Intro to Pharmacodynamics Flashcards
What is pharmacokinetics?
Effects of the body on drugs: absorption, distribution, metabolism, elimination.
What is pharmacodynamics?
Effects of drugs on body: drug receptors, dose response curves, mechanisms of drug actions.
Inert binding site
A component of the system that a drug binds and does not change the function.
Covalent bonds in drug interactions are:
They are irreversible.
Drug removal/receptor re-activation requires re-synthesis of the receptor or enzymatic removal of the drug.
Non-covalent bons in drug interactions are:
Reversible.
Most drugs bind to receptors this way.
Strongest to weakest non-covalent bonds (3)
Ionic bond > hydrogen bond > hydrophobic interactions
3 parameters describing the interaction of a drug w/ a receptor
Affinity
Selectivity
Intrinsic activity
Affinity
How readily and tightly the drug binds to its receptor.
What is Kd?
What is the unit for Kd?
What does a low/high Kd mean?
Equilibrium dissociation constant (describes affinity).
Drug conc. at which 50% of drug receptor binding sites are occupied w/ the drug.
Kd is expressed in molar conc. (micromoles, nanomoles, etc.).
Low -> higher affinity
High -> low affinity
How do you find Kd mathematically?
L + R -> LR
Kd = ([L][R])/[LR]
Reactants over products
How is selectivity measured?
By comparing affinities of a drug to different receptors.
What is a drug’s intrinsic activity?
The ability of a drug to change a receptor function and produce a physiological response upon binding to a receptor.
Do agonists have intrinsic activity?
Yes.
They bind to a receptor and stabilize it in a particular conformation and produce a response.
Do antagonists have intrinsic activity?
No.
They bind to the receptor but do NOT change its function. They prevent activation of the receptor in the presence of an agonist. There is no pharmacological effect in the absence of an agonist.
What are inverse agonists?
They produce an effect opposite to a full or partial agonist.
- decrease receptor signaling
- decrease response at receptors
- intrinsic activity is present and related to the inhibition of receptor function
Competitive antagonists
Compete w/ endogenous chemicals or agonist drugs for binding the receptor.
Can be outcompeted.
Irreversible antagonists
Irreversibly bind to and occlude the agonist site by forming covalent bonds.
Allosteric antagonists
Bind to a site other than the agonist site to prevent or reduce agonist binding.
What happens to EC50 and Emax in competitive antagonism?
EC50 increases
Emax does not change
What happens to EC50 and Emax in noncompetitive antagonism?
EC50 does not change
Emax decreases
Nonreceptor antagonists include:
Chemical and physiologic antagonists
Arithmetically, the dose-response curve is:
More commonly, the dose response curve is:
Hyperbolic curve
Sigmoidal curve (take the log)
What is a graded response?
Answers “how much?”
Magnitude of a response varies continuously.
Usually represents the mean value within a pop. or a single subject.
What is a quantal response?
All or none, yes or no, etc. Answers “does the response occur at all?”
Requires a pre-defined response (death, falling asleep, etc.)
Used to examine the freq. of a response within a large group.
