Drug Absorption

Question 1

Pharmacokinetics:
What does ADME stand for? What does each mean?

Why is it important when choosing a drug?

What determines the amount of drug in circulation?

Answer 1

• • Absorption; unchanged drug enters circulation
  • Distribution; dispersion of drug around body
  • Metabolism; transformation of drug into daughter compounds
  • Excretion; removal of drug and its metabolites
• Important in determination of onset speed, duration of action, and potential problems
• Supply rate, Distribution, Excretion

Question 2

What are the types of ways to give a drug?

What guides the choice of which way to give a drug?

What is Bioavailability?

What are the biological barriers during absorption?

What are the 2 types of ways a drug moves past a cell?

Answer 2

• IV, Inhalation, Subcutaneous, IM, Oral
• Bioavailability, Speed of onset, Convenience, Side-effects
• % of administered drug that enters the blood
• Drugs to cross layers of semi-permeable, lipophilic cell membranes
• Transcellular (through cell), Paracellular (between cells)

Question 3

What determines how permeable a drug is?

What affects the extent of ionisation?

What is the Henderson-Hasselbach equation predict? What will occur with acidic and basic drugs?

Which drugs are absorbed more effectively?

Which type of drug is efficiently absorbed in the STOMACH?

Why are Basic drugs better absorbed in the INTESTINES?

Answer 3

• Ionisation, Lipid solubility
• pH of environment, Acid-base dissociation constant
• Extent of ionisation;
  o Acidic drugs - ↓pH = ↓Ionisation
  o Basic drugs - ↑pH = ↑Ionisation
• • Non-ionisable, lipophilic drugs absorbed; to diffuse across membranes, drug must be uncharged
• Acidic drugs
• Large surface area compensates for the low absorption efficiency

Question 4

What is the Lipinski Rule?

Answer 4

Orally-active drug likely has no more than one violation of the following;
o Molecular Weight <500 da
o ≤ 5 H-bond donors
o ≤ 10 H-bond acceptors
o Log P < 5 (Partition coefficient)