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Kinetics PHRM 846 > Exam 1! > Flashcards

Exam 1! Flashcards

1
Q

Define Pharmacokinetics

A
  • what the body does to the drug

- way to measure Cp (plasma concentration vs t)

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2
Q

_______ determines the dosing interval and dosing frequency

A

pharmacokinetics

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3
Q

what are the 4 major processes that contribute to PK

A

ADME

Absorption, distribution, metabolism, elimination

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4
Q

IV push vs IV Infusion

A

IV Push/IV Bolus: one time, rapid injection into bloodstream

IV Infusion: slow “drip” into vein over set period of time to deliver a constant amount of therapy

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5
Q

IV Bolus Dose Equation for PK: is ?

A

Cp = Cp0 e^(-kt)

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6
Q

Ideas behind the one-compartment model?

A
  • well-stirred
  • fluid input and output rates are the same and constant
  • constant volume
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7
Q

one-compartment model - taking sample of liquid is like taking a sample of what in the human body?

A

blood plasma

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8
Q

After IV Bolus dose - plasma concentrations often decrease ________

A

exponentially

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9
Q

___ is the ratio of flow rate (Q) to the volume of the compartment (V)

A

k

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10
Q

how are dose, Vd and Cpo related?

A

dose = (Vd)(Cpo)

Cpo = dose/Vd

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11
Q

Vd reflects the _________ distribution of the drug

A

extravascular

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12
Q

Cp decreases more quickly when k is ______

A

large… duh elimination constant rate is large = more of the drug gone faster..

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13
Q

k is __________ of drug concentration and dose

A

independent

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14
Q

what way/equation should I use for finding k in class when given a graph/table of data? (easiest one…)

A 
linear regression line of the natural log of Cp
eq'n: ln(Cp) = ln(Cpo) - kt
(eq'n similar to y = mx + b)
m (slope) = k
intercept = Cpo
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15
Q

how many half-lives does it take for the >95% of the drug to be eliminated from the body

A

5 half-lives!

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16
Q

For a one-compartment model with IV bolus dosing - the elimination rate constant (k) is ______ proportional related to the half-life

A

INVERSELY (duh - b/c k = 0.693/half life)

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17
Q

if Vd gets smaller (and clearance stays the same) - how are k and 1/2 life affected

A

bigger k; smaller half life

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18
Q

what are the two main clearance (CL) equations to know (hint they are really simple equations…)

A 
CL = (k)(Vd)
CL = (Dose/AUC)
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19
Q

Protein Binding:

Free (or Unbound drug!) are able to do “3 special things” that bound drugs can’t do…. what are those 3 activities

A

free drugs CAN:

  • exit capillaries to reach extravascular sites of action
  • be filtered by kidney
  • be metabolized by liver
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20
Q

can drug bound to protein cross the capillary wall?

A

NOPE!

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21
Q

what are the 3 major proteins that bind to drugs

A

albumin; a1-acid glycoprotein; lipoproteins

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22
Q

why don’t we worry about the binding rates for protein binding to drugs?

A

rate of binding/unbinding is SOO fast - don’t worry about it;

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23
Q

what is the fraction unbound (fu) equation

A

free drug/total drug

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24
Q

what kind of drugs does albumin bind to?

A

weakly acidic drugs, hormones, free fatty acids

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25
Q

which protein (for protein binding) is the most abundant plasma protein

A

albumin

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26
Q

a1-acid glycoprotein aka ________ aka ______

A

AAG; orosomucoid

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27
Q

a1-acid glycoprotein primarily binds to what kind of drugs?

A

weakly basic drugs

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28
Q

what notable disease states will affect albumin levels

A

liver and kidney

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29
Q

what notable disease states will affect a1-acid glycoprotein levels

A
  • pregnancy
  • burns
  • HIV
30
Q

Lipoprotein examples

A

HDL and LDL…

31
Q

what kind of drugs does lipoprotein bind to?

A

lipophillic/hydrophobic ones, duh

32
Q

what disease states may affect lipoproteins

A

heart disease

33
Q

what are the metabolic process phases in the Liver

A

Phase 1 and 2

34
Q

what metabolic process occur in phase 1 in the liver

A

oxidation; reduction; cyclization; CYPs

35
Q

what metabolic process occur in phase 2 in the liver

A

glucuronidation; acetylation; conjugation

36
Q

for most drugs, the _____ is the major site of metabolism

A

LIVER

37
Q

blood goes back to the heart from the liver via _______

A

inferior vena cava

38
Q

2 main blood supplies of the liver

A

portal vein and hepatic artery

39
Q

portal vein brings blood to liver from

A

spleen, pancrease, intestines

40
Q

blood supplies to the liver - difference in content for portal vein or hepatic artery

A

portal - nutrient rich/O2 poor

hepatic - O2 rich/ nutrient poor

41
Q

what is the functional unit of the liver

A

lobule

42
Q

E = Hepatic extraction ratio - what is the definition of E?

A

E is the amount of drug that entered the liver but was removed by metabolism

43
Q

what are the units for E? (hepatic extraction ratio)

A

there are none!

44
Q

Clearance of Liver - is related to E (hepatic extraction ratio) how?

A

Cl(h) = Q x E

45
Q

High E Drugs - what effects it most? Q, Cl(h), E?

A

Q - blood flow (bc/ Cl(int) and f(u) soooo large that they are excluded from the Cl(h) equation) aka rate limiting step controls it all

46
Q

Low E Drugs - what effects it most? Q, Cl(int), f(u)?

A

Cl(int), f(u); (bc/ Q soooo large that it is excluded from the Cl(h) equation) aka rate limiting step controls it all

47
Q

What is the normal hepatic blood flow value?

A

1500 ml/min

48
Q

High E drug example in class

A

Lidocaine

49
Q

when given orally, _____ E drugs have a high hepatic first-pass effect and low oral bioavailability (F)

A

high

50
Q

Low E drug example in class

A

Phenytoin

51
Q

4 main renal processes of elimination

A

1 - glomerular filtration
2 - tubular secretion
3 - tubular reabsorption
4 - urinary excretion

52
Q

is the processes passive, active, or both?

Glomerular filtration

A

passive

53
Q

is the processes passive, active, or both?

tubular secretion

A

both

54
Q

is the processes passive, active, or both?

tubular reabsorption

A

both

55
Q

is the processes passive, active, or both?

urinary excretion

A

passive

56
Q

Glomerular filtration Rate (GFR) is typically about ________ mL/min

A

120-125

57
Q

Glomerular Filtration: uni- or bi- directional

A

Uni!

58
Q

Glomerular Filtration:

can ionized drugs be filtered?

A

yes

59
Q

Glomerular Filtration:

can unionized drugs be filtered?

A

yes

60
Q

Glomerular Filtration:

mostly (small or large) molecules can be filtered (approx size?)

A

small! < 500 Da

61
Q

Glomerular Filtration:

can protein bound drugs be filtered?

A

no!

62
Q

Glomerular Filtration:

can protein drugs be filtered?

A

no

63
Q

Ionization state of drug in renal tubule is determined on what two things?

A

Urine pH; Drug pKa

64
Q

Passive reabsorption of a drug in renal system is more likely to happen if the drug is _______

A

unionized

65
Q

Arterial blood flow rate to kidney is _____ mL/min

A

1000

66
Q

Typical urine flow rate?

A

1 mL/min

67
Q

If the renal clearance is < 125 mL/min….what does that be about net tubular action?

A

low number = low clearance = more (net) REABSORPTION!

68
Q

If the renal clearance is > 125 mL/min….what does that be about net tubular action?

A

high number = high clearance = more (net) SECRETION

69
Q

how is the lithium’s renal clearance interesting? (has a pretty low clearance rate - why?)

A

it is charged - like sodium - it gets reabsorbed in the renal tubule (like sodium gets reabsorbed)

70
Q

If a drug is REabsorbed renally - how does that affect half life

A

increases it (duh)

71
Q

why does metformin have such a large clearance? (talking about renally)

A

a lot of metformin gets secreted to the renal tubule and none of it gets reabsorbed…

72
Q

If a drug is metabolized by the liver and has a clearance value close to 1500 mL/min (aka close to the blood flow the liver) the drug is (low or high E)?

A

high E!

Kinetics PHRM 846 (2 decks)

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