Pharmacokinetics

Question 1

Define pharmacokinetics.

Answer 1

How drugs move around the body.

Question 2

All psychoactive drugs used to treat disorders of the CNS must enter the brain. Why is the route of administration important?

Answer 2

It affects the number of membranes a drug must cross, and also how much is lost or metabolised before it can act on its target.

Question 3

What is the blood-brain barrier?

Answer 3

A highly selective semi-permeable membrane that separates the blood from the extracellular brain fluid. This blocks entry of cells and large molecules to the CNS.

Question 4

List 3 advantages of oral administration.

Answer 4

1. Easy for patients to self-administer
2. Sterile
3. Safer than intravenous administration

Question 5

Why is oral safer than intravenous administration?

Answer 5

Due to first pass metabolism: orally administered drugs must first cross the digestive system. Blood from the gut flows to the liver before the rest of the body. The liver filters out toxic chemicals. OD’ing on oral drugs is safer than intravenous for this reason.

Question 6

Give 2 disadvantages of oral administration.

Answer 6

1. First pass metabolism means that much of the drug is lost before it has a chance to act, thus higher doses are required
2. The effects are hugely variable between individuals

Question 7

What are the disadvantages to intravenous administration. List 3.

Answer 7

1. Not easy to self-administer
2. High risk of infection unless performed in a clinical setting
3. Higher risk of OD as drug directly enters the blood.

Question 8

Body pH has an effect on drug metabolism. What is Pka?

Answer 8

The partition coefficient: the pH at which 50% of a substance is ionised.

Pka denotes the lipid solubility of a drug.

Question 9

Why must drugs be lipid soluble?

Answer 9

So they can diffuse across the lipid bilayer of cell membranes.

Question 10

If the environmental pH is lower than the Pka of a drug, what happens?

Answer 10

The drug will be protonated. Protonation is required for transport so the drug will be up-taken into cells.

Question 11

Give an example of Pka affecting absorption of a real drug.

Answer 11

Aspirin has a Pka of 3.5. The pH of the stomach is 2. Aspirin is thus protonated and up-taken. Once aspirin is inside cells, that have a higher inner pH, it becomes trapped there. Uptake is self-perpetuating.
The small intestine has a higher pH so no aspirin is absorbed there.

Question 12

What is the half-life of a drug?

Answer 12

The time taken for the concentration to reduce by 50%.

Question 13

Drugs are always more dangerous than their metabolites. True or false?

Answer 13

False: some drug metabolites are more toxic and longer-lasting than the initial drug itself.

Question 14

What might cause a spike in the blood concentration of a drug?

Answer 14

Enzyme saturation.

Question 15

List 3 ways drugs can be lost from the body.

Answer 15

1. Renal function
2. Bile production by the liver
3. Sweating

Question 16

Urine pH can cause reabsorption of a drug into the blood. True or false?

Answer 16

True.

Question 17

Define first order kinetics.

Answer 17

Higher concentration leads to more rapid elimination from the body.

Question 18

Define zero order kinetics.

Answer 18

Metabolism is constant regardless of drug concentration.

Question 19

Define biotransformation.

Answer 19

The addition of groups, like carbohydrates, to drug molecules that make them hydrophilic and unable to cross the lipid bilayer.

Question 20

Give 2 examples of internal storage depots.

Answer 20

1. Adipose tissue

2. Bone

Question 21

Why do some drugs take multiple doses to take effect?

Answer 21

They must first equilibrate across the storage depots before they become active in the body.

Question 22

Similar drugs are stored in the same storage depots. True or false?

Answer 22

True.

Question 23

Why do drug effects vary between individuals?

Answer 23

The amount of storage tissue varies, as do rates of metabolism.