Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

FOM - WLB > Week 4 Nordgren - Principles of Pharmacodynamics > Flashcards

Week 4 Nordgren - Principles of Pharmacodynamics Flashcards

1
Q

What is the basic definition of Pharmacology?

A

The study of substances (“drugs”) that interact with living systems through chemical processes.

(deals with both the beneficial & adverse effects)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How does Toxicology relate to Pharmacology?

A

Toxicology is viewed as a branch of pharmacology which deals with adverse effects on living systems.

“science of poisons”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is a drug receptor?

A

A cellular macromolecule that interacts with a drug and in doing so initiates a series of biochemical events that result in the characteristic action of the drug.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the functions of the receptor?

A
  • Recognition
    • the receptor binds a drug or endogenous ligand
  • Signal transduction
    • transfer of information
    • recognition of the drug needs to be communicated to the cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What does the term “selectivity” mean in the context of drug-receptor interactions?

A

The drug binds to one receptor or a small number of receptor types.

The tissue localization of different receptor types imparts specificity of drug action.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Why is the drug-receptor interaction based on selectivity and specificity?

A

It would not be helpful if a drug bount to all receptors.

The drug is intended to exert a distinctive influence on the body.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is receptor-mediated signal transduction?

A

The interaction of a drug with its receptor propagates a signal, i.e. it converts the “drug signal” into a tissue response.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the three ways transduction propagates a signal?

A
  1. Alters receptor function
  2. Generates a second messenger
  3. Impacts gene transcription
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What were the four transduction mechanisms discussed in class?

A
  1. G-protein coupled receptor signal
  2. Ligand-Gated ion channel
  3. Receptors as enzymes
  4. Receptors regulating nuclear transcription
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What do G-protein coupled receptors (GPCRs) do?

A
  • regulate second messengers
    • cAMP, cGMP, Ca2+, DAG, IP3,
  • most common drug receptor group
  • specific subunits dissociate and have their own characteristic actions
    • ex. up/down regulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the mechanism of Ligand-Gated Ion Channels?

A
  • Ligand binds → channel opens → ions flow through and down electrochemical gradient
    • drugs will interact with this channels
    • cationic & anionic
    • can lead to depolarization of the cell membrane
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How do “receptors as enzymes” work?

A
  • Intrinsic enzyme activity phosphorylates diverse effector proteins.
    • phosphorylation proteins (kinases) at specific AA residues
    • Cleave phosphate off (phosphatases)
  • lots of receptors possess enzymatic activity
  • can be inactivated or activated by ligand binding
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How do “receptors regulating nuclear transcription” work?

A
  • Receptors have the ability to bind directly to DNA
  • Regulate expression of adjacent genes
  • Often associate with a chaperone protein
    • when receptor bound by ligand, will inactivate the chaperone
  • Examples: sense steroids, thyroid hormones, etc.
    • control development, homeostasis, & metabolism
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the five major attributes of drug receptor-mediated processes?

A
  1. Highly compartmentalized
  2. Self-limiting on relatively short time scales
  3. Organized into opposing systems
  4. Provide opportunities for signal amplification
  5. Operate through a relatively small number of second messenger systems
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What two attributes of drug receptor-mediated processes contribute to drug-drug interactions?

A
  • Receptor-based processes tend to be organized into opposing systems.
  • A large number of different receptors may operate through a much smaller number of secondary messenger systems.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the non-receptor modes of drug action discussed in class?

A
  • Drugs interacting chemically with small molecules
    • EDTA, dimercaprol
  • Drugs producing physicochemical effects
    • Mannitol, MgSO4
  • Drugs that target rapidly dividing cells
    • chemotherapeutic agents, cell cycle specific drugs, and cell cycle non-specific drugs that act on dividing cells
17
Q

What are the two underlying assumptions of the Occupancy Theory?

A
  1. Effect is proportional to receptor occupancy
  2. Interaction is monovalent
18
Q

What is EC50?

A

The concentration of drug producing 50% of the maximal response and is an estimate of the drug’s KD.

19
Q

What is ED50?

A

The dose of the drug producing 50% of the maximal response.

20
Q

What does affinity mean??

A

The ability of a drug to form a complex with a receptor.

  • The greater the affinity, the lower the drug concentration required to produce an effect and occupy the receptor.
    • small KDand EC50
  • 1/KD
21
Q

What is potentcy as it pertains to drugs?

A

A comparative term used to describe the relative positions of several agonist dose-response curves.

  • High potency does NOT confer on a drug any inherent benefit.
22
Q

What is efficacy as it pertains to drugs?

A

Capacity to produce a response.

(a. k.a. Intrinsic Activity)
* Response induced by the interaction of a drug and receptor is a function of BOTH the affinity of the drug for the receptor and the efficacy of the drug-receptor complex to produce a response.

23
Q

What is a full antagonist drug?

A

A drug capable of inducing a maximum response.

(alpha = 1)

24
Q

What is a partial agonist?

A

A drug whose maximal response is only a fraction of the maximum that can be elicited.

(0 < alpha < 1)

25
Q

What is a “pure” antagonist?

A

A drug that can bind to a receptor (has affinity for the receptor), but induces no response.

i.e. zero efficacy (alpha = 0)

26
Q

What are the effects of a competitive antagonist on the dose-response graph?

A
  • Shifts to the right
  • apparent affinity of agonist is reduced
  • slope does not change
  • maximal response can still be produced
  • REVERSIBLE
27
Q

What are the effects of a non-competitive antagonist on the dose-response curve?

A
  • Slope reduced
  • apparent affinity changes very little, if at all
  • apparent numbers of receptors decreased
  • maximal response reduced
  • IRREVERSIBLE
28
Q

What are physiological mechanisms of drug antagonism?

A

Distinct from the type of antagonism described before, as it involves interaction between regulatory pathways mediated by different receptors.

  • does not involve binding to the same receptor
  • counteract an effect by using a different pathway
  • ex. insulin vs. glucocorticoids
29
Q

What is an inverse agonist?

A
  • A drug that preferentially binds to the inactive form, shifting equilibrium to the inactive form.
  • This results in an effect the opposite of that produced by an agonist.
30
Q

Describe the two-state theory of drug-receptor interactions.

A
  • Postulates that the receptor exists in an active and inactive form.
  • An equilibrium exists between these forms which results in a basal or “constitutive” level of activity in the absence of the drug.
31
Q

What are spare receptors?

A
  • A system behaves as if it has “spare” receptors
    • more than it needs
    • different EC50and KDvalues
    • violation of simple occupancy theory
    • may involve amplification and persistence of the original binding signal
    • possible that limitations on the response to receptor occupancy exist “downstream” of the ligand-receptor interaction itself
32
Q

Describe the Quantal Dose Effect.

A
  • All or None
  • quantal dose-effect curve is a frequency distribution curve of the population response to a drug
33
Q

What information do/don’t quantal log dose-response curves provide?

A
  • Do:
    • Median effective dose (ED50) - the dose required to produce the response in 50% of the population.
    • provides information on variability in the response of a population
    • can be used to judge a drug’s potency relative to that of another drug
  • Don’t:
    • provide info on a drug’s KD value or maximum efficacy
34
Q

What is the therapeutic index (TI) of a drug?

A

The ratio of the median lethal dose to the ED50

  • a measure of relative safety of a drug
35
Q

What is the Certain Safety Factor of a drug?

A

The ratio of the dose producing death in 1% of the population (LD1) to the dose of drug producing the therapeutic response in 99% of the population (ED99).

36
Q
A

FOM - WLB (20 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions