P1: How do drugs work? Flashcards
What is a drug?
A substance that affects the body and elicits a change in physiology
What is the receptor theory for drug action?
- Drugs act by binding to targets and inducing a response
- Drugs do not work until they bind to their receptors
Define agonist
- Agents that elicit a positive response
- Eg. mimic NTs
Define antagonist
- Agents that act as inhibitors
- Prevent activity of endogenous hormones, enzymes and neurones
Define partial agonist
- Agents that elicit a positive response, but not to the complete extent possible
- Used for controlling
Define the law of mass action
The rate of a chemical reaction is directly proportional to the product of the activities or concentrations of the reactants
(ROR = Conc of reactants)
What is Kd? (2)
This is the dissociation constant, which is the concentration of a drug which, at equilibrium, occupies 50% of the available receptors.
It measures the likelihood that a Drug and Receptor will dissociate, higher Kd = lower binding.
What is Ka?
Affinity constant
indicates the readiness of the drug binding to a receptor
The higher the affinity, stronger the binding
Higher Kd means _____ affinity
Lower
Higher Ka means _____ affinity
Higher
Define potency
Dose of a drug necessary to have an effect
What does a low dosage say about the potency of a drug
Lower dosage = Higher potency
Define Efficacy
The effectiveness of a drug
What is Emax
Maximum effect achievable
What are the 3 major types of receptor antagonism?
- Reversible competitive
- Irreversible competitive
- Allosteric
Describe reversible competitive antagonisms affect on the Emax and log,dose(agonist) response curve
Emax not depressed
Parallel shift to the right in the dose response curve (EC50 rises)
Describe the mechanism of irreversible competitive antagonism
Binds covalently to the receptor active sites, therefore:
- decrease total number of available receptors
- decreases maximum response achievable (Emax)
Where do allosteric antagonists bind?
Binds to a separate site on the receptor from the ligand
How do allosteric antagonists work?
- Alters conformation of receptor
- Limiting agonist binding
What does pA2 rank?
Antagonist potency
What is the EC50
This is the dose of a drug needed for a half maximal response, it is a measure of potency.
What can a Scatchard Plot be used for with drugs
These can detect drugs that can have 2 or more binding sites with different affinities
What is the therapeutic window
This is the gap in doses between therapeutic and toxic effects
What is an inverse agonist and name an example
Elicits the opposite response to the endogenous ligand e.g. naloxone for heroin overdose
How is the dissociation constant (Kd) related to the affinity constant (Ka)
1/Kd = Ka
Affinity constant is inversely proportional to the dissociation constant
What is the shape of a dose response curve with Dose(agonist) on the x-axis and Response on the y-axis
Rectangular hyperbola
What is the shape of a dose response curve with Log[Dose(agonist)] on the x-axis and Response on the y-axis
Sigmoidal curve
Give an example of a reversible, competitive antagonist
Tolazoline on alpha-adrenceptors
How does irreversible competitive antagonism affect a Log Dose [Agonist]/Response curve
Non parallel shift and depressed Emax
Occasionally parallel shifts and no depression of the maximum - spare receptors
Give an example of an irreversible competitive antagonist
Phenoxybenzamine on alpha-adrenoceptors
How does allosteric antagonism affect a Log[Dose]/Response
No change in EC50, Reduced Emax
Gives an example of a reversible and irreversible allosteric antagonist
Reversible - Memantine on NMDA receptors
Irreversible - aspirin on cyclo-oxygenase 1
What kind of drug are schild plots valid for
competitive antagonists
What is the x - intercept in a schild plot
an estimate of the antagonist equilibrium dissociation constant, pA2.
