Thermodynamic basis of drug action

Question 1

What must the drug be in, in order to leave the gastric tract?

Answer 1

Solution

Question 2

What forms can increase rate of solution?

Answer 2

Amorphous form

Question 3

What is thermodynamic solubility?

Answer 3

An innate property of the molecule.
Will vary at varying pH (ionisation improves aqueous solubility)

[Drug solution] [Drug solid]
–> precipitation

Question 4

What is thermodynamic solubility controlled by?

Answer 4

Gibbs free energy

Question 5

What is phase 1 of metabolism?

Answer 5

oxidation
• Aliphatic or aromatic hydroxylation
• N-, or S-oxidation
• N-, O-, S-dealkylation

Question 6

What are the main class of proteins involved in phase 1 metabolism?

Answer 6

Cytochrome P450s

- they carry out phase 1 oxidations in liver cells

Question 7

what is the rate of oxidation determined by?

Answer 7

Rate of oxidation is determined by the stereoelectronics of the oxidation AND
the concentration of the drug-CYP complex

Relative rate of oxidation
correlates with stability of
radical X

Question 8

What drugs are most likely to be rapidly cleared?

Answer 8

lipophilic drugs