Exam I: Pharmacodynamics

Question 1

What are the most common mechanisms for drug interactions?

Answer 1

Synergism (potentiation)

Antagonism

Altered cellular transport

Effects on receptor sites

Question 2

Why is understanding pharmacodynamics important?

Answer 2

• Provide basis for rational therapeutic use of a drug

- Design of new and superior therapeutic agents

Question 3

The four most important parameters governing drug disposition are:

Answer 3

1. Bioavailability
2. Volume of Distribution
3. Clearance
4. Elimination

Question 4

How many half-lives does it take to get to steady state? (exam purpose number)

Answer 4

5

Question 5

Define steady state

Answer 5

rate in = rate out

The amount of drug administered in a given period is equal to the amount eliminated in that same period

Question 6

How does a drug’s clearance and elimination half-life have an effect on a dosing regimen?

Answer 6

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

Question 7

1st Order Elimination: what shape is the graph?

Answer 7

Linear

Question 8

1st Order Elimination: Are drug elimination pathways typically easily or not easily saturated (maximized)?

Answer 8

NOT easily saturated (NOT easily maximized)

Elimination rate increases in DIRECT PROPORTION to serum drug concentration

Question 9

Is half-life independent or dependent of drug concentrations in 1st order elimination

Answer 9

Independent

Question 10

Does 1st order elimination hold true for IV administration?

Answer 10

Yes

Question 11

Does 1st order elimination hold true for oral drug administration?

Answer 11

No.

% absorption may decline with higher doses…it may have maximized the absorption process

Question 12

Zero-order elimination: Are drug elimination pathways easily or not easily saturated (maximized)?

Answer 12

Easily saturated (maximized)

Question 13

Zero-order elimination: Relationship between dose administered and serum drug concentration

Answer 13

Elimination rate is CONSTANT so…

Serum drug concentration is DISPROPORTIANT to the dose administered.

Small increases produce large increases in serum concentration

Question 14

Is half-life independent or dependent of drug concentrations in zero-order elimination?

Answer 14

Dependent

Question 15

Which is more dangerous?

1st Order or Zero order elimination?

Answer 15

Zero Order elimination

–> A small increase in dose can have a huge increase in serum concentration and potentially reach toxic levels

Question 16

What is the primary determinant of how long it will take for a drug regimen to reach steady-state?

Answer 16

A drug’s half life

–> The shorter the half-life, the shorter it takes to reach steady-state

Question 17

What are some factors that cause a drug-regimen to be “knocked out” of steady-state?

Answer 17

1. Frequency of dose
2. Method of administratio
3. Anything that changes absorption
4. Taking another drug
5. Liver function

**Anything that changes input or output

Question 18

What happens to drug concentration once steady-state is reached?

Answer 18

Drug concentration reaches an equilibrium

Question 19

Three types of receptor-effector systems:

Answer 19

1. Enzyme in intracellular space
2. Neurotransmitter reuptake transporters
3. Voltage-activated ion channels

Question 20

5 types of transmembrane-signaling mechanisms:

Answer 20

1. Drug diffuses into cell membrane and then to intracellular receptor
2. Drug binds to transmembrane receptor that has an outer receptor domain and an inner effector mechanism domain converting A –> B
3. Drug binds to transmembrane receptor that activates JAKs inside which phosphorylate STAT. STAT regulates transcription
4. Drug binds to transmembrane channel that is gated open or closed
5. Drug binds to transmembrane receptor (G protein-coupled receptor) that activates a separate effector molecule

Question 21

Tachyphylaxis

Answer 21

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

Question 22

Example of drug that can cause tachyphylaxis

Answer 22

Albuterol for treatment of asthma

Question 23

Down Regulation

Answer 23

Long-term reductions in receptor number which occur in response to continuous exposure to agonists

Question 24

Up Regulation

Answer 24

Increases in receptor number which occur when receptor activation is blocked for prolonged periods by pharmacologic antagonists or by denervation