Drug-Receptor Interactions Flashcards
drug
any substance that brings about a change in biologic function (usually an increase or decrease in an existing function, rather than a new function) through it chemical actions
endogenous ligands
drugs that originate from inside the body that binds to a receptor in the body
xenobiotics
drugs that come from sources outside of the body; substance that is foreign to the body
ligand
molecule that binds to a receptor
poison
a drug with mainly harmful effects
toxin
a poison of biologic origin
receptor
a specific molecule in a biological system with which drugs interact to produce changes in the function of a system; most drugs act by binding a receptor
receptors must:
- possess an appropriate steric/chemical configuration to interact with a drug
- trigger some downstream action
target or “target receptor”
the intended receptor for a drug; the receptor that produces therapeutic effects
off-target receptor
a receptor that is not involved in the therapeutic response; may produce side-effects
specificity/promiscuity
a drug with high specificity interacts exclusively with its target; a drug that binds promiscuously interacts nonspecifically with many types of target
acceptor (or “inert receptors”)
an entity that a drug binds to, which produces no change in the function of a system
effectors
component of a system that translate the drug-receptor interaction into a change in cellular activity (an effect)
equilibrium dissociation constant (Kd)
the drug concentration at which 50% of the total receptors in the system are bound to a drug at a given time
Why do drugs differ in terms of their Kd?
because each drug has a different affinity for its receptor
Drug potency
the amount (expressed as concentration or dose) of a drug needed to produce a given level of effect
EC50 (or ED50)
Potency: the concentration or dose of drug required to produce a half-maximal effect
Drug efficacy
the largest degree of effect that a drug (or endogenous ligand) is capable of producing, if administered at the highest tolerated dose
Emax
Efficacy: the maximum degree of effect that you can achieve by increasing the drug’s concentration
agonist
a drug (or ligand) that binds to a receptor and increases the receptor’s activity (activator)
primary agonist
binds at the same site as the endogenous ligand for the receptor and produces the same type of effect
allosteric agonist/ allosteric activator
binds at a different site than where the endogenous ligand binds; alone, it produces no effect, but it changes the shape of the receptor so that when a primary agonist binds, the receptors responds with a greater than usual effect
full agonist
capable of producing the maximum receptor response
partial agonist
cannot elicit a maximum receptor response (by definition, their Emax is always lower vs. a full agonist); can be more or less potent than full agonists
antagonist/ inhibitor
a drug or ligand that reduces the effect of a receptor
competitive antagonist
binds to the same site as an agonist, but does not activate the receptor; can be overcome by adding more agonist; shifts the concentration-effect curve to the right
allosteric antagonist
binds at a site different than where the endogenous ligand binds; it changes the shape of the receptor so that when the endogenous ligand binds, the receptor responds with a lower than usual effect
irreversible antagonist
binds covalently/irreversibly to a receptor, either at the site that the endogenous ligand binds, or at an allosteric site
physiologic antagonist
acts at a different receptor to produce a physiological effect that opposes the effect of the agonist
True or False. Non-competitive inhibitors produce effects that can NOT be overcome by adding more agonist
True.
What effect do non-competitive inhibitors have on Emax?
They lower the apparant Emax of the agonist
3 non-competitive inhibitors and why they are non-competitive
allosteric, irreversible, and physiologic antagonists are all non-competitive inhibitors because they don’t compete with agonists for the same binding site
quantal dose-response curve
generated by administering many different dose sizes to a large number of subjects and recording the percent of subjects who respond to the drug at each dose
ED50
the dose that produces a therapeutic effect in 50% of the subjects (the 50% effective dose level)
TD50
50% toxic dose level. The dose that produces a toxic effect in 50% of the subjects
therapeutic window
refers to the range of doses that produce therapeutic effects, but not toxic effects in most subjects
therapeutic index
a way to express the size of the therapeutic window numerically. calculated as TI = TD50 / ED50
narrow therapeutic index drugs
those with less than a 2-fold difference between minimum effective and toxic concentrations; requires careful titration of plasma concentrations and patient monitoring
