Chemical basis of drug action

Question 1

What is a buffer made up of?

Answer 1

Mixture of strong acid + weak base or weak acid + strong base

Question 2

Buffer

Answer 2

Resist changes to pH on addition of further acid or base

Question 3

What is a prodrug + give an example

Answer 3

Drug needs to be activated to become the active drug species

e.g. Omeprazole

Question 4

Proton pump inhibitor

Answer 4

Inhibit proton pump in parietal cells

Binds irreversibly to the pump

Question 5

Amphoteric H2 - receptor antagonist

Answer 5

Famotidine

Question 6

Examples of H2 - receptor antagonist

Answer 6

Cimetidine
Ranitidine
Famotidine
Nizatidine

Question 7

What is the acidity/basicity of H2RAs

Answer 7

Cimetidine, Ranitidine + Nizatidine = weakly basic

Question 8

Journey of omeprazole

Answer 8

Stomach -=> duodenum => Blood => Parietal cells

Question 9

Stability of omeprazole in acid

Answer 9

Unstable - it undergoes reaction to form prodrug and then binds irreversibly to proton pump

Question 10

What produces urease enzyme

Answer 10

Helicobacter pylori

Question 11

Function of urease enzyme

Answer 11

Protects bacterium from acid by producing NH3 which neutralises stomach acid

Question 12

Similarities 13C + 12C

Answer 12

Naturally occuring

non-radioactive isotopes of carbon

Question 13

Agonist at H2-receptor

Answer 13

Histamine

Question 14

What is imidazole ring responsible for in H2RA

Answer 14

ADR

Question 15

What is furan / thiazole ring responsible for in H2RA

Answer 15

• increases selectivity + potency of antagonism at H2 receptors
• reduces interaction with cytochrome

Question 16

What does histamine stimulate

Answer 16

• Acid secretion by parietal cells

- interacts with H2 receptors

Question 17

When does the greatest secretion occur

Answer 17

Within 1 hour of eating

Question 18

Acid secretion is _______ the volume of the meal

Answer 18

twice

Question 19

What type of polymer is simeticone

Answer 19

Silicone polymer

Question 20

Use of simeticone

Answer 20

Alters (lowers) surface tension of small bubbles + fuse them to form larger bubbles so gas in stomach can be easily lost
Relieves trapped wind

Question 21

Calcium ions interact with _____________ and aid ___________ in the polymer

Answer 21

Alginate / alginic acid

Cross-linking

Question 22

How does alginic acid precipitate as a gel

Answer 22

When pH drops below 3.5

Question 23

What happens when alginic acid is a gel

Answer 23

It absorbs water and swells forming a raft

Question 24

Where is alginic acid extracted from

Answer 24

Brown seaweeds

Question 25

Examples of weakly basic drugs

Answer 25

Ranitidine, Cimetidine (H2RAs except Famotidine)

Question 26

Ionised species of weakly basic drugs will be...

Answer 26

Hydrated + more soluble

Question 27

Weak base HH-equation

Answer 27

pKa = pH + log BH+ / B

Question 28

Examples of weakly acidic drugs

Answer 28

Phenobarbital, phenytoin, Warfarin, NSAIDs

Question 29

Ionised species of weakly acidic drugs will be...

Answer 29

Hydrated + more soluble

Question 30

Weak acid HH-equation

Answer 30

pKa = pH + log HA / A-

Question 31

pKa of an acid is the pH at which it is...

Answer 31

Half dissociated

Question 32

Equation to calculate pH of a weak base

Answer 32

1/2pKw + 1/2pKa + 1/2logB

Question 33

Equation to calculate pH of a weak acid

Answer 33

pH = 1/2pKa - 1/2logHA

Question 34

Main active ingredients in raft forming medicines

Answer 34

Sodium alginate Sodium bicarbonate Calcium carbonate

Question 35

Source, structure + solubility of Alginic acid

Answer 35

From brown seaweeds Polymer composed of sugar monomer units (mixture of polyuronic acids) Molecular weight over 150,000 daltons Insoluble in water

Question 36

Solubility of alginic acid + alginic salts

Answer 36

Alginic acid = insoluble | Alginate salt = water soluble

Question 37

Polyuronic acids composed of

Answer 37

D-mannuronic L-guluronic acid - responsible for solubility is COOH

Question 38

Mechanism by which alginic acid and alginate salts form a raft

Answer 38

If pH drops below 3.5 (approx. pka), alginic acid precipitates as a gel Gel swells + absorbs water Raft is formed

Question 39

Explain how + why carbon dioxide forms; in the creation + properties of raft

Answer 39

Many alginate based meds contain bicarbonate / carbonate In acid: - bicarbonate/carbonate produce CO2 - soluble alginate reacts to form insoluble alginic acid precipitate - gel traps CO2 gase, produce low density raft that can float on stomach contents

Question 40

Mechanism by which calcium affects structure + properties of raft

Answer 40

Calcium cations interact with alginate + aid cross linking in the polymer Increases viscosity - BP raft forming ability method = evidence that calcium cations increase raft strength

Question 41

Main active ingredient in anti-foaming agents

Answer 41

Simeticone

Question 42

Chemical + physical property simeticone (anti-foaming agent)

Answer 42

Dimethicone (polydimethylsiloxane) + silica (also activated dimethicone) Silicone polymer Alter (lower) surface tension of small gas bubbles so they fuse to form larger bubbles Allows gas in stomach to be easily lost It relieves trapped wind + bloating in dyspepsia (win-eze)

Question 43

Common active ingredients in antacid medicine

Answer 43

``` Sodium bicarbonate Potassium bicarbonate Calcium carbonate Sodium carbonate Magnesium carbonate Magnesium hydroxide Aluminium hydroxide ```

Question 44

Heterocycle

Answer 44

Rings that contain carbon atoms and other non- carbon atoms

Question 45

mEq

Answer 45

(30 x Mhcl) - (Vnaoh x Mnaoh) = amount consumed by medicine = HCl - amt NaOH to reach pH 3.5 =mmol

Question 46

Ideal characteristics of an antacid

Answer 46

- Acts locally - insoluble in water + not absorbed into circulation - pH of 3-5 - exerts effects swiftly with good duration of action - does not produce large volumes of gas when reacting with HCl - not cause laxative effects/constipation

Question 47

Why is it advantageous to combine a number of antacids in one medicine

Answer 47

- optimise rate of onset of action - duration of action - range of pH reached - moderate constipating + laxative effects

Question 48

What salts have constipating effects

Answer 48

Calcium + aluminium

Question 49

What salts have laxative effect

Answer 49

Magnesium

Question 50

Common chemical features in H2RA

Answer 50

Furan, thiazole + imidazole

Question 51

Common chemical features in NSAIDs

Answer 51

Benzene + Carboxylic group

Question 52

Chemical reaction + mechanism of the irreversible inhibition by aspirin

Answer 52

Nucleophilic substitution + addition-elimination reaction - transesterification