Pharmacokinetics Flashcards
What are the 4 elements encompassed in pharmacokinetics?
Absorption
Distribution
Metabolism
Excretion
What is a concentration-time profile?
Where are the ADME processes most predominant on the concentration-time profile?
A measure of the concentration of a drug in the body over time
True or false, Absorption and metabolism/excretion cannot occur at the same time
False. As soon as a drug enters the body metabolism and excretion can begin
What drug qualities influence the movement of a drug?
Water/Fat solubility
- Absorption, distribution & excretion
- Especially important to movement across membranes
Chemical structure
- Susceptibility to destruction by metabolism
What is passive diffusion?
What drug properties will make drugs favour transcellular diffusion over paracellular diffusion?
Passive diffusion is the non-mediated, electrochemical gradient-driven movement of a substance through a membrane
Transcellular diffusion is favoured by small, lipid-soluble and non-ionised molecules
Paracellular diffusion is favoured by highly water-soluble molecules
What is facilitated diffusion?
What is an example of facilitated diffusion?
Facilitated diffusion is the carrier-mediated, electrochemical gradient-driven movement of a substance through a membrane
An example of this is organic anion transporters which are found in the kidneys, transporting organic anions into the proximal tubule
What is active transport?
Active transport is the channel-mediated, ATP-driven movement of substances against their electrochemical gradient
What is pinocytosis/endocytosis?
The envelopment of extracellular fluid (pinocytosis) or drug bound to cell surface receptor (endocytosis), forming a vesicle to transport inside the cell
What is absorption?
What does the rate of absorption determine?
What does the extent of absorption determine?
Absorption of a drug is the phase in which it’s moving from the site of administration to systemic circulation
The rate of absorption determines the speed of onset
- How rapidly the drug gets from the administration site to systemic circulation
The extent of absorption determines the duration of drug action
- How much administered drug enters general circulation (% bioavailability)
What is bioavailability dependent on?
First pass metabolism
Accumulation into local fat stores
Degradation by enzymes or pH
What factors influence oral absorption?
Interactions with food
e.g. tetracycline can form ionic complexes with calcium, impairing transport across membranes
Stomach emptying rate
- A faster rate speeds up absorption rate (Hunger, mild exercise)
- A slower rate slows down absorption rate (Hot meals, vigorous exercise, pain)
Intestinal motility
- Increased motility decreases time for absorption (e.g. diarrhoea)
- Decreased motility increases time for absorption (e.g. opioids, antidepressants)
What is bioequivalence?
Two drug formulations having similar rates and extents of absorption (80-125%)
What is distribution?
What affects the extent of distribution?
Distribution is the transport of a drug through systemic circulation and how well it moves into peripheral tissue
Distribution factors
- Lipid solubility
- pH/ionisation of the drug
- Protein binding
How does pH/drug ionisation affect distribution?
Ionised drugs can’t pass through membranes as easily, altering passive diffusion (ion trapping)
How does protein binding affect distribution?
Plasma proteins can bind to some drugs, trapping the drug in plasma (e.g. penicillins bind to albumin)
How is distribution measured?
The volume of distribution (Vd). It is an intrinsic property of the drug which is difficult to change without altering the drug itself
What are the two mechanisms of elimination?
Metabolism/biotransformation and Excretion
What sorts of drugs does metabolism usually affect?
Where do the byproducts of metabolism end up?
Metabolism typically acts on lipid-soluble drugs to make them more water-soluble
Metabolism byproducts usually end up back in the bloodstream
What sorts of drugs does excretion usually affect?
What happens to them during excretion?
Excretion typically acts on water-soluble drugs
No conversion happens to these drugs, they just get removed from the body
What are the ways drugs can be excreted?
Bile
Urine
Sweat
Breast milk
Exhaled air
Where does metabolism primarily occur?
The liver
What are the two main reactions in metabolism?
Functionalisation - Exposing a reactive group on a drug
Conjugation - attaching something to a drug
What is first-pass metabolism?
The first time a drug encounters the liver through the hepatic portal vein after oral administration
What can metabolism do to drug activity?
Terminate drug activity
Promote activity (Prodrugs)
- Codeine –> Morphine
- ACE inhibitors
No change
- Diazepam –> Nordiazepam
Produce toxic metabolites
- Paracetamol
