L9 - Pharmacokinetics

Question 1

3 factors influencing drug targets

Answer 1

Mechanism of action and effects on cellular proteins
Physicochemical properties
Concentration

Question 2

Concentration depends on

Answer 2

Absorption
Distribution
Metabolism
Excretion

Question 3

Physicochemical properties

Answer 3

Affinity
Efficacy
Potency

Question 4

Drug absorption has to cross various barriers via

Answer 4

Simple diffusion (dissolves into the lipid bilayer)

Aquaporins (drug needs to be small and dissolved in water)

Transporter protein

Pinocytosis (cell engulfs ECF which contains drug)

Question 5

Most drugs are transported through?

Answer 5

Distributed by the cardiovascular system through the bloodstream

Question 6

Movement of drugs usually involves penetration of?

Answer 6

Lipid diffusion barriers

This determines where and for how long a drug will be present in the body after administration

Question 7

Physicochemical properties of drugs determined their ability to diffuse through lipids - lipid solubility

Answer 7

Partition coefficient
High coefficient means drug is efficient in entering lipid compartment
Non-polar drugs (needed so drugs can enter the CNS)

Question 8

Physicochemical properties of drugs determined their ability to diffuse through lipids - diffusivity

Answer 8

Diffusion coefficient
Describes how rapidly the drug moves
Proportional to the molecular weight of the drug
Drugs with high molecular weight have slower diffusivity

Question 9

Non-polar molecule diffusivity

Answer 9

Dissolve freely in lipids and penetrate cell membranes freely

• Increased rate of absorption from gut
• Increased penetration into brain and other tissues
• Increased renal elimination

Question 10

Factors influencing drug absorption

Answer 10

Route of administration
Molecular weight
Lipid solubility 
pH and ionisation 
Carrier mediated transport

Question 11

Route of administration - intravenous

Answer 11

By passes the gut, drug diffused straight into the blood supply
Fastest and most reliable way to control drug concentration in the plasma
Requires specialist knowledge

Question 12

Route of administration - intramuscular

Answer 12

By passes the gut
Has to bypass muscle barriers so slower rate of delivery
Useful for drugs with a high probability of getting metabolised in the gut
E.g. insulin

Question 13

Route of administration - intrathecal

Answer 13

Drug injected straight into the cerebrospinal fluid
Useful for drugs who need to act within the CNS and need precise concentration
E.g. local anaesthetic

Question 14

Route of administration - oral or rectal

Answer 14

Simplest and easiest route
Drug first encounters the gastrointestinal system
Impacted by the pH and enzymes found here
Most of the absorption occurs in the ileum of the small intestine – high surface area
Additional perfusion system – portal blood system
- Will deliver the drug directly to the liver
- Is important as it is where most drugs are metabolised

Question 15

Route of administration - percutaneous

Answer 15

Skin patches used to absorb drug straight through the skin
However, hard as the skin is typically impermeable
- Drug needs to be very non-polar
- Typically hormonal drugs

Question 16

Route of administration - inhalation

Answer 16

Restricted to 2 classes of drugs

• Those acting only in the lung – asthma
• General anaesthetic

Question 17

Molecular weight

Answer 17

Affects rate of diffusion

Question 18

Lipid solubility

Answer 18

Ability to cross lipid membrane by diffusion

Question 19

pH and ionisation

Answer 19

Many drugs are weak acids or bases
Weak acid = HA H+ + A-
Uncharged drug can cross lipids (undissociated form)
Charged drug cannot cross lipids (dissociated form)
At low pH (acid environment)
- Equation pushed left – drug in undissociated form

Question 20

Carrier mediated transport

Answer 20

Polar molecules (sugars, amino acids, metal ions) dependent upon saturation and competitive inhibition

Question 21

Aspirin as an example of the effect of pH

Answer 21

In the stomach – pH of 3
- Most of drug in its undissociated form
- Rapid diffusion across lipid barriers
In the plasma – pH of 7
- Less of drug in undissociated form
- Concentration of drug will rise relative to the acidic compartment
- Trapped because it is dissociated and cannot diffuse
In the urine – pH of 8
- Most of the drug is in its dissociated form
- Drug becomes increasingly trapped

Question 22

pKa

Answer 22

= pH + log10(HA/A-)

Question 23

Aspirins pKa

Answer 23

Weak acid - pKA of 3.5

Question 24

Weak acids become trapped in?

Answer 24

Basic compartments

E.g. renal tubules

Question 25

Urinary acidification causes?

Answer 25

It slows excretion of weak acids
Increasing plasma pH (sodium bicarbonate) causes weak acid drugs to be extracted from CNS back into plasma where they get trapped
- Decreased neurotoxicity
- E.g. following poisoning with aspirin