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Kinetics - Test 2 > One Compartment Model > Flashcards

One Compartment Model Flashcards

1
Q

What is the goal of pharmacokinetics?

A

Quantitative account for the amount of drug entering and leaving the body

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2
Q

What is clinical pharmacokinetics?

A

Application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual px

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3
Q

Where is the ideal spot to take a drug sample? What is the problem with this? Where do you take a sample instead?

A
  • Ideal spot = drug in tissue b/c that’s where receptors are (so will tell you how much free drug there is)
  • Can’t take a biopsy of tissue just to see drug concentration
  • Take sample of drug in blood instead
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4
Q

What is the relationship between [drug] in plasma and [drug] in tissue? When will this relationship not occur?

A
  • Direct relationship, high [drug] in plasma (as free form) means high [drug] in tissue
  • This relationship will not occur if there is an active metabolite or if tissue is concentrating the drug
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5
Q

Why is a log dose curve sigmoidal shaped?

A
  • Each drug has a therapeutic window, in which effect will increase relative to dose increase
  • Top is flat b/c receptors become saturated, so there is no more response or the organism has died from toxicity (overdose)
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6
Q

Will the same dose of a drug produce the same peak plasma [drug]?

A

No, one dose can produce a high variability in [drug]

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7
Q

What are the components of therapeutic drug monitoring?

A
  • Assay of [drug] plasma

- Interpretation and application

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8
Q

Which drugs are commonly monitored?

A
  • Aminoglycosides
  • Antidepressants
  • Cyclosporin
  • Methotrexate
  • Valproic acid
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9
Q

When is therapeutic drug monitoring valuable?

A
  • Good correlation exists for response vs [drug]
  • Wide intersubject variation
  • Narrow therapeutic index
  • Desired effect cannot otherwise be assessed
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10
Q

When is therapeutic drug monitoring not appropriate?

A
  • No defined therapeutic [drug]
  • Active metabolite
  • Toxic reactions may occur at all [drug]
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11
Q

What is assumed w/ the one compartment model?

A

Instantaneous distribution to whole body

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12
Q

What is the two compartment model?

A
  • Immediately after administration drug circulates to highly perfused areas
  • After distributive eq’m drug reaches whole body (low perfused areas)
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13
Q

What is considered the central compartment?

A
  • Heart
  • Liver
  • Lungs
  • Kidney
  • Blood
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14
Q

What is considered the peripheral compartment?

A
  • Fat tissue
  • Muscle tissue
  • Cerebrospinal fluid
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15
Q

What is the difference between an IV bolus and IV infusion?

A
  • Bolus = administered through a needle, taking a few minutes to administer
  • Infusion = drug is diluted in an infusion bag and is slowly administered, usually taking longer than a few minutes
  • W/ bolus, Cmax occurs directly after administration; w/ infusion, [drug] slowly builds up
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16
Q

Can the same drug have a different k value?

A

No

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17
Q

Can 2 different drugs have the same k values?

A

No

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18
Q

What is the initial equation of the one compartment model?

A

dCb/dt = -KCb

- Cb = concentration in blood

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19
Q

What happens if data for a one compartment model is curved on a log scale?

A
  • Can’t do linear regression b/c will be wrong

- Those data aren’t a one compartment model

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20
Q

What is the formula to find t1/2 from k for first order?

A

t1/2 = 0.693/k

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21
Q

What is the formula to find t1/2 from zero-order?

A

t1/2 = 0.5Db/ko

22
Q

What is the formula for Vd using the one compartment open model?

A

Vd = dose/Cpo

23
Q

What is the formula for Vd using the model-independent approach?

A

Vd = dose/K * [AUC]o infinity

24
Q

What is the Vd of nortriptyline?

A

1200 L

25
Q

What is the Vd of digoxin?

A

600 L

26
Q

What is the Vd of propranolol?

A

250 L

27
Q

What is the Vd of lidocaine?

A

125 L

28
Q

What is the Vd of phenytoin?

A

40 L

29
Q

What is the Vd of theophylline?

A

30 L

30
Q

What is the Vd of gentamicin?

A

18 L

31
Q

What is the Vd of cefazolin?

A

8 L

32
Q

What is the lowest possible Vd of a drug?

A

Only distributing to the plasma fluid, which makes up 4% of body weight

33
Q

What will the [drug] vs time curve look like for an IV dose?

A

Time 0 will be 100% [drug] and will decrease from there in a curved line

34
Q

What will the [drug] vs time curve look like for an oral dose?

A

Time 0 will be 0% [drug] and will increase to a peak and then decrease

35
Q

What will the log[drug] vs time curve look like?

A

Straight line, w/ time 0 being the Cmax

36
Q

What is the formula to find K from slope? What is the special rule for this?

A

slope = -K/2.303

- This formula only works for log[drug] vs time (post absorption)W curves

37
Q

What is the difference between the absorption phase and the elimination phase?

A
  • Absorption phase = portion of a [drug] vs time curve that is before Cmax
  • Elimination phase = portion of a [drug] vs time curve that is after Cmax
38
Q

How do you determine the AUC to infinity?

A

Last [drug] value multiplied by K, then add this value to the total AUC

39
Q

Can a protein bound drug bind to a receptor?

A

No, it must dissociate into the free form to get to the receptor

40
Q

What should be done for a drug w/ a narrow therapeutic index?

A

Should be monitored w/ blood samples to see where the [drug] is and make sure it is in the therapeutic window

41
Q

What is critical to know about assays?

A

Want to do a specific assay so we know what info we’re getting and what we’re assaying (protein-bound, total, free, etc.)

42
Q

What do we care about w/ respect to the 2 compartment model?

A

The eq’m between the 2 compartments

43
Q

What is K the sum of?

A

All the different types of elimination (excretion, metabolism, etc.)

44
Q

What should be done in an emergency when you need drug levels to go up immediately?

A

Give a bolus and then follow up w/ an infusion to keep blood concentration steady

45
Q

What assumption is being made when using the rate expression (dCb/dt = -kCb)? What should be done if the drug has a narrow therapeutic index?

A
  • Assuming the px is in the 95% confidence interval
  • If they are an outlier, then the calculation would be wrong and the dose would be wrong
  • If the drug has a narrow TI, make sure the px is in the 95% interval
46
Q

What is ko?

A

The zero-order elimination rate constant

47
Q

When will Vd change?

A

If disease state changes

48
Q

When plotting a graph on log paper, do you plot the actual drug concentration or the log of the drug concentration?

A

Actual concentration

49
Q

How do you calculate AUC for 2 data points?

A

((2nd time point - 1st time point)/2) * (1st [ ] point + 2nd [ ] point)

50
Q

What is relative availability?

A

AUCa(drug product) / AUCb (recognized standard)

- If a and b are different doses = (AUCa/dose a)/(AUCb/dose b)

Kinetics - Test 2 (7 decks)

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