Pharmacokinetics Flashcards
What is pharmacokinetics?
the study of how an organism affects a drug
Provides a mathematical basis for the description and
prediction of the time course of drugs (and their metabolites) in the body.
What is pharmacodynamics?
the study of how the drug affects the organism
Pharmacokinetics refers to the quantitative study of ADME. What does this stand for?
ABSORPTION
DISTRIBUTION
METABOLISM
ELIMINATION
Define absorption.
All processes from the site of administration (anything non-intravenous) to the site of measurement (typically blood)
Define distribution.
The reversible transfer of drug between the site of measurement and other sites within the body.
Define metabolism.
The irreversible loss of drug from the body by biochemical conversion
Define elimination.
The irreversible loss of drug from the site of measurement within the body.
Define excretion.
The irreversible loss of drug from the body
Define disposition.
Elimination + distribution
What do the following stand for... AUC Cmax Tmax MTC MEC?
area under the curve max concentration time to max concentration minimal toxic concentration minimal effective concentration
Drugs must move across hydrophobic diffusion barriers - how? (2)
Diffusion
Carrier-mediated transport
Where are the majority of drugs absorbed from?
What is key here? (2)
GI tract
solubility (dissolution) and ionisation
What is solubility dependent on?
What is solubility a major determinant of?
The properties of the tablet i.e. surface area, drug concentration, thickness
Drug plasma levels
How do large insoluble molecules (e.g. glucose and proteins) move through the plasma membrane?
Carrier-mediated transport - they require a carrier molecule
Give some examples of carrier molecules. (4)
Ion channels, ABC transporters, water channels, ATP pumps, etc…
What is facilitated diffusion?
How does it differ for water-soluble and lipid soluble agents?
A passive process where solute moves down a concentration or charge gradient
Water-soluble agents use aqueous pores in the membrane, while lipid soluble agents diffuse through the membrane
What is active transport?
the movement of solute against a concentration (or other) gradient
utilises energy directly
Cell membranes are generally only permeable to…?
Why?
uncharged solutes
hydrophobic fatty acids repel charged molecules
What equation determines the proportion of a substance that is ionised at a given pH?
Henderson-Hasselbach equation
pH = pKa + log (A-/Ha)
If pH < pKa, what does this mean?
The non-ionised form of an acid dominates.
In the acidic stomach (pH 1.5 - 3.5), weak acids are present in what form - ionised or non-ionised?
Non-ionised
What can impair absorption of weak acids? (4)
– Gastric pH is elevated by drugs (i.e. PPIs, H2 antagonists, antacids)
– Gastric pH is physiologically higher in neonates as their gastric secretions are relatively achlorhydric (pH 6-8)
– Gastric resections (primarily for cancer) remove acidic
environment
– Modified delivery systems reduce solubility in the stomach and thus increase delivery to intestines (pH >6)
Solubility and diffusion - which favours ionised/non-ionised?
Solubility favours ionised species, diffusion favours nonionised
What factors affect gastrointestinal absorption? (4)
- pH
- Blood flow to stomach/intestine
- Gastrointestinal tract transit time
- Gastric contents
Most drugs are either ____ acids or _____bases (weak/strong).
WEAK
Clopidogrel and omeprazole - what is the interaction?
What is therefore recommended?
omeprazole added to clopidogrel therapy reduces the inhibition of platelet aggregation
Concomitant use of clopidogrel and omeprazole or esomeprazole is to be discouraged unless considered essential. Consider PPIs other than omeprazole or esomeprazole, or other gastrointestinal therapy such as H2 blockers (except cimetidine) or antacids
Why do antacids have multiple interactions?
How many this be avoided?
Can interfere with absorption of other drugs, e.g. by forming insoluble chelate complexes
Typically suggests taking 1-2 hours apart from other medications
What is p-glycoprotein?
Where is it extensively expressed?
ATP-dependent efflux pump with broad substrate
specificity.
Intestinal epithelium, liver, proximal tubule and blood brain barrier.