Introduction to Pharmacokinetics Flashcards
What does ADME stand for? What is its significance?
Absorption
Distribution
Metabolism
Excretion
This is the path of an orally administered drug.
What is the therapeutic window of a drug?
The difference between the effectrive concentration and toxic concentration.
What is the difference between pharmacokinetics and pharmacodynamics?
Pharmacodynamics is how a drug affects the body.
Pharmacokinetics is how the body affects a drug.
What is the apparent volume of distribution?
What is its equation?
The volume of fluid required to dilute the absorbed dose to the concentration found in plasma.
AVD (volume) = dose (mass) / plasma concentration (mass/volume)
If a drug is heavily tissue bound, will the AVD be greater or lower than if a drug is heavily plasma bound?
Greater, as the plasma concentration of a heavily tissue bound drug will be lower, so a greater dilution will be required to make the sample concentration equal to the plasma concentration.
What are enteral routes of administration?
Oral or rectal routes.
What are parenteral routes of administration?
Subcutaneous, intramuscular or intravenous routes.
What are percutaneous routes of administration?
Inhalation, sublingual, or topical routes.
List 5 factors that affect rate of absorption of drugs.
1 - Route of administration.
2 - Blood flow at site of administration; surface area.
3 - Dose of drug.
4 - Active vs passive diffusion through the membrane.
5 - Drug solubility in water and in lipids.
List 3 factors that affect distribution of drugs.
1 - Lipid solubility and diffusion barriers.
2 - Tissue binding.
3 - Plasma protein binding.
What is the most common plasma protein that drugs bind to?
Albumin.
Where is first pass metabolism done?
In the liver.
What are biotransformation phases I and II?
Phase I - Oxidative, reductive and hydrolytic reactions
Phase II - Conjugation reactions, e.g. sulfation.
Where can biotransformation phases I and II be carried out?
- In the liver.
- In the skin.
- In the lungs.
Where can conjugation reactions, e.g. sulfation pathways, be carried out?
Basically anywhere in the body.
Where can oxidation by cytochrome p450 enzymes be carried out?
Mostly in the liver but also in microbiomes of the body.
What is a prodrug?
A drug that is inactive until metabolised.
List 3 examples of prodrug.
1 - L-DOPA
2 - Diazepam
-> desmethyldiazepam
3 - Tamoxifen
-> 4-hydroxy-tamoxifen
What are the two phases of first pass metabolism?
Phase I - Oxidation via cytochrome p450 enzymes.
- Addition of hydroxyl groups.
- Compounds become more hydrophilic.
Phase II - Conjugation reactions.
- Charged groups linked to compounds.
- Compounds EVEN MORE hydrophilic.
List 2 examples of groups that are linked in phase II conjugation reactions.
- Sulfates
- Glucuronidates
What is the name of the enzymes that conjugate sulfates to substrates?
Sulfotransferases.
What are the 7 points at which the available concentration of a drug changes, from administration to site of action?
1 - Total oral dose.
2 - Dissolved in GIT.
3 - Absorbed.
4 - In liver.
5 - General circulation.
6 - In tissues.
7 - At site of action.
List 4 pre-clinical outcomes from doing pharmacokinetics.
1 - Select compounds that have the maximum potential of reaching the site of action.
2 - Select the appropriate route of administration.
3 - Understand how the plasma concentration relates to efficacy and toxicity.
- Used to select safe dosage.
4 - Decide on the frequency and duration of dosing.
- Used to sustain drug at target.
What are the 4 steps of a pharmacokinetics study?
1 - Administer dose.
2 - Collect samples from blood, urine, bile and faeces at various times.
3 - Analyse for drug (spectroscopy or chromatography).
4 - Data analysis.
What is plasma half life?
The time taken for the drug plasma concentration to half.
