Drug Absorption

Question 1

What are the 2 main types of cellular absorption?

Answer 1

Transcellular and paracellular

Question 2

Most medicines move by which process?

Answer 2

• Most move by passive diffusion
• A few by facilitated diffusion
• Very few by active transport

Question 3

Which 2 factors determine permeability?

Answer 3

Lipid solubility and ionisation

Question 4

Drugs with what characteristics are most easily absorbed transcellularly?

Answer 4

Lipophillic and non-ionisable

Question 5

What equation predicts the extent of ionisation?

Answer 5

Henderson-Hasselbach equation:

pH = pKa when 50% ionised

Question 6

Describe the absorption of aspirin at the gastric mucosa.

Answer 6

• Aspirin = acetylsalicylic acid - weak acid
• Stomach pH = 1 - 99.7% HAsp absorbed across gastric mucosa
• Circulation pH = 7.4 - 99.9% Asp

Question 7

Describe where acidic and basic drugs are absorbed most efficiently and why.

Answer 7

• Acidic - in the stomach - pH 1
• Basic - in the intestine - pH 6.6-7.5
• Intestine - large surface area compensates for low absorption efficiency

Question 8

What are the Lipinski rules?

Answer 8

• A rule-based approach to ADME optimisation
• An orally active drug must not violate more than one of the following:
  
  • Molecular weight < 500
  • No more than 5 H-bond donors
  • No more than 10 H-bond acceptors
  • Log P < 5