Brainscape's Knowledge GenomeTM

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


See full index

PKPD > Jusko > Flashcards

Jusko Flashcards

1
Q

Description of the time course and factors controlling drug effects on the body.

A

Pharmacodynamics.

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

Capacity Constant

A

Emax

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

Sensitivity Constant

A

EC50

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

Description of the time course and factors affecting the handling of drugs by the body.

A

Pharmacokinetics

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

What was discussed in class in regards to propranolol?

A

Racial differences are observed when dose in Chinese and whites males. Furthermore, it took much higher doses to achieve the same reduction in HR in white men as it did in Chinese males.

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

PK or PD:
~Whole Body Influence
~Zero Baseline
~Simple Determinants
~Usually Linear
~Few Assays

A

Pharmacokinetics

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

PK or PD:
~Alters specific subsystem
~Starts from steady state
~Complex controls
~Predominantly nonlinear
~Diverse measures

A

Pharmacodynamics.

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

Which phase of clinical trials is the most substantial in drug modeling?

A

Phase II–> Allows for intense PK and PD evaluation of typical patients.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

QSP

A

Quantitative and Systems Pharmacology

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

In what section of a drug label should the PK/PD data be in?

A

Section 12

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Which exposure indices are required to be shown on forest plots per the FDA?

A

Cmax and AUC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the basic tenets of pharmacodynamics?

A
  1. Capacity Limitation
  2. Turnover and Homeostasis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is capacity limitation determined by?

A

The hill function and law of mass action.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Kproduction follows ___________ kinetics.

A

Zero order

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Kloss follows ___________ kinetics

A

First Order

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

In class, what was observed with Levodopa

A

Higher doses lead to a greater reduction of symptoms, however they eventually trended back to baseline.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

In class, what was observed with Prednisolone?

A

Prednisolone binds Glucocorticoid Receptors in the nucleus. However, this process is saturable, therefore prednisolone binding follows non-linear kinetics.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is Kd?

A

The concentration of drug in serum when 50% of the receptors are bound. (half Bmax)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

A lower Kd value is associated with _____________ activity.

A

The lower the Kd value, the higher the drug activity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Per Clarks Occupancy Theory, how is Ka calculated?

A

1/Kd (Fractional Occupancy)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Per Clarks Occupancy How is Receptor Occupancy Calculated?

A

Bound Receptor/Total Receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What law does Clarks Occupancy Theory Utilize?

A

The law of mass action.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Per the law of mass action, drug occupancy of a target receptor is typically ______________.

A

Non-linear

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How can Kd be calculated using the law of mass action?

A

Kd = Koff / Kon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

In class, what was discussed about dabigatran?

A

It is a direct thrombin inhibitor, which increases aPTT, leading to anticoagulation.

aPTT time has a nonlinear relationship to dabigatran concentration.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

When C > EC50, what is the effect?

A

Emax

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

When C= EC50, what is the effect?

A

Emax/2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

When C < EC50, what is the effect

A

(Emax/EC50) * C

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

In class, what was discussed in regards to metoprolol activity in both men and women?

A

Women have a higher clearance of metoprolol than men, however, they both have the same Emax. (Meaning similar BP reduction from the same dose of metoprolol.)

Shows that differences in PK do not always translate to differences in PD.

30
Q

Which plotting data using different hill factors, the __________ will remain the same, however the shape of the curve will change.

A

EC50

31
Q

In what range will a hill curve vary depending on the hill factor?

A

From 20-80% activity.

32
Q

What does a hill factor above 1 suggest?

A

Positive Cooperativity

33
Q

What does a hill factor below 1 suggest?

A

Negative Cooperativity

34
Q

How does positive cooperativity affect a curve for receptor affinity?

A

It will narrow it and raise the peak. (this is because it increases the number of binding sites when it binds.)

35
Q

How does negative cooperativity affect a curve for receptor affinity?

A

It will widen the curve, and lower the peak. This is because the same number of binding sites are present at all concentrations.

36
Q

What is the slope of an E vs Log concentration plot?

A

m= (Emax * Hill factor) / 4

37
Q

In class, what was discussed about quinidine?

A

Although females typically have a lower plasma concentration when taking this drug, they are more sensitive to QT prolongation.

38
Q

In order to model data using the hill function we need _____.

A

Good data ranging up to nearly the Emax.

39
Q

Who was the father of PKPD?

A

Gerhard Levy

40
Q

How does dose affect the duration of effect in most cases?

A

Increases it

41
Q

How does an increase in K affect the duration of effect?

A

Decreases it.

42
Q

What did J.G. Wagner discover?

A

The equation to calculate Effect.

43
Q

In class what was discussed about enaliprilat.

A

There is a delay between the PK and the effect, due to the drug needing to be converted to its active metabolite.

44
Q

What are the three main examples of simple direct effects:

A
  1. Circulating enzyme/protein activity
  2. Circulating Cell Activity
  3. Rapid Turnover Processes
45
Q

What is Keo in the biophase model?

A

The rate constant between drug acting in plasma and at the hypothetical site of action.

46
Q

How is Fick’s Law of Diffusion utilized in the biophase model?

A

Keo is a first-order rate constant defining the drug access to target sites.

47
Q

When should the biophase model be used?

A
  1. Rapid Turnover rate of PD (EKG, EEG)
  2. Target is located in a tissues (brain or muscle)
48
Q

In lecture, why were opioid mouse trials by Dr. Gary Pollack Mentioned?

A

This study established that related effects were associated with free drug concentration in the brain. (Not the same as the plasma)

Also determined an in vitro to in vivo correlation between EC50 and Ki.

49
Q

Morphine uses ____________ model.

A

Biophase —> Effect is associated with the brain.

50
Q

What is the key point of the Free Drug Hypothesis?

A

Only free drug present in plasma is available to tissues.

51
Q

In class, what was discussed with THC?

A

There is a prolonged effect associated with increasing THC %. This results in a high, but also a dramatic increase in HR.

52
Q

The delay in effect for THC is due to _____________.

A

Hysteresis

53
Q

______ indicates how fast a drug reaches its target site.

A

Keo

54
Q

In the lecture, calcium channel blockers were described to follow what model of pharmacodynamics?

A

The slow reversible binding model.
This is why there is a significant delay in effect after plasma concentrations rise with calcium channel blockers such as benidipine.

55
Q

How was Kd used for in vivo-vitro correlation with calcium channel blockers?

A

By plotting in vivo Kd versus in vitro Kd and finding a direct relationship between the two.

56
Q

If Keo is lower, what will happen to the rate of disposition?

A

It will slow down, leading to a slow rise and decline. (opposite if higher.)

57
Q

What is the basic idea of capturing the biophase.

A

The biophase needs to be captured for drugs undergoing delayed responses. This is needed as drugs with delayed responses will show a curved graph of E vs Cp due to hysteresis.

In these cases we need to plot E vs Ce (concentration in the biophase).

58
Q

Pancuronium pharmacodynamics fit what model?

A

Slow reversible binding model.

59
Q

In Biophase PD profiles:
1. Peak effects are ___________________

  1. Smaller Keo values produce ___
  2. Recession slopes are __
  3. AUC is ___
A
  1. Delayed relative to plasma concentrations and time to peak is the same for all doses.
  2. later peaks.
  3. linear and parallel.
  4. proportional to Ln dose at higher doses.
60
Q

In class, what was discussed about Trefentanil?

A

Its effect plateaus after about 6 minutes, then rises back up to baseline. the purpose of this drug was to hopefully synthesize an opioid with a fast onset, but it was no faster than alfentanil.

61
Q

What model does Piperacillin follow?

A

The cell killing model.

62
Q

In the cell killing model Kin follows _____________- kinetics.

A

First Order

63
Q

How is Ks calculated in the cell-killing model?

A

0.693/td

64
Q

Aspirin uses which model of pharmacodynamics?

A

Turnover model with inactivation.

65
Q

Pantoprazole uses which model of pharmacodynamics?

A

Turnover model with inactivation.

66
Q

why was noberastine discussed in lecture?

A

It is a histamine blocker, however the data makes it difficult to determine what model to use for it.

67
Q

What model is used for the pharmacodynamics of warfarin?

A

IDR Type 1 (inhibits Kin)

68
Q

Which model is used for the pharmacodynamics of H-2 Antagonists?

A

IDR Type 1 (Inhibits K in)

69
Q

What model is used for diuretics?

A

IDR Type II (inhibits K out)

70
Q

What pkpd model is used for INF-alpha?

A

IDR Type III (Stimulates K in)

71
Q

What pkpd model is used for terbutaline?

A

IDR Type IV (stimulates K out)

72
Q

What pkpd model is used for benzodiapines?

A

Transduction

PKPD (7 decks)

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