option D- medicinal chemistry (D.4)

Question 1

what is gastric juice composed of?

Answer 1

• water
• salts (mostly KCl and NaCl)
• hydrochloric acid
• enzymes (pepsins)

Question 2

what are pepsins secreted by and what are they responsible for ?

Answer 2

cells in the stomach lining; they are responsible for the breakdown of proteins into peptides and individual amino acids

Question 3

how does the body keep stomach conditions bearable?

Answer 3

some cells produce hydrogen carbonate ions (HCO3-) and gastric mucus to buffer the acid and prevent the gastric juice from digesting the stomach tissues

Question 4

what is the role of the hydrochloric acid in the stomach?

Answer 4

although the acid itself does not break down food molecules, it:

• denatures proteins
• provides an optimum pH for enzymes in the gastric juice
• acts as a disinfectant, killing harmful microorganisms ingested with the food

Question 5

define an active metabolite

Answer 5

the active form of a drug after it has been processed by the body

Question 6

what are antacids used for

Answer 6

to reduce the excess stomach acids by reacting with hydrochloric acid increasing the pH of gastric juice

Question 7

give examples of common antacids

Answer 7

calcium hydroxide, magnesium hydroxide, aluminium hydroxide, sodium carbonate and sodium bicarbonate

Question 8

how do antacids work?

Answer 8

they reduce the concentration of H+ (aq) ions and therefore increase the pH of gastric juice

Question 9

how can the acidity of gastric juice be controlled at the cellular level?

Answer 9

by targeting the biochemical mechanisms of acid production

Question 10

what is the secretion of acid in the stomach triggered by?

Answer 10

histamine (a derivative of amino acid histidine) that binds to H2-histamine receptors in the cells of the gastric lining

Question 11

what can be used top inhibit stomach acid production?

Answer 11

compounds such as ranitidine (Zantac)

Question 12

how does ranitidine (Zantac) function?

Answer 12

it blocks H2-histamine receptors and reduces the secretion of stomach acid. This provides short-term relief from symptoms of indigestion

Question 13

how do omeprazole (Prilosec) and esomeprazole (Nexium) work?

Answer 13

they reduce the production of stomach acid by inhibiting a specific enzyme, known as the gastric proton pump, which is directly responsible for secreting H+ (aq) ions into the gastric juice.

Question 14

how are proton pump inhibitors different to ranitidine?

Answer 14

they reduce the secretion of stomach acid for prolonged periods (up to 3 days)

Question 15

describe the similarity and difference between omeprazole and esomeprazole

Answer 15

they have the same molecular formula (C17H19N3O3S) but whereas omeprazole is a racemic mixture of both enantiomers (R-omeprazole and S-omeprazole), esomeprazole is a single enantiomer (S- omeprazole).

Question 16

how do the two enantiomers of omeprazole contrast to many other drugs?

Answer 16

show very similar pharmacological activity (refer to textbook for images)

Question 17

describe how omeprazole and esomeprazole work

Answer 17

• in their original form, they are inactive and do not interact with the gastric proton pump directly
• due to their low polarity they readily cross cell membranes and enter the intracellular compartments containing HCl acid
• in this acidic environment both enantiomers undergo a series of chemical transformations and produce the same active metabolites, which bind to the proton pump enzymes and inhibit the secretion of stomach acid

Question 18

why is the mechanism of action of omeprazole and esomeprazole beneficial ?

Answer 18

it increases the efficiency of both drugs and allows a reduced frequency of administration

Question 19

describe how the pH of gastric juice is different to the pH of other biological fluids

Answer 19

whereas the concentration of stomach acid varies by a factor of 100, the pH of other biological fluids remains relatively constant

Question 20

how is the stability of biological fluids achieved?

Answer 20

by the action of acid-base buffers, which can neutralise small amounts of strong acids and bases without significantly changing their pH.

Question 21

how do acid base buffers work?

Answer 21

they each contain two molecular or ionic species which differ by a single proton (H+)- conjugate acid base pairs

Question 22

in a conjugate acid base pair, the more protonated species is the ——-

Answer 22

conjugate acid

Question 23

in a conjugate acid base pair, the less protonated species is the ——-

Answer 23

conjugate base

Question 24

describe an acetate buffer

Answer 24

consists of ethanoic (acetic) acid, CH3COOH and ethanoate (acetate) anions, CH3COO-

Question 25

in buffer solutions both the conjugate acid and the conjugate base are —– and exist in ——

Answer 25

weak, equilibrium

Question 26

state the equilibrium equation for an acetate buffer

Answer 26

CH3COOH (aq) <-> CH3COO- (aq) + H+ (aq)

Question 27

what is the primary acid-base buffer system in the human body? give the TWO equilibrium equations for this

Answer 27

one that consists of carbon dioxide and hydrogen carbonate ions:

BASE CO2 . H2O <-> ACID HCO3- (aq) + H+ (aq)
pKa1= ~6

at a higher pH
ACID HCO3- (aq) <-> BASE CO32- (aq) + H+ (aq)
pKa2= ~10

Question 28

the ability of acid-base buffers to resist pH changes is —– and depends on ——

Answer 28

the concentrations and ratios of the conjugate acid and base in the solution

Question 29

when does an acid-base buffer reach its maximum efficiency and can neutralise the greatest amounts of strong acids or bases

Answer 29

pH=pKa

it can be used between pH=pKa±1 as outside this range the concentration of one of the buffer components becomes too low and the buffer loses its ability to maintain a constant pH of the solution