Pharmacokinetics I Flashcards
What 3 things does the effect of a drug depend upon?
1) Mechanism of action and effects on cellular proteins
- Receptors
- Ion channels
- Enzymes
- Transporters
2) Physiochemical properties
3) Concentration
What are the physiochemical properties of a drug?
- Affinity
- Efficacy
What are the 4 considerations of concentration of a drug?
ADME
- Absorption
- Distribution
- Metabolism
- Excretion
What are ‘pharmacokinetics’?
The factors which come together to regulate the CONCENTRATION of the drug in the body
and therefore the concentration at the SITE of action
ADME
Why must we be aware of the pharmacokinetics of a drug?
In order to look at the possible effects of the concentration of the drug in different parts of the body
In order to know what the concentration will be at the site of action
Helps to understand possible side effects and also know if the drug will be effective
How are drugs mainly transported around the body?
In the cardiovascular system
What can happen to the distribution of the drug if the CV system is damaged?
- Impact on distribution and absorption into the different compartments of the body
How do drugs get across the various plasma membranes in 4 ways?
1) Diffuse through the lipid bilayer
2) Through aquaporins
3) HIjack carriers
4) Pinocytosis
What is pinocytosis and what is it important for?
- Cell engulfs extracellular fluid and internalises it
- Large peptides and antibodies
Why is the movement of drugs through aquaporins limited?
Drugs are normally too large to do this
What chemical properties determine how well a drug can diffuse through the membrane?
- Lipid solubility
- Diffusivity
What is the lipid solubility of a drug defined by?
The partition coefficient
What does a high partition coefficient mean and what molecules normally have this?
Very efficient at entering into the lipid compartment
Usually non-polar
When is a high partition coefficient beneficial?
Drugs used in the CNS - can cross the blood brain barrier
What is the disadvantage of a high partition coefficient?
More rapidly filtered by the kidney - quicker elimination
What is diffusivity defined by?
The diffusion coefficient
What is the diffusion coefficient proportional to?
- The molecular weight of the drug
1/√molecular weight
Which molecules are slower to equilibrate in lipids and why?
- Large molecular weight as diffusion coefficient = 1/√molecular weight
- Smaller diffusivity
What 4 things influence drug absorption into the body?
1) Site and method of administration
2) Molecular weight
3) Lipid solubility
4) pH and ionisation