Drug target sites Flashcards
What do drugs do?
Produce specific effects
What are the target sites drugs act on?
Receptor
What are agonists?
A drug which acts on a receptor and produces a response (increase/decrease activity of the cell)
What is an antagonist?
A drug which prevents the response of an agonist
What are drug receptor controls?
Selectivity of drug effect
Magnitude (size) of response
Mechanisms to mimic/prevent physiological function
What is a dose?
Amount of drug
What is concentration?
Amount of drug per unit volume
What are the common units of a dose?
Micrograms (ug, 10-6 grams)
Nanomoles (nmoles, 10-9 moles)
What are the common units of concentration?
Micromolar (uM, 10-6 moles per litre)
Nanomolar (nM, 10-9 moles per litre)
How does an agonist bind to its receptor?
With weak bonds
E.g. electrostatic forces, van der waals bonds and hydrogen bonds
What are the reactions between an agonist and receptor to produce an effect?
Agonist + Receptor ←→ Agonist-Receptor
[A] + [R] ←→ [AR]
[AR]→Effect
What are drug-receptor interactions?
‘Stereo-selective’
How are ligand/receptor interactions defined?
In 3 dimensions
What does the ligand/receptor interaction mean?
Display selectivity for one stereo-isomer of a ligand over another
What is the magnitude of response?
[AR] = [A]
[RT] Kd + [A]
What does [A] stand for?
Agonist concentration
What does [AR] stand for?
Agonist-receptor concentration
What does [Rt] stand for?
Total receptor concentration
What does Kd stand for?
Dissociation constant
What type of response is the magnitude of response?
Hyperbolic
What are dose-response curves?
Hyperbolic
Complex relationship between dose and response
What are log dose-response curves?
Sigmoid shape
Simple relationship between log dose and response, i.e. log-linear (between 20% and 80% maximum response)
What information can be revealed from a log dose-response curve?
Threshold dose Maximum dose Effective dose range Half-maximal effective dose ED50
What is the potency of a log dose-response curve?
Related to affinity of drug for receptor
Determines dose required for effect
ED50 is a useful index of potency
What is the efficacy of a log dose-response curve?
An index of maximum response a drug can induce, i.t. its effectiveness
What is the efficacy of full agonists?
Have high efficacy (1.0)
Produce the maximum response possible at a given receptor
What is the efficacy of partial agonists?
Have low efficacy (<1.0)
Fail to produce the maximum response possible at a given receptor
How do antagonists block agonists?
Act on the same receptor site as the agonist
Act at a different site in the pathway leading to a response
Activate an opposing physiological mechanism
Interact chemically with the agonist
What are competitive antagonists?
Antagonists which act on the same receptor site as the agonist
What do competitive antagonists do?
Have affinity for receptor
Compete with agonist molecules for the receptor
Why is there no effect when an antagonist binds to a receptor?
Antagonist has no efficacy at the receptor
The antagonist/receptor complex cannot activate transduction mechanisms and therefore there is no effect
What are the two type of competitive antagonists?
Reversible (Surmountable)
Irreversible (Insurmountable)
What kind of bonds does a competitive reversible antagonist make with the receptor?
Weak bonds
What can happen when agonist concentration is increased when a competitive reversible antagonist is attached to the receptor?
The chance of agonist molecules interacting with the receptor is increased
The effect of the antagonist can be reversed
The antagonist is competitive and reversible
In the presence of a competitive reversible antagonist the agonist log-dose response curve changes how?
Is shifted to the right
Is parallel to the curve for the agonist acting alone
Has an unchanged maximum response
What happens if the concentration of the agonist increases the reversible competitive antagonist?
The agonist overcomes the effect of the antagonist
What kind of bonds does a competitive irreversible antagonist create with the receptor?
Covalent bonds
What happens if an antagonist creates covalent bonds with the receptor?
The antagonist binds irreversibly to the receptor
Increasing the concentration of the Agonist cannot reverse the binding of the antagonist
The antagonist is competitive and irreversible
In the presence of a competitive irreversible antagonist, what does the log-dose response curve look like?
Is not parallel to the log dose-response curve for the agonist acting alone
Has a depressed maximum response
What can happen when agonist concentration is increased when a competitive irreversible antagonist is attached to the receptor?
Does not overcome the depression of the maximum response produced by a competitive irreversible antagonist
What kind of agonist log-dose response curve do some competitive irreversible antagonists produce?
Parallel shift before producing a depression in the maximum response
