Pharmacokinetics Concepts Flashcards
What is pharmacokinetics?
The study of movement of a drug into and out of the body - the study of what the body does to the drug
What is pharmacodynamics?
The study of drug effect and the mechanisms of action - what the drug does to the body
What is pharmacogenetics?
The effect of genetic variability on the pharmacokinetics, or the dynamics of a drug on an individual
What are the main processes involved in drug therapy?
- Pharmaceutical process
- Pharmacokinetic process
- Pharmacodynamic process
- Therapeutic process
What question is asked when considering the pharmaceutical process?
Is the drug getting into the patient
What question is asked when considering the pharmacokinetic process?
Is the drug getting to its site of action
What aspects does the pharmacokinetic process consist of?
- Absorption
- Distribution
- Metabolism
- Elimination
What question is being asked when considering the pharmacodynamic process?
Is the drug producing the required pharmacological effect?
What question is being asked when considering the therapeutic process?
Is the pharmacological effect being translated into a therapeutic effect?
Draw a diagram illustrating the relationship between pharmaceutical process, pharmacokinetic process, pharmacodynamic process, and therapeutic process
Draw a diagram illustrating the stages of ADME in relation to a time-concentration graph
What is meant by oral bioavailability?
The fraction of a dose which finds its way into a body compartment, usually the circulation
What is the bioavailability for an intravenous bolus?
100%
How is the bioavailability worked out for all other routes apart from IV?
You compare the amount reaching the body compartment by that route with intravenous bioavailability
Give the equation for the calculation of oral bioavailability?
= area under the curve (oral) / area under the curve (IV)
What is meant by area under the curve when calculating oral bioavailability?
The area under the curve of plasma concentration x time post dose - this is the total drug exposure
What factors affect bioavailability?
- Drug formulation
- Age
- Food
- Vomiting/malabsorption
- Fire pass metabolism
What is first pass metabolism?
Any metabolism occuring before the drug enters the systemic circulation
In what locations can first pass metabolism occur?
- Gut lumen
- Gut wall
- Liver
What produces the first pass metabolism effect in the gut lumen?
- Gastric acid
- Proteolytic enzymes
- Grapefruit juice
What drugs are affected by the first pass metabolism in the gut lumen?
- Benzylpenicillin
- Insulin
- Ciclosporin
What produces the first pass affect in the gut wall?
P-glycoprotein efflux, which pumps drugs out of the intestinal entrocytes and back into the lumen
What drugs are affected by first pass metabolism in the gut wall?
Ciclosporin
What produces the first pass effect in the liver?
Drugs get oxidised and conjugated
What drugs are affected by the first pass effect in the liver?
- Propanolol
- Morphine
What does the distribution of a drug refer to?
Its ability to ‘dissolve’ in the body
What are the two key factors associated with drug distribution?
- Protein binding
- Volume of distribution
When are many drugs bound to circulating proteins?
Once they are in the systemic circulation
Give 4 proteins that bind drugs in the systemic circulation?
- Albumin
- Globulins
- Lipoproteins
- Acid glycoproteins
What kind of drugs does albumin bind?
Acidic drugs
What kind of drugs do globulins bind?
Hormones
What kind of drugs to lipoproteins bind?
Basic drugs
What kind of drugs do acid glycoproteins bind?
Basic drugs
What binding state must drugs be in to have a pharmacological effect?
Most must be unbound (free)
Why must most drugs be unbound in order to have a pharmacological effect?
Because only the fraction of the drug that is not protein-bound can bind to the cellular receptors, pass across tissue membranes, gain acess to cellular enzymes etc
What does the level of free drug determine?
The action of the drug at its target receptor, and its elimination
What can displacement of drugs from binding sites produce?
Protein binding drug interactions
What affect may changes in protein binding have?
Can cause changes in drug distributino
When are changes in protein binding important?
If one of three criteria are met;
- High protein binding
- Low Vd
- Narrow therapeutic ratio
What factors affect protein binding?
- Hypoalbuminaemia
- Pregnancy
- Renal failure
- Displacement by other drugs
Regarding distribution, what is true of drug that is not bound to plasma proteins?
It is available for distribution to the tissues of the body
Are drugs found in body fluids, or in tissues?
Some are distributed only to body fluids, whereas others are found extensively in body tissues
What is volume of distribution?
A measure of how widely a drug is distributed in body tissues
Give the equation for calculating volume of distribution?
= dose / [drug]10
Where is volume of distribution a useful measure?
Useful in understanding dosing regimes
What is half life proportional to?
Vd and clearance
What is the body fluid distribution in a 70kg man?
- Intracellular space 55% (23L)
- Intravascular space 12% (5L)
- Interstitial space 33% (14L)
What can tissue distribution be affected by?
- Specific receptor sites in tissues
- Regional blood flow
- Lipid solubility
- Active transport
- Disease states
- Drug interactions
What is a drug initially metabolised by?
Phase 1 enzymes
What happens once a drug has been metabolised by phase 1 enzymes?
CYPs perform a variety of functions
What functions are performed by CYPs?
- Oxidation
- Dealkylation
- Reduction
- Hydrolysis
What happens after CYPs have performed their functions on drugs?
It either;
- Gets metabolised by phase II enzymes
- Go to the kidney
- Go to the gallbladder
What happens to drugs metabolised by phase II enzymes?
They then get conjugated with;
- Glucoronide
- Sulphate
- Glutathione
- N-acetyl