Pharmacodynamics Flashcards
What are the five measurements units of mole?
M - molar MM - millimolar 10-3M (0.001M) UM - micromolar 10-6M (0.000001M) NM - nanomolar 10-9M PM - picomolar - 10-12M
What is affinity?
The ability for a ligand to binding to a receptor
High affinity = strong binding
What is the difference between intrinsic efficacy and efficacy?
Intrinsic efficacy - how well a receptor is activated
Efficacy - ability to produce a measurable result
What is Kd?
The concentration of ligand required to occupy 50% of all available receptors.
Low Kd = X affinity
High
What is Bmax?
The maximum binding capacity for a receptor.
In a logarithmic scale, recording [Drug]log10M, what would be the difference between -9 and -10?
In a logarithmic scale, -9 would = 10-9 and -10 = 10-10
So -9 = 1nm
-10 = 0.1nm
The difference of ONE ZERO
What is the difference between concentration and dose?
Concentration = concentration of drug at site of action. Dose = Concentration of drug at site of unknown e.g. Patient.
What is EC?
A measure of potency - effective concentration giving 50% of maximum response.
Dependent on affinity and intrinsic efficacy.
For a ligand to have great potency what three things does it require?
1) Binding to receptor (affinity)
2) Receptor activation (intrinsic affinity)
3) Things to happen (efficacy)
What receptors do asthma therapies target? Why can they can problematic?
B2-adrenoceptors
Cause relaxation of the lungs HOWEVER can also target B1 receptors in the heart, causing angina.
How to asthma drugs such as salbutamol and salmetrol work?
Are selective.
Have a small Kd therefore greater affinity in B1 receptors, but high Kd and low affinity in B2 receptors.
What are spare receptors?
When maximal response is achieved at less than maximal receptor occupancy, some receptors are classed as ‘spare’.
Seen when receptors are catalytically active e.g. G-protein couple receptors.
What impact do spare receptors have?
They increase sensitivity and allow responses at low concentrations of agonist.
How can the number of receptors change?
Increases with low activity (up-regulation)
Decreases with high activity (down-regulation)
What’s the difference between full agonists and partial agonists?
Full agonists give maximal responses and indicate great intrinsic efficacy.
Partial agonists have low intrinsic efficacy, by bind to receptors but don’t always initiate a response.
How can partial agonists be used?
Allow a more controlled response
Can be used with full agonists as an antagonists to reduce drug effect
Can be used with low levels of ligand
What are receptors do opioids target and what effect do they have on the body?
U-opioid receptor
Pain relief, euphoria, can cause respiratory depression (hypoventilation).
How can buprenorphine be used to slowly withdraw from heroin?
Buprenorphine has a higher affinity (lower Kd) and lower efficacy than morphine.
Therefore in the presence of morphine buprenorphine becomes a antagonist against heroin but will still give some of the effects.
What are three types of antagonist?
Reversible competitive antagonists
Irreversible competitive antagonists
Non-competitive antagonists
What effect does an increased concentration of reversible competitive antagonists have agonist affinity?
Affinity increase therefore Kd decreases
What is IC50?
An index of antagonist potency.
What is irreversible competitive antagonism?
Once bound with antagonist, the receptor will never bind with anything again.
In high concentrations, there will be insufficient receptors for agonists to produce a full response.
What is a phenchromocytoma and how does the drug phenoxybenzamine help to treat it?
A phenochromocytoma is a rare tumour of the adrenal glands, causing too much adrenaline to by release, affecting blood pressure, metabolism and heart rate.
Phenoxybenzamine is a non selective irreversible competitive antagonist. Blocks the a-adrenoceptors, stopping adrenaline from raising blood pressure.
What are non-competitive antagonists and what effect can they have?
Bind to allosteric sites of receptors.
Can enhance of reduce effect of agonists.
can work in a similar way to irreversible competitive antagonists as can block receptors.
How is the the drug maraviroc used in HIV patients?
Prevents HIV from entering uninflected cells by blocking CCR5 receptors.
