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Kinetics > Exam 3 > Flashcards

Exam 3 Flashcards

1
Q

what is D?

A

dose

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2
Q

what is tau?

A

dosing interval

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3
Q

what is D/tau

A

dosing rate

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4
Q

at how many half lives does tau have to equal so that each dose behaves like a single IV bolus, complete elimination before new dose, no accumulation of the drug?

A

5 half lives or greater

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5
Q

typical clinical situation, drug accumulates in plasma (accumulation factor), Cmax and Cmin increase with each dose up to a point, steady state reached after certain time but time to reach SS depends on k (therefore half life), no further accumulation after SS (Cmax and Cmin remain constant after SS)

A

tau is less than 5 half lives

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6
Q

stable condition that does not change over time or in which change in one direction is continually balanced by change in another, accumulation does not change with each dose, Cmax and Cmin remain constant, concentration fluctuates between Cssmax and Cssmin where the goal is to keep Cssmax and Cssmin in therapeutic range

A

steady state

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7
Q

time to SS does NOT depend on……

A

dose (D) or dosing interval (tau)

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8
Q

balance between drug entering and leaving plasma, dosing rate is constant, elimination rate increases as plasma concentration increases (proportional), elimination rate eventually equals dosing rate

A

why SS is achieved with multiple dosing

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9
Q

what don’t we know at steady state?

A

peak and trough concentrations, whether or not within therapeutic range

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10
Q

compares Cmax after n doses to max concentration after first dose, depends on n, k, and tau but does NOT depend on dose, if this equals 1.0 there is NO accumulation but this also cannot be less than 1.0!

A

accumulation factor, Raccum

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11
Q

if tau increases, what happens to Raccum and why?

A

Raccum decreases because more time between doses means more elimination

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12
Q

if half life increases (k decreases), what happens to Raccum and why?

A

Raccum increases because it takes longer for the drug to be reduced by half so it accumulates more

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13
Q

at steady state, the concentration does this between Cssmax and Cssmin, depends on tau and k, does NOT depend on dose

A

fluctuation

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14
Q

what factors affect Css?

A

clearance, Vd, dose, dosing interval

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15
Q

if you increase dose but leave tau constant, what happens to Css and difference between Cssmax and min? what about fluctuation?

A

increases, no change in fluctuation

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16
Q

if tau is less than half life, what happens to fluctuation and accumulation?

A

fluctuation is smaller, accumulation is higher

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17
Q

if tau is greater than half life, what happens to fluctuation and accumulation?

A

fluctuation is greater, accumulation is lower

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18
Q

if we dose more frequently (decrease tau), need smaller or larger dose to avoid toxicity while retaining efficacy?

A

smaller

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19
Q

if we dose less frequently (increase tau), need smaller or larger dose to achieve efficacy without toxicity?

A

larger

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20
Q

for drugs with long half life, does it take longer or shorter to reach SS?

A

longer

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21
Q

high first dose to immediately reach desired SS concentration

A

loading dose, DL

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22
Q

start regimen at regular dosing intervals to maintain Css

A

maintenance dose, Dm

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23
Q

series of short IV infusions, infusion stopped before reaching SS, infusions given over regular dosing intervals (tau), compromise between multiple IV bolus and constant IV infusion (avoids high peaks of multiple IV bolus with less risk of drug related adverse effects)

A

intermittent IV infusion

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24
Q

time after first infusion is begun

A

t’

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25
Q

post infusion time equals…..?

A

tau - t’

26
Q

how do we reduce fluctuation in intermittent IV infusion?

A

make post-infusion time smaller (for example increase t’ and keep tau constant)

27
Q

time after last infusion was STOPPED

A

t*

28
Q

when is fluctuation less acceptable?

A

when drugs have a narrow therapeutic index

29
Q

nonlinearity can be due to the effect of….?

A

saturation of enzymes, disease (change in physiology), drug interactions

30
Q

elimination kinetics are not first order, elimination half life and k change with dose of drug (half life increases as dose increases), plasma concentration increases disproportionately with dose, AUC is not proportional to amount of bioavailable drug

A

nonlinear kinetics

31
Q

maximum rate of reaction in nonlinear kinetics

A

Vmax

32
Q

drug concentration at which reaction occurs at half Vmax, inversely related to enzyme affinity for drug (increased this means decreased enzyme affinity for drug)

A

Km

33
Q

as Vmax increases what happens to elimination rate?

A

increases (drug stays in body for less time)

34
Q

as Km increases what happens to elimination rate?

A

decreases (drug stays in body for more time)

35
Q

as Vmax increases what happens to AUC?

A

decreases (if elimination is faster less of the drug is bioavailable)

36
Q

dosing rate

A

R

37
Q

the initial rate of drug biotransformation increases, saturation occurs at lower Cp (toxicity at lower doses), patients with this exhibit greater changes in rate of elimination when dose is changed leading to greater adverse effects

A

decreased Km

38
Q

enzyme induction and liver disease can affect Vmax or Km?

A

Vmax

39
Q

competitive inhibitors can affect Vmax or Km?

A

Km

40
Q

as dose increases in nonlinear kinetics what happens to half life, clearance, and AUC?

A

increases, decreases, increases

41
Q

drug increases the expression of the enzymes responsible for its elimination, promotes its own destruction

A

auto-induction

42
Q

drug/metabolites inhibits the metabolism of parent drug

A

auto-inhibition

43
Q

occurs primarily via the circulatory system, mixing of drug in blood is very rapid, only a small amount of drug reaches site of action, relative distribution of drug between plasma and rest of body

A

drug distribution pattern

44
Q

amount of plasma in an average person

A

3L

45
Q

amount of extracellular fluid in an average person

A

15L

46
Q

amount of total body water in an average person

A

40L

47
Q

what is the ultimate barrier that drugs have to get through?

A

cell membranes

48
Q

do lipophilic or ionized drugs have an easier time crossing cell membranes?

A

lipophilic

49
Q

blood flow variable (blood flow to the tissue)

A

Q

50
Q

tissue volume variable (how large tissue is)

A

V

51
Q

lipid solubility, related by this variable, organ drug concentration over venous drug concentration ratio, greater this means greater ability to go to tissues

A

R

52
Q

first order distribution rate constant

A

kd

53
Q

the greater the distribution half life, the longer or shorter it takes for drug to enter and leave tissue?

A

longer

54
Q

what tissue has the longest distribution half life because it has very low blood supply?

A

fat

55
Q

for most drugs the rate of delivery from the circulation to a tissue depends on what?

A

blood flow, Q

56
Q

do highly or lowly perfused organs/tissues rapidly attain drug concentrations?

A

highly perfused

57
Q

higher logP means greater or smaller lipophilicity?

A

greater

58
Q

high Po/w means high or low lipid solubility that penetrates most membranes?

A

high

59
Q

low Po/w means high or low lipid solubility, does not penetrate BBB for decreased risk of CNS toxicity

A

low

60
Q

high Po/w means high or low R?

A

high

61
Q

in liver, heart, renal failure there is an (increased/decreased) cardiac rate and perfusion to tissues, (increased/decreased) rate of drug distribution, (increased/decreased) drug levels in tissues

A

decreased for all

Kinetics (3 decks)

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