lecture 5

Question 1

Fundus cells

Answer 1

parietal and non - parietal mucosal epithelial

Question 2

antrum cells

Answer 2

G cells and D cells

Question 3

effect of local anaethetics related to lignocaine when taken orally

Answer 3

reduce gastric acid secretion

Question 4

which antiviral drug slows gastric acid secretion as a side effect

Answer 4

pyridylthioacetamide

Question 5

what caused the anti-secretory activity

Answer 5

rearranged carbon, sulfur and nitrogen bonds

Question 6

what causes steven johnstone syndrome

Answer 6

c=s, so you want to remmove this , which is why scn grouups were investigated

Question 7

why are esters key to a good pro drug

Answer 7

cos they break down when they go through the GIT

Question 8

why cant an ester be of pharmacological importance for a drug

Answer 8

it falls apart too easily so it wont work when it goes down the GIT

Question 9

how do you make a molecule more stable if it contains an ester

Answer 9

replace it with an ester

Question 10

what was the issue with timoprazole

Answer 10

it prevented uptake of iodine by the thydroid => picoprazole

Question 11

how was picoprazole improved

Answer 11

increased pKa of the pyridine ring by placing electron donating groups on it (ch3 and ch3o)

Question 12

NHpka and imidizole pKa

Answer 12

8.7 and 4

Question 13

what does a low pH do when theres lone pairs

Answer 13

anything with lone pairs protonates at a low pH

Question 14

where is omeprazole ionised

Answer 14

low pH from parietal cell ionises it and makes it get trapped here as it then cant diffuse back out when its ionised

Question 15

what is the activve form of omeprazole

Answer 15

sulphenamide

Question 16

why is sulphenamide permanantly charged

Answer 16

because of covalent bonding via disulfide bridge, since it is permamantly charged it cant get backk out of the parietal cells, so acts specifically on them

Question 17

why is there maximum conversion to sulphenamide

Answer 17

due to the steep proton gradient caused by H+,K+ ATPase enzyme

Question 18

omeprazole final active form is what

Answer 18

sulphenamide as a permenantly charged quaternary ammonium salt

Question 19

how does sulphenamide stop production of acid

Answer 19

it reacts with thiols on the H+.K+ ATPase , which forms a stable disulphide complex. No more acid can be produced until a new eznyme is made - this results in a long duration of inhibition of gastric acid production

Question 20

uncharged omeprazole is absorbed from

Answer 20

the small intestine, into circulation and then diffuses into the parietal cells

Question 21

why is OM given in a hard gelatine capsule

Answer 21

to ensure it doesnt convert to sulphenamide in the stomach

Question 22

what dose of OM stops gastric acid production for at least 4hrs

Answer 22

80mg

Question 23

dose for duodenal ulcer vs gastric

Answer 23

bost 20mg, 2-4 weeks for duodenal, 8 weeks for gastric

Question 24

is the s or r enantiomer more effective at inhibition

Answer 24

s - esomeprazole

Question 25

how does the enteric coating break

Answer 25

stable in low pH , but when it enters the duodenum with high pH it swells and breaks down.

Question 26

functional group hidden on the chiral centre of omeprazole is

Answer 26

lone pair of electrons sitting on the sulfur

Question 27

why does sulfenamide have a permanant positive charge

Answer 27

due to the n+, has pi pi bonds => trapped