Pharmacodynamics I Flashcards
What is pharmacodynamics?
Biochemical and physiological effects and mechanisms (what drugs do to the body)
What is pharmacokinetics?
Absorption, distribution, metabolism, and elimination of drugs (what the body does to drugs)
What is pharmacogenomics?
Study of the genetic variations that cause differences in drug response among individuals or populations
What is an agonists?
Bind to the receptor and initiates a response
Full or partial
What is an antagonist?
Bind to the receptor but does NOT initiate a response
(blocks)
Inhibits response to an agonist
Competitive or noncompetitive
What are allosteric activators/inhibitors?
Bind to different receptor site than agonist and alters the response to agonist
What is responsible for drug selectivity?
The receptor
Are receptors:
a) Selective or nonselective
b) Reversible or irreversible
c) Endogenous or exogenous
d) Saturable or insaturable
a) Selective
b) Reversible
c) Endogenous
d) Saturable
What determines the quantitative relationship between drug concentration?
The receptor
Do enantiomers fit into and stimulate/block the same receptors?
No
Enantiomers fit a specific receptor and stimulate or block different receptors
Do stereoisomers have the same activity levels?
No
May have more or fewer binding sites, which in turn alters activity levels
Are electrostatic interactions (ionic) reversible or irreversible?
Reversible
What are two examples of electrostatic interactions (ionic)?
Hydrogen bonding
Van der Waals forces
What is a hydrophobic interaction?
When a nonpolar region of a drug binds to a nonpolar region of the receptor
What is an example of a hydrophobic interaction?
Lipid soluble drugs (local anesthetics, anticonvulsants)
Is covalent binding reversible or irreversible?
Irreversible, very strong bond
Atoms from 2 molecules share electrons
What is an example of covalent binding?
Aspirin
Define affinity (Kd)
The ability of a drug to bind to a receptor
What is the affinity at equilibrium?
Half the receptors
are bound; half the receptors are free
Kd is a measure of
Affinity
What is the relationship between Kd and the affinity the drug has for its receptor?
The lower the Kd the higher the affinity the drug has for its receptor
Define efficacy (α)
The ability of a drug to initiate a response
100% response, α = 1
0% response, α = 0
What determines the extent of a drug effect?
The number of receptors bound
What determines the maximum effect (Emax) of a drug?
Efficacy
What has affinity and intrinsic activity?
Full agonists
α = 1
What has affinity but no intrinsic activity?
Antagonists
α = 0
What has affinity but lower intrinsic activity?
Partial agonists
0 < α < 1
The Emax is a function of
- The amount of drug
- The number of available receptors
- The ability to evoke a response (efficacy)
Are efficacy and potency related?
No
What does EC50 represent?
Drug concentration (plasma) that produces 50% of the maximal effect
What is the relationship between EC50 and drug potency?
Lower the EC50, the more potent the drug
A semi-log plot compares
log of the drug concentration (x-axis) vs. the response (y-axis)
What are 3 benefits to using a semi-log plot?
- Transforms the hyperbolic curve into a sigmoid curve
- Expands the scale at low concentrations where the response increases rapidly (therapeutic effect)
- Contracts at high concentrations where the response is not changing as quickly (toxicity)
What is a semi-log plot used for?
Used to calculate Kd and EC50 and to compare the effects of different drugs at a specific receptor
Define potency
Dose required to produce a given effect
Graded Dose-Response Curves measure
A response in an individual
A steep slope indicates
A rapid response, risky
Small therapeutic window
Define threshold dose
A dose below which there is no response
Quantal Dose-Response Curves are used to measure
The frequency with which a response will occur to a given dose within a population
“all-or-none” effect
Define therapeutic ratio
Range of doses with high efficacy and
low probability of adverse effects
How is the therapeutic ratio calculated?
Difference between LD50 and ED50
TR = LD50/ED50
Define margin of safety
Factor by which the ED99 concentration needs to be multiplied by to get the LD1 concentration
The higher the margin of safety, the safer the drug
How is the margin of safety calculated?
Margin of safety = LD1/ED99
Which drug has the greatest margin of safety, A or B?
Drug A) 10 mg/kg is effective in 99% of the population
and 100 mg/kg is toxic in 1%
Drug B) 40 mg/kg is effective in 99% and 50 mg/kg is toxic in 1% of the population
Drug A
Margin of safety = LD1/ED99
Drug A - 100/10 = 10
Drug B - 50/40 = 1.25
Drug A can be increased 10 fold without being concerned about toxicity
Drug B can only be increased by a small amount before being concerned about toxicity
