2.1.1 Clinical Pharmacokinetics and Pharmacodynamics I Flashcards
What is pharmacokinetics?
What effect the body has on drugs administered
What are the 4 principles of pharmacokinetics?
Absorption
Distribution
Metabolism
Excretion
ADME
What is the importance of pharmacokinetics?
Predicts toxicity
Allows us to predict effects of adding another drug
In the UK what agency is responsible for pharmacokinetics?
MHRA
Medicines & Healthcare products Regulatory Agency
What are the key factors when considering pharmacokinetics?
Bioavailability
Half-life
Drug elimination
Inter-subject variability
Drug-drug interactions
What is the purpose of assessing pharmacokinetics?
Safe dose
Optimal plasma concentration
Effects the correct tissues
What can pharmacokinetics be affected by?
- Renal function
- Liver function
- Cardiovascular function
- GI function
- Lifestyle factors, smoking, drugs
What is bioavailability?
Measure of drug absorption, where it can be used
IV=100%
Other routes have a fraction of IV
What is bioavailability affected by?
Absorption
-Formulation
-Age
-Food
-Vomiting/ malabsorption
-Previous surgery (GI disrupted)
First Pass metabolism
-Metabolism before reaching systemic circulation
What happens to the concentration of drugs in the plasma if elimination is fast and doses are taken far apart from eachother?
Large fluctuations in concentration
What can we use to prevent such large fluctuations in plasma concentartion of drugs?
Modified release preparations
Plasma concentration becomes dependant on rate of absorption vs rate of elimination, stays within effective therapeutic range for longer
Can help with adherence
Why is it so important to maintain drug concentration levels in the plasma?
So that the drug reaches the target tissue
What factors affect therapeutic distribution?
Blood flow
-Poor perfusion = less drug
Lipophilicity and hydrophilicity
Protein binding- unable to bind to receptor if bound to protein
What do acidic drugs tend to bind to?
Albumin
What do basic drugs tend to bind to?
Glycoproteins
What do hormones bind to?
Globulins
What is volume of distribution (Vd) ?
How much the drug spreads out within the body
High Vd- spread to more tissues, e.g. fats therefore lower plasma concentration
Low Vd- spread to fewer tissues, higher concentration within the plasma
When can drugs bind to receptors?
When they are ‘free drugs’
What can happen if displacement of a drug from a binding site occurs?
Protein binding drug interaction
When is drug displacement from a receptor clinically important?
If its highly protein bound
Narrow therapeutic index
Low Vd
If a second drug is added which displaces the first drug from binding proteins what will happen?
More free first drug to elicit a response
Can potentially cause harm as there could be too much of the initial drug
When can increased initial drug concentration due to displacement from protein be more concerning?
Pregnancy (fluid balance) as less protein available in first place
Renal failure- acidic drugs may not bind to protein
Hypoalbuminaemia- less albumin to bind in the first palce
What is apparent volume of distribution?
Proportionality factor
How much drug given to patient vs how much is actually in the plasma
How do you work out Apparent Volume of Distribution?
Example of AVd
Small apparent Vd vs Large
Small- suggests drug confined to plasma and extracellular fluid
Large- suggests drug distributed throughout tissues
Eventually as drug is metabolised more will become free and shift to plasma
What is the clinical relevance of Vd?
We can use it to work out dose sizes
