Exam I: Pharmacodynamics Flashcards
What are the most common mechanisms for drug interactions?
Synergism (potentiation)
Antagonism
Altered cellular transport
Effects on receptor sites
Why is understanding pharmacodynamics important?
- Provide basis for rational therapeutic use of a drug
- Design of new and superior therapeutic agents
The four most important parameters governing drug disposition are:
- Bioavailability
- Volume of Distribution
- Clearance
- Elimination
How many half-lives does it take to get to steady state? (exam purpose number)
5
Define steady state
rate in = rate out
The amount of drug administered in a given period is equal to the amount eliminated in that same period
How does a drug’s clearance and elimination half-life have an effect on a dosing regimen?
Drugs w/ a faster elimination rate have a decreased half life.
Decreased (or smaller) half-lives need more frequent doses
In short:
DEC. clearance and half life = INC. frequency of doses
1st Order Elimination: what shape is the graph?
Linear
1st Order Elimination: Are drug elimination pathways typically easily or not easily saturated (maximized)?
NOT easily saturated (NOT easily maximized)
Elimination rate increases in DIRECT PROPORTION to serum drug concentration
Is half-life independent or dependent of drug concentrations in 1st order elimination
Independent
Does 1st order elimination hold true for IV administration?
Yes
Does 1st order elimination hold true for oral drug administration?
No.
% absorption may decline with higher doses…it may have maximized the absorption process
Zero-order elimination: Are drug elimination pathways easily or not easily saturated (maximized)?
Easily saturated (maximized)
Zero-order elimination: Relationship between dose administered and serum drug concentration
Elimination rate is CONSTANT so…
Serum drug concentration is DISPROPORTIANT to the dose administered.
Small increases produce large increases in serum concentration
Is half-life independent or dependent of drug concentrations in zero-order elimination?
Dependent
Which is more dangerous?
1st Order or Zero order elimination?
Zero Order elimination
–> A small increase in dose can have a huge increase in serum concentration and potentially reach toxic levels
What is the primary determinant of how long it will take for a drug regimen to reach steady-state?
A drug’s half life
–> The shorter the half-life, the shorter it takes to reach steady-state
What are some factors that cause a drug-regimen to be “knocked out” of steady-state?
- Frequency of dose
- Method of administratio
- Anything that changes absorption
- Taking another drug
- Liver function
**Anything that changes input or output
What happens to drug concentration once steady-state is reached?
Drug concentration reaches an equilibrium
Three types of receptor-effector systems:
- Enzyme in intracellular space
- Neurotransmitter reuptake transporters
- Voltage-activated ion channels
5 types of transmembrane-signaling mechanisms:
- Drug diffuses into cell membrane and then to intracellular receptor
- Drug binds to transmembrane receptor that has an outer receptor domain and an inner effector mechanism domain converting A –> B
- Drug binds to transmembrane receptor that activates JAKs inside which phosphorylate STAT. STAT regulates transcription
- Drug binds to transmembrane channel that is gated open or closed
- Drug binds to transmembrane receptor (G protein-coupled receptor) that activates a separate effector molecule
Tachyphylaxis
A sudden decrease in response to a drug that occurs usually from frequent or continuous exposure to agonists resulting in short-term reduction of receptor response
Example of drug that can cause tachyphylaxis
Albuterol for treatment of asthma
Down Regulation
Long-term reductions in receptor number which occur in response to continuous exposure to agonists
Up Regulation
Increases in receptor number which occur when receptor activation is blocked for prolonged periods by pharmacologic antagonists or by denervation
