Session 6: Pharmacodynamics Flashcards
What is molarity?
The concentration of moles of a substance
Why is molarity important as oppose to just giving the concentration (mg/L) of a substance?
The molarity takes into account the molecular weight and can give completely different molarity of compounds of different Mr, even when given at the same concentration
What is a ligand?
A molecule (or ion) that binds specifically to a receptor
Most drugs work in one of two ways.
What are these two ways of drug action.
1) By blocking the binding of an endogenous agonist (Antagonist)
2) By activating a receptor (Agonist)
In order to bind to a receptor, a ligand must have what for the receptor?
Affinity
The higher the affinity of a ligand for the receptor, the ________ the binding
Stronger
In order to activate a receptor, a ligand must have what towards the receptor?
Intrinsic efficacy
Binding of ligand is governed by what?
Affinity
Receptor activation is governed by what?
Intrinsic efficacy
True or false: A response is generated if there is enough intrinsic efficacy to generate one
False, other things need to happen inside the cell apart from intrinsic efficacy in order to generate a response
What is the name given to the ability of the ligand to activate the receptor AND activate cell and tissue dependent factors that are required to cause a response?
Efficacy
Do agonists have intrinsic efficacy or efficacy?
BOTH!
Do antagonists have intrinsic efficacy or efficacy?
Neither!
Do antagonists have affinity?
Yes
When an antagonist binds to a receptor, how does this prevent a response?
The antagonist binds to block the receptor, but there is no intrinsic efficacy, the receptor is not activated and the shape of the receptor is not changed, cannot activate the effector
How do we measure drug-receptor interactions by binding?
Binding of a radioactively labelled ligand (radioligand) to cells or membranes prepared from cells
When the proportion of bound receptors is plotted against the concentration of drug, what kind of curve can be seen?
Rectangular hyperbola
What is the Kd?
The dissociation constant: the concentration of drug at which 50% of AVAILABLE receptors are occupied
What is Bmax?
The maximum binding capacity receptors
The Bmax gives us information about what?
The receptor number
The Kd gives us information about what?
The affinity of the drug for the receptor
The _______ the Kd value, the higher the affinity of the drug for its receptor
Lower
Does the affinity affect how much ligand of it is needed to bind to the target to produce an affect?
Yes
High affinity= less ligand is needed to bind to the target to produce an affect
Low affinity= more ligand is needed to bind to the target to produce an affect
Drug concentration is usually plotted how to allow for more accurate measurements?
What kind of curve does this produce
On a logarithmic scale
A sigmoidal shape curve
Give two examples of what the “response” of an agonist could be
Change in a signalling pathway
Change in a cell or tissue behaviour (e.g. contraction)
In a concentration-response curve, what is EC50?
What is it a measure of?
The effective concentration giving 50% of the maximal response
It is a measure of agonist potency
What is the difference between concentration and dose?
The concentration is the known concentration of a drug at the site of action whereas with the dose, the concentration at the site of action is unknown
EC50 (Agonist potency) depends on what three things?
Affinity
Intrinsic efficacy
Cell/tissue components to generate a measurable response (including the number of receptors)
True or false: The same potency could occur with different combinations of affinity and efficacy
True
Give an example of a drug used to treat an illness that needs to infer specificity for its receptors over another
Asthma
beta2-adrenoceptors are the target as we want to relax the airways
beta1-adrenoceptors in the heart may be activated which causes problems in patients with angina as it would speed up the heart
Salbutamol is said to have selective __________ for beta2 adrenoceptors
This means what?
Efficacy
If it interacts with beta1 adrenoceptors it won’t activate them very well
If it interacts with beta2 adrenoceptors it will activate them well
Salmeterol has selective _________ for beta2 adrenoceptors
This mean what?
Affinity
It will activate each receptor equally, but is more likely to interact with beta2 adrenoceptor than beta1 adrenoceptor