Pharmacodynamics - Part 2 Flashcards
Chirality:
- A chiral molecule is a type of molecule that has a non-_________ mirror image.
superimposable
What is the feature that is most often the cause of chirality in molecules?
Presence of an asymmetric carbon atom
The first step for naming molecules is to identify _________.
stereocenters
R nomenclature means ________.
S means ________-________.
clockwise
counter-clockwise
Some drug targets/receptors have no ________ and can interact with any _______ and give a similar _______.
These are termed what?
selectivity
isomer
efficacy
Non-selective
When a receptor is non-selective, what does this mean?
The molecule’s (Drug’s) geometry is not involved in binding
Conversely, a receptor can be very selective meaning what?
It will interact with one stereoisomer better than the other(s).
Adverse effects generally occur due to what?
Non-specific binding
What are the two terms related to isomers that give rise to different biological effects.
Eutomer
Distomer
What is a eutomer?
Eutomer is the isomer with higher affinity of activity.
What is a distomer?
Isomer with lower affinity or activity
What is the eudismic ratio?
Indicates how much of the eutomer there is relative to the distomer - the higher the ratio, the greater the amount of eutomer
(Describes the difference in pharmacological activity between the two enantiomers of a drug.)
What is a racemic mixture?
When a drug is synthesized, often contains both enantiomers in a racemic mixture.
I.e. a eudismic mixture
When would a racemic mixture not be used?
When one enantiomer causes adverse effects.
Two drugs have the same concentration, one producers a greater effect than the other.
This drug is termed what?
More efficacious
Two drugs of a similar class produce biological effects, but one requires a lower dose. This drug is what?
More potent
What is used to measure efficacy?
Dose-response curve
Describe a dose response curve.
Y - %biological effect
X - [Drug] - can be log scale
dose at 50% of biological effect is ED50
Describe the relationship between efficacy and potency with the dose response curve.
Potency - x-axis translations
Efficacy - y-axis translations
A drug that undergoes a translation to the left on the dose-response curve is what?
More potent
A drug that undergoes an upwards translation on the dose-response curve is what?
More efficacious
The lower the _____, the higher the potency.
ED50
What is the equation for the therapeutic index?
TI = TD50/ED50
TI is _______.
unitless
A drug with a TI of 1 would be?
Bad
A drug with a large TI has a ______ margin of safety
higher
What are the two theoires (that we focus on) explaining the mechanisms of drug action?
Occupation theory
Rate theory
Occupation theory:
- Biological effect is elicited/initiated when the ______ occupies the _______ site.
ligand
binding
What is the occupation theory?
Biological effect is elicited/initiated when the ligand occupies the binding site.
The occupation theory states that for a drug to act, it needs to have a ______.
target
Occupation theory
- intermolecular reaction is ______ formed and ______.
readily
reversed
Occupation theory:
- the level of biological effect is proportional to what?
the number of occupied sites
According to the occupation theory, the more sites that are occupied, the _____ the biological effect that is observed.
higher
According to the occupation theory, the occupation of one receptor ______ affect the other receptor’s ability to bind other ligands.
doesn’t
A key point of the occupation theory is that drug receptors are _________ of one another.
independent
Occupation theory explains the _____ ______ _____ well.
dose response curve
Drug action and occupation theory:
- Explains the level of _____ _______
- Allow _______ _____ to be used during pre-clinical studies
- Allow ______ testing based on biochemical assays
- Allow chemists to predict and design new drugs based on the _______ ________ (target interactions)
biological effect
biochemical assays
drug
structural features
Modified occupation theory:
- The interaction of a drug and its receptor involves ____ step(s)
- The ________ of the drug and the receptor, called _______ - explained by the ___ value
- The initiation of _______ effect, called ______ or _______ ________
2
complexation
affinity
Kd
biological
efficacy
intrinsic activity
According to the occupation theory,
the lower the Kd value, the ______ the interaction.
tighter
_______ _______ (alpha) is the ability of the complex to generate the response ranging from 0 to 1 or 100%.
intrinsic activity
What is the intrinsic activity?
Ability of the complex to generate the response - ranging from 0-100%.
Occupancy theory could not explain what?
When two drugs bind to the same receptor but produce different biological effects.
The occupation theory was good at explaining what?
The lower the Kd, the lower the dosage required.
Rate theory:
- the activation of a receptor is proportional to the total ______ of _______ of the drug with its target per unit time
number
encounters
According to the rate theory, the pharmacological activity of a drug is a function of what, but not of what?
Rate of association and dissociation
NOT
the number of occupied receptors.
According to rate theory, agonists do what?
Associated and dissociate very fast
According to rate theory, antagonists do what?
Associate fast, dissociate very slow
When are the rate and occupancy theory equivalent?
At equilibrium
What can the rate theory not account for?
The characteristics of different types of compounds.
What is an agonist?
Ligand that produces the same effect as the natural compound (ex: NT) that would bind to that receptor.
What is an antagonist?
Prevents the intrinsic reaction mechanism - does not cause the cell to do something else, just prevents it from doing something.
What is a good trick for remembering dissociation and association rates for an antagonist for rate theory
Unwelcome guest
comes in easily, hard to get out
The induced-fit theory, macromolecular perturbation theory and activation-aggregation theory have what in common?
Conformational changes
