors of H+/K+ ATPase in gastric parietal cells > are weak bases + accumulate in acid environment of canaliculi > concentrates their actions there and prolongs their duration of action

Question 14

omeprazole plasma half life

Answer 14

1 hour

Question 15

single daily dose of omeprazole affects acid secretion for how long?

Answer 15

2-3 days

Question 16

side effects of proton pump inhibitors

Answer 16

headache, diarrhoea, bloating, abdominal pain & rashes

Question 17

use of proton pump inhibitors can mask the symptoms of what disease?

Answer 17

gastric cancer

Question 18

omeprazole is also an inhibitor of _____ and has been reported to reduce the activity of _____

Answer 18

cytochrome P2C19

clopidogrel

Question 19

how are PPIs administered?

Answer 19

orally but degrade rapidly at low pH so administered as capsules containing enteric-coated granules.

Question 20

PPIs are pro drugs. how are they converted to their active forms?

Answer 20

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

Question 21

list an example of a histamine (H2) receptor antagonist

Answer 21

ranitidine

cimetidine

Question 22

drug target of histamine (H2) receptor antagonist

Answer 22

histamine H2 receptor

Question 23

mechanism of action of histamine receptors antagonist

Answer 23

competitive antagonists (structural analogues of histamine) > inhibit stimulatory action of histamine released from enterochromaffin-like (ECL) cells on the gastric parietal cells

Question 24

list side effects of histamine receptor antagonists

Answer 24

diarrhoea
dizziness
muscle pains
transient rashes

Question 25

cimetidine also inhibits?

Answer 25

cytochrome P450

Question 26

other actions of cimetidine include?

Answer 26

may retard the metabolism and potentiate the effects of a range of drugs incl. oral anticoagulants and TCAs

Question 27

ranitidine plasma half life?

Answer 27

2-3 hours

Question 28

bioavailability of ranitidine

Answer 28

undergoes first pass metabolism | 50% bioavailability

Question 29

drug target of paracetamol

Answer 29

Not yet well defined. COX-3 isoform?

Question 30

mechanism of action of paracetamol is unclear. list examples of current hypotheses

Answer 30

interaction with a COX-3 isoform (inhibition of PG synthesis), cannabinoid receptors or the endogenous opioids. also Interactions at 5HT & adenosine receptors

Question 31

In serious overdose of paracetamol what can occur?

Answer 31

serious hepatotoxicity | occasional allergic skin reaction

Question 32

main uses of paracetamol

Answer 32

analgesic | anti-pyretic activity