Drugs Modulating Intestinal pH Physiochemical Properties

Question 1

Result of excess acid production

Answer 1

Dyspepsia. Chronic dyspepsia results in GORD. May result in esophageal cells being differentiated into goblet cells due to exposure to acid.

Question 2

What happens to drugs in stomach

Answer 2

Digested by pepsin and absorption of acidic drugs

Question 3

Antacids Outline

Answer 3

Neutralisation of stomach contents by acting as a buffer (doesn’t effect cells). Provides rapid-acting temporary relief

Question 4

Types of Antacids

Answer 4

Bicarbonate (K Na), Bicarbonate (Al Mg), Bicarbonate (Mg) and Bicarbonate (Ca Na)

Question 5

Bicarbonate Outline

Answer 5

Substance with a protonated group. Accepts a proton = increasing pH (neutralising acid). Conjugate base of carbonic acid and conjugate acid of sodium carbonate

Question 6

Relationship between amount eaten and chance of reflux

Answer 6

Increased amount ingested = more pressure in stomach = increased chance of reflux

Question 7

Alginic Acid Def

Answer 7

Polysaccharide from seaweed. Forms a viscous layer on top of stomach content to act as protective layer for esophagus. Raft mechanism requires high conc. Relieving effects aren’t strong

Question 8

Why is Histamine the receptor targeted by antagonists

Answer 8

Don’t target Ach as it’s a main signaler in body for NS. Chances of lethal consequences are high

Question 9

Where are receptors on parietal cells

Answer 9

Only on basolateral side, makes drug that act on the slow acting as they need to travel in circulation. No binding in stomach

Question 10

Where are H2 receptors located

Answer 10

Enterochromaffin like cells

Question 10

Interactions between Warfarin and Cimetidine

Answer 10

Compete for the same receptor. This reduces effectiveness of each drug resulting in complications

Question 11

Cimetidine Outline

Answer 11

H Donor = 3. H acceptor = 6. Log P = - 0.07. Ro5 = yes. BCS class 3. Chirality = racemic mixture

Question 12

H+ - K+ Pump Inhibition by Omeprazole Outline

Answer 12

Omeprazole specifically only targets K+-H+ pumps due to presence of 92 kDa catalytic subunit. This subunit is where omeprazole’s intermediate covalently (irreversibly) binds preventing confirmational change

Question 13

Omeprazole Mode of Action Outline

Answer 13

Administered as a prodrug with an enteric coating (therapeutically inactive). No action is stomach due to enteric coating. Once enteric coating wears away in blood (already absorbed) a nitrogen in structure becomes quaternity (permanently positively charged) in acidic enviorment of perietal cell’s canculli. Positive N+ forms a permeant covalent bond with 92 kDa subunit on H+-K+ pump. Poisons pump for 24 hrs

Question 14

Why do some drugs need enteric coating

Answer 14

Alkaline drugs without protection get ionised in acidic enviorment of stomach rendering them unable to be absorbed (degraded). The half life of alkaline drugs is shortened (thus made less therapeutically active)

Question 15

Multiunit Pellet Systems (MUPS) Outline

Answer 15

Drug is layered over a small insoluble seed and then covered with release altering coating. MUPs disperse very quickly in GIT as due to really small particle size they can leave the stomach before gastric emptying and due to large surface area are absorbed quickly. The less time spent in GIT = lower risk of degradation (ionisation)

Question 16

Enteric Polymers Examples

Answer 16

Methacrylic acid and Eudragit L (dissolves in acidic enviorments)

Question 17

MUPS Advantages

Answer 17

Rapid dissolution, uniform absorption, greater bioavailability, faster onset

Question 18

MUPS Disadvantages

Answer 18

Segregation and compaction

Question 19

Patent Evergreening Outline

Answer 19

Producing a secondary product not for improvement of efficacy but to make more money

Question 20

Why do slow metabolisers have a better bioavailability

Answer 20

Lower metabolic rate = less of the drug degraded by enzymes = more drug reaching systemic circulation unchanged = better bioavailability

Question 21

Omeprazole as a Racemic Mixture

Answer 21

S enantiomer is therapuetically active due to slower metabolism, R enantiomer is therapuetically inactive due to fast metabolism and receptor placement

Question 22

Differences between esomeprazole and omeprazole

Answer 22

Omeprazole is racemic mixture and esomeprazole is only S enantiomers. This results in esomeprazole being more therapeutically active at lower conc. Was this evergreening or for efficacy’s sake?

Question 23

Effects of modifying gastric pH

Answer 23

Effects liberation and absorption of acidic drugs. May make them less therapeutically active