Lecture 4: Pharmacokinetics 1

Question 1

What are the routes of drug administration?

Answer 1

1. Local: topical
2. Systemic: Enteral (oral, sublingual, rectal) and \Parenteral (injections)

Question 2

Do oral drugs go through first pass metabolism?

Answer 2

• Some do, but not all
• For most oral drugs greatest abosorption is not in stomach but later in the small intestine

Question 3

Describe the journey of an oral drug

Answer 3

• Drugs absorbed from the stomach and intestine
• Drug travels to the liver via hepatic portal vein before reaching circulation and site of action

Question 4

What are the drawbacks of the oral drug route?

Answer 4

• Convenient but often 0.5-1hr delay in absorption
• Drug exposed to gastric acid, digestive and bacterial enzymes
• Possibility of poor GI absorption and/or first pass metabolism before reaching site of action

Question 5

What enteral routes of administration avoid first-pass metabolism and why?

Answer 5

• These routes avoid first pass metabolism as the blood drains into general circulation and not via hepatic portal vein
  1. Buccal
  2. Sublingual
  3. Rectal

Question 6

Do parental routes avoid first pass metabolism?

Answer 6

• They avoid both GI tract and first pass metabolism

Question 7

Which of these parental routes absorb drug the fastest (list fast - slow): intravenous (IV), intramuscular (IM), Subcutaneous (SC)

Answer 7

• Intravenous (instantaneous)
• Intramuscular (intermediate)
• Subcutaneous (very slow)

Question 8

What lipid membranes could drugs need to penetrate to reach their site of action?

Answer 8

• Plasma membranes of target cells
• Epithelial lining of GI, respiratory tract
• Endothelial lining of blood vessels at BBB or placental barrier

Question 9

How do the following drugs cross membranes:
1. Lipid soluble
2. Water soluble
3. Drugs with molecular weight >200

Answer 9

1. Lipid soluble: diffusion through lipid bilayer
2. Water soluble: diffusion through aqueous channel or carrier mediated transport
3. Mw >200: diffuse through intracellular junctions (tight junctions) between cells

Question 10

What does Fick’s law say passive diffusion across a membrane depends on? (5 points)

Answer 10

• Concentration gradient
• Area of membrane available for diffusion
• Thickness of membrane
• Permeability of membrane
• Lipid solubility of drug

Question 11

What is the PKA ratio?

Answer 11

The ratio of drug when 50% is ionised and 50% non-ionised

Question 12

Whats the effect of ionisation on drug absorption for:
1. Acid drug in acidic environment/basic drug in basic environment
2. Acid drug in basic environment/ basic drug in acidic environment

Is the drug ionised or not? Will it cross a lipid membrane?

Answer 12

1. Drug is non-ionised and WILL cross lipid membrane
2. Drug is mainly ionised and will NOT cross lipid membrane

Question 13

Give an example of the ionisation of a drug being useful in clinical treatment

Answer 13

e.g. If a patient overdosed on aspirin, you can alkalise the urine. Because the drug is in an ionised environment it wont cross the lipid membranes for absorption and will be excreted.

Question 14

What is bioavailability?
What is the value?

Answer 14

1. The fration or proportion of administered drug dose reaching the general circulation unchanged
2. F always between 0-1 (0%-100%)

Question 15

What affects the bioavailability of a drug? (4 points)

Answer 15

• Extent of drug solubility in local body fluids/tissues at the site of injection or administration
• Losses due to drug binding to local tissues or gut contents
• Extent of metabolism by local tissues
• Ability of drug to diffuse into local blood vessels