Pharmacodynamics - Part 1 Flashcards
What is the definition of pharmacodynamics?
The study of the impact of drugs on the body or drug actions.
No drug produces a _______ effect.
single
Drug actions occur because _______ binds to _______ ______.
drugs - cellular targets
When drugs bind to cellular targets this:
- initiates ________ ________
- pharmacological effect is due to the alteration of an intrinsic physiological process and ___ the creation of a _____ process.
biochemical reactions
NOT - new process
Every drug tends to have more than one ______, and thus more than one _____.
target
action
In this class, the term cellular target can be used interchangeably with what?
receptor
In drug action, we cannot create ____ ________.
We can either ______ the process or ________ it.
new processes
enhance or inhibit
Drug action essentially alters what?
Intrinsic physiological processes
Where are drug targets present?
Cell surface
Organelle within the cell
In the cytoplasm
There is a _______ number of receptors in a given cell.
This means that _______-mediated responses _______ upon ________ of all receptors.
finite
receptor
plateau
saturation
What are different drug targets?
Proteins/glycoproteins
Nucleic acids
Carbohydrates
Lipids
What are the different protein/glycoprotein drug targets?
Enzymes
receptors
What are the different nucleic acid drug targets?
DNA and RNA
What are the different Carb drug targets?
Glcyogen
Cell surface receptors
What is the lipid drug target?
Cell membranes
Most receptors or drug tragets are of what kind?
Proteins/glycoproteins.
Drug action occurs:
- when the concentration or quantity of the drug at the site of responsive tissue attains a certain _______ ________ level
critical minimal
The certain critical minimal level which equates “effective” level can be determined by __ general factors?
What are they?
4
- affinity of the drug to the targets
- Ability of the drug to cause changes
- Responsiveness of the target to the changes
- adaptability of the target-tissues/organs to the changes
The 4 general factors for determinign the effective level of drug concentration for drug action:
- ______ of the drug to the targets
- Ability of the drug to cause ______
- ____________ of the target to the changes
- ___________ of the target-tissues/organs to the changes
Affinity
changes
responsiveness
adaptability
What is critical for drug action to occur?
Drug needs to be present near the receptor, and in sufficient quantity
Describe a drug that would not cause a change.
Diagnostic compound that binds to receptor to track changes but doesnt cause any change.
Describe adaptability to drug action.
Change occurs, but cell adapts to the change.
- body might produce more receptor
Why is drug adaptability important for drug action?
If the cell adjusts too quickly, drug action may not occur
The affinity of drug targets refers to:
- the ______ of binding between the drug and receptor
strength
What does the affinity of drug targets mean?
The strength of binding between the drug and receptor
The number of occupied receptors is a function of the balance between ______ and _______ drug
free and bound
What are the different intermolcular interaction important for drug affinity to a target?
Ionic, H-bond, VdW, Covalent
Describe not easily breakable covalent bonds.
Some drugs bind to targets irreversibly and remove the target from its natural action completely
- ex: tamoxiffen cancer drug
The majority of drug binding to targets is ________.
reversible
For the majority of drugs, they _______ with natural compounds for the natural _______.
compete
target
When a drug binds covalently and the bond is not easily breakable, this means?
The action is permanent
Affinity is used to describe how ______ the interaction between the ______ and the _______ is.
strong
ligand
receptor
What is the measure of drug affinity?
Dissociation constant - Kd
kd is reciprocally related to what?
ka
Using the standard A = B –> AB nomenclature, provide Kd and Ka.
ka = AB/A + B kd = A+B/AB
The association constant can be thought of as the eqb constant in the ______ direciton; the dissociation constant can be thought of the eqb constant in the ______ direction.
forward
reverse
At equilibrium, what is Kd equal to?
kd/ka = Kd
Experimentally, related to Kd, a _______ ______ can be plotted.
binding curve
What are the axes of the binding curve?
Y - fraction B bound
X - Concentration of A free
How can one determine Kd from a binding curve?
When 50% of B (receptor) is bound by A (ligand), the binding curve value is equal to Kd.
A translation to the right of the binding curve means what?
Left translation?
Right - binds worse, less affinity
Left - more affinity
What is an issue with the binding curve?
Hard to determine the 50% mark by eye-balling
What is the linear plot equivalent of a binding curve?
Scatchard plot
What are the different parts of a scatchard plot?
Y - [fraction bound B/A]
X - [Fraction bound B]
y-intercept = 1/Kd
slope = -1/Kd
Define the dissociation constant.
Measure of a drug’s affinity for a given receptor
Defined as the concentration of a drug required in solution to achieve 50% occupancy of its receptors.
A higher affinity shows ______ concentration of drug required in solution to achieve 50% occupancy of its receptors.
less
Define efficacy.
Degree to which a drug is able to produce the desired response.
Define potency
Amount of drug required to produce 50% of the maximal response the drug is capable of inducing
What is potency used for?
Compare compounds within the SAME class of drugs
What is effective concentration 50% (ED50)?
Concentration of the drug which induces a specified clinical effect in 50% of subjects
What is the Lethal dose 50% (LD50)?
concentration of the drug which induces death in 50% of subjects
What is the therapeutic index?
Measure of the safety of a drug.
- provides the margin of safety
Margin between the therapeutic and lethal doses of a drug
How is the therapeutic index calculated?
LD50/ED50
