L10 - Pharmacokinetics II

Question 1

Factors influencing drug distribution

Answer 1

Major body compartments
Drug permeability 
Lipid solubility 
Binding of drug to plasma proteins
Partition into specific tissues

Question 2

Factors influencing drug distribution - major body compartment

Answer 2

Extracellular fluids

Plasma 4.5%

Interstitial fluid 16% (surrounds cells)

Lymph 1-2%

Intracellular fluids – 30-40%

Transcellular fluids – 2.5%

Fat – 20%

Question 3

Factors influencing drug distribution - binding of drug to plasma proteins

Answer 3

Albumin binds mainly to acidic drugs
Each albumin molecule can bind to two drug molecules
This is an issue if a large concentration of the drug is required
Means nonlinear concentrations of the drug in the blood

Question 4

Factors influencing drug distribution - partition into specific tissues

Answer 4

E.g. body fat (especially with non-polar drugs)
With low body fat – even a low dose will reach the brain very quickly and the effects will be seen for a long time
Also impacts on the rate of elimination of the drug

Question 5

Endothelial cells lining blood vessels in CNS form tight junctions which are?

Answer 5

Impermeable to water soluble molecules
- Antibiotics, chemotherapy drugs, biological drugs
Permeable to lipid soluble molecules
- Ethanol, caffeine

Question 6

Tight junctions can become leaky during?

Answer 6

Inflammation

E.g. treat Meningitis with intravenous dose of penicillin

Question 7

What is the chemoreceptor trigger zone?

Answer 7

An area of the medulla oblongata that receives inputs from drugs or hormones
Communicates with other structures to initiate vomiting
Antagonist blocks receptors in this zone
Antagonist is big enough so that it does not cross the BBB

Question 8

Drug must cross plasma membrane to be metabolized by?

Answer 8

Microsomal enzymes

• Cytochrome P450
• Alcohol dehydrogenase
• MAO

Question 9

Two biochemical reactions occur in the liver

Answer 9

Phase 1 catabolic reactions
- Can produce more reactive compound
Phase 2 synthetic (anabolic) reactions
- Involve conjugation to produce inactive product

Question 10

Changing enzyme induction can?

Answer 10

Lead to more efficient metabolism

Question 11

Drug metabolism

Answer 11

Some drugs (pro-drugs) only become active after metabolized 
Metabolism can alter or prolong pharmacological actions of a drug

Question 12

Elimination of aspirin - stage 1

Answer 12

Acted on by a cytochrome P450 enzyme

Question 13

Elimination of aspirin - stage 2

Answer 13

Reactive intermediate which is dangerous

in high quantities

Question 14

Elimination of aspirin - stage 3

Answer 14

Conjugation to produce an inactive product

Question 15

P450 enzymes

Answer 15

Human genome project has identified 57 genes coding for P450 enzymes
Different isoforms of P450 react with different drugs
P450 doesn’t only metabolise drugs it has other functions in the body
Inducers of P450 increase drug metabolism

Question 16

Drug excretion - renal excretion

Answer 16

Lost in urine
Penicillin cleared on single transit whereas diazepam cleared very slowly
Renal disease can affect drug clearance – toxicity
Glomerular filtration
Active tubular secretion
Passive diffusion

Question 17

Drug excretion - GI excretion

Answer 17

Faeces

Question 18

Drug excretion - lung excretion

Answer 18

Expired air

Question 19

What is pharmacokinetics?

Answer 19

Time course of drug concentrations attained in the body during and after dosing

Question 20

The time course of drug clearance

Answer 20

The time course of clearance follows a mono-exponential decay
The time course is determined by rate of metabolism and excretion

Question 21

Half-life of the drug is independent of?

Answer 21

Drug concentration

Question 22

Some drugs show saturation kinetics

Answer 22

Disproportionate increase in steady-state plasma concentration leads to clinical side effects and toxicity