Flashcards in ICPP - Pharmacodynamics Deck (33):
Give some examples of drug targets (RITE)
- Ion Channels
How is molarity calculated?
Molarity = g/L divided by Mr (molecular weight)
Put these in order from largest to smallest:
Nanomolar, millimolar, picomolar, micromolar, molar
Molar, millimolar, micromolar, nanomolar, picomolar
Why are drug concentrations measured in molarity rather than mg/L?
They may have a different molecular weight, so they could have the same conc in mg/L but a larger number of molecules (which determines drug action).
What is a ligand?
Molecule (or ion) that binds specifically to a receptor
What does an antagonist do?
Blocks the binding of an endogenous agonist
What is the difference between affinity and intrinsic efficacy?
Affinity governs whether something will bind to a receptor, while intrinsic efficacy governs whether it will activate the receptor.
The ability of a ligand to cause a response
Do agonists and antagonists have efficacy and intrinsic efficacy?
Agonists have intrinsic efficacy and efficacy. Antagonists have affinity only, meaning they cannot cause a response after binding to the receptor.
How are drug-receptor interactions measured?
Often by binding of radioactively labelled ligand (radioligand) to cells/membranes. Low [ligand] = low binding, high [ligand] = high binding
What is Bmax?
Like Vmax, the maximum binding capacity
What is Kd?
The concentration of ligand required to occupy 50% of the available receptors. It is an index of affinity, so low value = high affinity.
How is Kd obtained usually?
Radioligand binding, although it can also be determined by other means and is then known as KA.
Why are graphs showing proportion of bound receptors against [drug] usually sigmoidal?
Because conc of drug is so small that it is done with a logarithm, like pH.
What is the EC50?
Effective Concentration giving 50% of the maximal response. Note - on graphs where [drug] is a log, remember that the EC50 when read off the graph will also be a log.
What is the difference between concentration and dose?
Concentration is a known concentration of the drug at the site of action eg cells, while dose is the amount given to the patient (eg. in mg), meaning that the concentration at the site of action is unknown.
Why is EC50 such an effective measuring tool for potency?
It takes into account both affinity and intrinsic efficacy, and also cell/tissue specific components.
Affinity + efficacy = potency
Outline very simply the mechanism of bronchodilation in the lungs.
Adrenaline binds to B2-adrenoceptors (GCPRs) causing relaxation.
Why is it not acceptable to just target B-adrenoceptors generally when treating asthma?
There are B1-adrenoceptors in the heart, and targeting them would increase the force and rate of heart beats
What two drugs are often used to treat asthma? Outline their benefits/drawbacks.
- less selective for B2
- easier route of administration
- better efficacy when bound to B2
- short acting
- very selective for B2
- difficult to administer
- no selective efficacy
What are "spare receptors" and why do they occur?
Receptors left over even though full response has been reached, and they may occur when the response is limited by other factors eg. a muscle can only contract so much
"Amplification" may also cause spare receptors. What is "amplification"?
Also known as cascade response, seen when a few molecules of signal molecule cause a relatively massive cell response, eg adrenaline
Give a reason for having spare receptors in the lungs
Increases sensitivity, allowing responses at low concentrations of agonist
True or false - receptor numbers are fixed?
False - they can increase with low activity or decrease with high activity.
As the response increases towards 100%, what does it indicate about the intrinsic efficacy of the agonist?
It is also increasing
Give a benefit of using a partial agonist.
Can allow a more controlled response
What factor can change a partial agonist into a full agonist?
Increasing receptor number
What are the three types of antagonists?
- reversible competitive
- irreversible competitive
What is IC50?
Index of antagonist potency determined by [agonist].
How does the graph of response vs [agonist] change for a reversible competitive antagonist?
Parallel shift to right, as max response does not change, but EC50 is raised.
Why might a high affinity, competitive antagonist at opioid receptors be useful?
Reversal of opioid-mediated respiratory depression (basically an antidote to opiate overdose). Competes effectively for receptors.
What does an irreversible competitive antagonist do to a graph of response vs [agonist]?
Shifts right at first as spare receptors are filled by antagonist, then moves lower as insufficient receptors for maximal response.