GORD/Peptic Ulcer Pharmacology

Question 1

what is the MOA for NSAIDs?

Answer 1

inhibit enzyme cyclo-oxygenase (which generates prostaglandins and thromboxanes)
exibits analgesic effects by reduced prostaglandin effects so less sensitisation to pain
also anti inflammatory via reduced prostaglandin effects

Question 2

what is the drug target for NSAIDs?

Answer 2

cyclo-oxygenase enzyme (COX-1 &2)

COX-1 gives unwanted effects while COX-2 gives the analgesic effect

Question 3

what are the main side effects for NSAIDs?

Answer 3

gastric irritation, ulceration, bleeding, perforation
REDUCED CREATININE CLEARANCE, nephritis,
bronchoconstriction
skin rashes,
dizziness,
tinnitus

Question 4

What are some NSAIDs?

Answer 4

Ibruprofen
Naproxen
Diclofenac

Question 5

what are the risks of long term NSAID use?

Answer 5

CV effects - stroke, MI, hypertension

chronic renal failure/CKD

Question 6

what is the MOA for proton pump inhibitors?

Answer 6

irreversible inhibitor of H+/k+ATP pump in gastric parietal cells
therefore inhibits basal and stimulated gastric acid secretion by over 90%

Question 7

What are some PPIs?

Answer 7

Omeprazole
Lansoprazole

Question 8

what is the drug target for PPIs?

Answer 8

H+/K+ ATP pump

Question 9

what are the main side effects of PPIs?

Answer 9

headache, diarrhoea, bloating, abdominal pain, rashes

may mask gastric cancer

Question 10

what is the MOA for H2 receptor antagonists?

Answer 10

competitive antagonists of H2 histamine receptors
inhibit stimulatory action of histamine release from enterochromaffin-like cells on gastric parietal cells
inhibits gastric acid secretin by ~60%

Question 11

what is the drug target for H2 receptors antagonists?

Answer 11

histamine H2 receptor on gastric parietal cells

stops histamine action after its release from enterochromaffin like cells

Question 12

what are the main side effects of histamine H2 receptor antagonists?

Answer 12

fairly uncommon
diarrhoea, 
dizziness, 
muscle pains, 
transient rashes

Question 13

give examples of H2 receptor antagonists?

Answer 13

cimetidine, rantidine

Question 14

what is an additional side effect of cimetidine (an H2 receptor antagonist)?

Answer 14

inhibits cytochrome P450 may retard metabolism and effect drugs e.g anticoagulants, TCAs

Question 15

what is the MOA of paracetamol?

Answer 15

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 16

what is the drug target for paracetamol?

Answer 16

not yet defined

Question 17

what are the main side effects of paracetamol?

Answer 17

very few effects

in overdose, severe hepatotoxicity

Question 18

how should the adverse GI effects for NSAIDs be avoided?

Answer 18

if any upper abdominal discomfort arises, stop any oral or topical use

Question 19

how do NSAIDs cause GI side effects?

Answer 19

the role of COX-1 includes protection of the stomach lining. this is achieved by increasing bicarbonate release, mucus production and blood flow in gastric mucosa
reducing the stomachs protection may cause discomfort and irritation, ulceration, bleeding, perforation

Question 20

why should those with osteoporosis not be prescribed PPIs and instead use H2 blockers?

Answer 20

increased risk of osteoporosis related fractures
potentially due to altering pH which calcium absorbance is dependent on normally, decreasing amount of calcium available for bone

Question 21

first management step of GORD

Answer 21

test for h.pylori first

Question 22

first line for h.pylori positive

Answer 22

PPI and clarithromycin + amoxicillin (triple therapy)

Question 23

first line for h. pylori negative

Answer 23

address risk factors e.g NSAIDs

if cant be stopped, consider misoprostol or selective COX2 inhibitor

Question 24

first line for GORD with no reversible cause long term

Answer 24

PPI

Question 25

2nd line for no reversible cause long term

Answer 25

H2 receptor antagonist

Question 26

what condition are NSAIDs contraindicated for?

Answer 26

asthma