Science Of Medicines

Question 1

What is the effect of increasing a surfactant molecule’s hydrocarbon chain and why?

Answer 1

• Longer chain = decreased CMC (micellisation occurs faster at lower surfactant conc)
• Due to larger non-polar region = able to solubilise more solute/drug (form larger micelles)

Question 2

What is the 2nd law of thermodynamics? And how does it explain why micellisation occurs spontaneously?

Answer 2

• 2nd law = The entropy of an isolated system will always increase over time.
• Micellisation occurs spontaneously because formation of micelles leads to an increase in overall entropy of the system.
• Before micellisation: Hydrophobic tails of surfactant molecules are exposed, causing for water molecules to form highly ordered structures around them (reduced entropy).
• After micellisation: Hydrophobic tails cluster together, reducing amount of SA with water, meaning more water molecules can be in disordered state (increasing entropy).

Question 3

How is the solubility of a weak acid drug affected by pH?

Answer 3

• At high pH: equilibrium shifts to favour ionisation (HA —> H+ + A-), increasing concentration of the drug’s soluble ionised form (A-), increasing solubility.
• At low pH: equilibrium shifts to favour formation of unionised form (H+ + A- —> HA), decreasing solubility
• Works in the opposite way for weak base drugs

Question 4

What does “molar solubility” (S.o) mean?

Answer 4

• Molar solubility is the maximum amount of the drug’s unionised form that can dissolve in water before it begins to precipitate.
• In equations, use as the [HA] or [B]
• Typical units = mol/L

Question 5

What is the Noyes-Whitney Equation and what does each variable represent?

Answer 5

Equation:

Question 6

How does the size of a drug particle influence its dissolution rate in GI fluid + its overall BA?

Answer 6

• The smaller the drug particle size, the greater surface area —> increasing dissolution rate in GI fluid —> therefore increasing absorption and bioavailability.
• However if too small = less stable and more likely to degrade

Question 7

Give two examples of where modification of a drug to decrease its water solubility may be ultimately beneficial for its bioavailability?

Answer 7

• Chloramphenicol palmitate: Masks bitter taste of plain chloramphenicol, improving patient compliance —> increasing BA.
• Erythromycin propionate: Less soluble than erythromycin, but protects from degradation in GI fluid, increasing overall absorption in GI tract and therefore BA.

Question 8

What is the fraction of an ionised base equation?

Answer 8

Question 9

What is the fraction of ionised and unionised acid equation?

Answer 9

Question 10

What are 3 sites of digestion in the GI tract?

Answer 10

• Mouth
• Stomach
• Small intestine

Question 11

What is the purpose of the enteric coating of a drug?

Answer 11

• Protects drug from degradation within the acidic conditions of the stomach.
• Allows for delayed/targeted release of the drug, ensuring absorption takes place at desired site.
• Prevents stomach irritation

Question 12

What are the anatomical surfaces of the liver?

Answer 12

• The diaphragmatic surface = the upper surface of the liver
• The visceral surface = the lower surface of the liver, contains the gall bladder

Question 13

What happens during Phase II metabolism?

Answer 13

• Involves the conjugation of substituent group onto a tag (added during phase I) of the drug molecule.
• Substituent group = hydrophilic, so increases drug’s water solubility —> making it more easily excreted

Question 14

What is the consequence of impaired Phase II metabolism?

Answer 14

• Increased risk of drug toxicity or adverse effects as body can’t effectively convert drug into inactive metabolites.

Question 15

What is the renal drug excretion equation?

Answer 15

Total excretion = Filtration (into glom.) + Secretion (into tubules) - Reabsorption (back into bloodstream)

Question 16

What is Lipinski’s rule of 5?

Answer 16

• LogP =< 5
• MW =< 500Da
• Have =< 5 H-bond donors (OH and NH)
• Have =< 10 H-bond acceptors (O and N atoms)

Question 17

What is C.ss?

Answer 17

• Concentration of drug during “steady-state” phase of IV infusion => the conc of drug during plateau stage, after long-time of infusion.

Question 18

How do you calculate the concentration of a drug any time after an IV infusion is stopped?

Answer 18

• After infusion is stopped, situation becomes equivalent to IV bolus, therefore: C = C.o - e^-kt
• C.o = value of C at the time infusion was stopped.

Question 19

If a patient needs to immediately reach a certain dose of drug and then maintain a steady concentration, what should you do?

Answer 19

• An IV bolus loading dose followed by IV infusion
• 1) Administer IV bolus dose of the drug to achieve C.required without delay
• 2) Then start an IV infusion to maintain a constant required C.ss

Question 20

What is the IV bolus dose equation? (NOT given on equation sheet)

Answer 20

• IV Bolus Dose = C.required x V.d

Question 21

What is the IV infusion rate equation?

Answer 21

• R = C.ss x Cl
• Cl = k x V.d

Question 22

What are the properties of preservatives in solutions?

Answer 22

• They have a broad spectrum of antimicrobial activity
• More chemically/physically stable than API (greater shelf-life)
• Low toxicity (i.e. benzoic acids and their salts = 0.1-0.3% only)

Question 23

What are the factors that affect the efficacy of preservatives in solutions?

Answer 23

• pH of formulation: if preservative is in its unionised form, gives solution anti-microbial properties, increasing efficacy.
• Presence of micelles: if preservative molecules have lipophilic properties, they are more likely to be partitioned into micelles => decreasing the conc of available preservative in solution (decreasing efficacy).
• Presence of hydrophilic polymers: free conc of preservative in solution decreases in the presence of hydrophilic polymers (i.e. methyl cellulose).