lecture 2 - intro to pharmacodynamics Flashcards
What are the 4 proteins types that act as sites of drug action?
receptors, enzymes, transporters/carrier molecules, ion channels
What are the most common protein drug target?
Receptors
What are the 4 types of receptors?
Ligand-gated ion channels, G-protein couple receptors, kinase-linked receptors, nuclear receptors
What is drug affinity?
The tendency of a drug to bind to a receptor/protein
What is the relative affinity of drug which bind at low concentration?
High affinity
How is affinity numerically defined?
The concentration of drug required to occupy 50% of receptors - AKA the Kd (dissociation constant)
What is drug potency?
A measure of drug activity expressed in terms of the amount of drug required to produce an effect of given intensity.
How is potency measured?
EC50 - the effective concentration of an agonist required to product 50% of the maximal drug response.
What is the relative potency of a drug with a low EC50 value?
High potency - low concentration required to reach 50% of maximal response.
What is drug efficacy?
The ability of a drug to bind to a receptor and cause a change in receptor action.
How is efficacy measured?
Emax - the maximal effect
What class of drug has positive efficacy?
agonist
What class of drug has negative efficacy?
inverse agonist
What class of drug has no efficacy?
antagonist
What are drug agonists?
drugs with positive efficacy that will activate a receptor to promote cellular response
What are drug inverse agonists?
drugs with negative efficacy that will bind to receptors to decrease basal receptor activity
What are drug antagonists?
A drug with no efficacy that will bind to receptors but have no effect on activity - thereby preventing native ligands from binding.
What are full agonists?
Drugs that elicit the maximum tissue response
What are partial agonists?
Drugs tat produce less than the maximum tissue response.
Which type of agonist will produce a maximal response at 100% receptor occupancy?
Full agonists
What is reversible competitive antagonism?
When a drug binds to a receptor in a reversible manner to compete directly with agonist binding
What shift is observed in a concentration response curve when a reversible competitive antagonist is used?
Rightward - more agonist must be added to reach maximum response
What type of bonding is used in reversible competitive antagonism?
non-covalent
What is irreversible competitive antagonism?
Drug binds covalently to receptor’s orthosteric site, reducing the number of receptors available to agonist permanently.
What is the site of a receptor where endogenous agonists bind?
Orthosteric binding site
What is constitutive activity of a receptor?
When a receptor has activity despite not having an agonist bound.
How do inverse agonists alter constitutive activity?
The prevent it - turn receptor off. useful in preventing over activity of a receptor
What is allosteric binding?
The binding of an agonist to a site other than the orthosteric binding site (where endogenous ligands bind). This results in an increase or decrease in the affinity or efficacy of the orthosteric ligand.
What are the non-receptor mechanisms of drug antagonism?
chemical, pharmacokinetic, interrupt receptor response, physiological
What is chemical antagonism?
When two substances combine in solution to prevent an action occurring.
What is pharmacokinetic antagonism?
When the concentration of a drug at the active site is reduced .
What is interrupt receptor-response antagonism?
When sites downstream of a receptor are blocked, preventing downstream effects of receptor activation.
What is physiological antagonism?
When two drugs with opposing action “cancel each out”
What are the 2 types of ion channel?
Ligand gated, voltage gated
How does blocking Na+ channels prevent pain?
Blocking voltage gated Na+ channels prevent pain signals from being transducted in neurons.
What is the effect of blocking Ca2+ voltage gated channels on neurotransmitter release?
Stops the release of neurotransmitter in neurons
What are the 2 types of enzyme inhibition?
Non-competitive, competitive
