Pharmacodynamics Flashcards
What are drugs?
- any substance that brings about therapeutic change
- can vary in size from very small (MW <10) to very large (MW >10,000); too large|small creates issues
Pharmacodynamic
effect the drug has on the body
Agonism
- inducer/stimulator
- mimic actions of endogenous compounds
- interacts with a receptor to produce a response
Partial Agonism
- best can do is less than agonist
- still stimulates but not as well
Inverse Agonism
- stimulate baseline level to 0
- binds to the same receptor as an agonist, but produces the OPPOSITE effect
- requires that the receptor has a basal level of activity in absence of ligand
Antagonism
- blockers: don’t stimulate anything
- no internal activity of its own; only BLOCK
Receptors determine relationship
- # receptors occupied by drug (affinity: how tightly bound)
- total # receptors there are = max level
Effect (equation)
[D] x Emax
__________
[D] + EC50
Emax: maximal effect
EC50: drug concetration that elicits half-max response (inflection curve of the S on a chart)
Potency Ratio (equation) (Potency comparison between two drugs)
EC50 Drug A
____________
EC50 Drug B
- difference in potency between two drugs
Potency Definition
EC50 Relationship
- measure of how much drug is required to elicit a response
- —- HIGH EC50=LOW potency (inverse relationship!)
Efficacy
DIRECT RELATIONSHIP TO Emax
-higher Emax = greater efficacy
EFFICACY is not POTENCY
Efficacy and Potency uses
- Efficacy = what drug/selection choice (also take into consideration drug side effects)
- Potency = dose/how much in needed
Antagonists
- block actions of endogenous agonists
- function’s “invisible”
- monitor antagonist by effect on known agonist
Competitive Antagonists
- reversible binding
- highest affinity wins
- can be overcome by adding more agonist
***Emax UNCHANGED, EC50 INCREASES (makes agonist appear less potent)
Noncompetitive Antagonists
- irreversible binding
- prevents agonist from reaching Emax
- can not be overcome by adding more agonist
***Emax REDUCED (due to the reduced number of receptors) EC50 UNCHANGED (makes agonist appear less efficacious; makes appear as partial agonist)
Spare Receptors
- when there are more receptors than needed to achieve Emax (max response)
- no different from non-spare receptors
- target max response with less drug
- ** Increase the sensitivity of the tissue toward the drug
- ——increase likelihood of a drug being bound when present at low concentrations
How are spare receptors revealed?
by using irreversible antagonists to prevent agoinst binding to a portion of receptors
- makes appear competitive because of spare receptors
- antagonist wont block all receptors to begin with; will need to increase [antagonist] and see if you get a noncompetitive response over time
Limitations of Graded Dose Response Curves
- difficult to construct when pharmacological response is an “either-or” situation
- a quantitative dose-response relationship in a single individual may have limited applicability to other individuals, due to inter-individual variability
- clinical trials Y/N: can’t measure shades of grey
Quantal Dose-Response Curve
- dose required to produce a specified response in a large number of individuals
- ** provide the median effective dose (ED50) at which 50% of the individuals exhibit the specified quantal response***
- dose in which 50% of people in the study responded
- ** provides a convenient way to compare the ED50 and TD 50 of drugs in a clinical setting
Toxic Dose
- dose required to produce a particular toxic response in 50% of people
Therapeutic Index
- margin of safety of a drug; determined in part by dose-response curve and comparing ED50 and TD50
- higher TI = better/safer
- TI below 5% difference = v. toxic drug
Therapeutic Index (equation)
TD50
_____
ED50
