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Physiology Part 2 > Lec51_51 PK Clinical > Flashcards

Lec51_51 PK Clinical Flashcards

1
Q

What type of process is C vs t?

A

first order = exponential decay

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2
Q

How can you get linear C vs t graph?

A

graph log C vs t

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3
Q

How do you determine t 1/2 from log C vs t graph?

A

Choose any two concentrations that differ by multiple of 2 –> time separating each multiple of 2 is t 1/2

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4
Q

What can you say of two drugs if they have same slope in log C vs t graph?

A

they have same t 1/2

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5
Q

Does higher or lower slope mean bigger t 1/2?

A

shallower slope = bigger t 1/2

steeper slow = shorter half life

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6
Q

What is equation for Vd?

A

Vd = A/C = amount of drug / concentration in plasma

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7
Q

What is equation for t 1/2 in one compartment model?

A 
t1/2 = 0.7*Vd/Cl 
Vd = distribution volume
Cl = clearance
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8
Q

What is the two-compartment model?

A

central compartment = systemic circulation + vessel-rich tissue
peripheral compartment = slowly equilibrating tissue [adipose]

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9
Q

What are the two kinetic phases in two-compartment model?

A

early distribution phase

late elimination phase

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10
Q

What is happening in the early distribution phase of two compartment model?

A

drug being removed from central compartment by combo of distribution to peripheral compartment and elimination

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11
Q

What is happening in late elimination phase of two compartment model?

A

peripheral compartment reaches equilibrium with central, elimination is solely responsible for further decline in concentration

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12
Q

How do you calculate Vd after distribution is complete in two compartment model?

A
  • slope of line of elimination phase is extrapolated to t=0 to get Co
    Vd [extrap] = A/Co [extrap]
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13
Q

What is relationship Vd and fraction of unbound drug in plasma?

A

directly proportional - increased fraction unbound –> proportional increase in Vd

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14
Q

What happens to t 1/2 if fraction of unbound drug in plasma increases?

A

t 1/2 increases since Vd is increasing

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15
Q

How do you calculate t 1/2 in two compartment model?

A

choose two concentrations that differ by multiple of 2 within the elimination phase –> time between these is half life

IMPORTANT THAT BOTH CONC ARE IN ELIMINATION PHASE

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16
Q

What happens when drug is infused at constand rate?

A

C approaches steady state value Css

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17
Q

What is true of relationship between infusion rate and rate of elimination at Css?

A

infusion rate = rate of elimination

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18
Q

What is rate of elimination?

A

C*Cl

19
Q

What is equation for Css?

A 
Css = IR/Cl
IR = infusion rate
Cl = clearance
20
Q

How does Vd affect Css?

A

Cd does not affect Css – but if have big Vd it will take a longer time to reach Css because bigger t1/2

21
Q

How long does it take to reach Css?

A

After 4-5 half lives, C has reached 95% of Css

22
Q

After 1 half life how what fraction of Css is reached?

A

50% of Css after 1 half life

23
Q

if infusion rate changes from any Css to a new one, how long does it take to reach the new Css

A

4-5 half-lives

24
Q

How long does it take to get halfway from one C to new Css?

A

1 half life to get 50% of the way

25
Q

What is loading dose [Dl]?

A

Dl = Css * Vd

- administer loading dose at start of treatment to bypass accumulation time

26
Q

How do you determine F [bioavailability] for oral dose?

A 
F = AUCoral / AUCIv
AUC = area under curve for time vs plasma concentration graph
27
Q

How do you calculate amount of drug [A] that enters the body in oral dose from the bioavailability?

A 
A = D*F
A = area
D = dose
F = bioavailability
28
Q

For IV administration what is F [bioavailability]? What is relationship D and A?

A 
F = 1
D = A
dose = amount since its all going straight in to blood stream
29
Q

How can you calculate clearance from F?

A 
Cl = D * F / AUC
Cl = clearance
D = dose
F = bioavailability
AUC = area under curve of time vs plasma concentration graph
30
Q

If absorption is much faster than elimination how can you approximate Cmax?

A 
Cmax = D*F/Vd
D = dose
F = bioavailability
Vd = distribution volume
31
Q

What is equation for initial C after an IV bolus?

A

Co = A/Vd

32
Q

What does slow reabsorption do to peak drug conc in plasma [Cmax] and time it takes to reach Cmax [tmax]

A

slow absorption

  • -> decrease Cmax
  • -> increase tmax
33
Q

What is difference in AUC between two drugs with same bioavailibility but different rates of absorption?

A

same AUC even if one has faster absorption than the other and thus lower Cmax and longer tmax

34
Q

What is difference in tmax and AUC between two drugs with same absorption rate but different bioavailability?

A
  • same tmax

- lower AUC for drug with lower bioavailability

35
Q

What happens in repeated oral dosing?

A
  • 2nd dose given before 1st dose eliminated
  • drug accumulates
  • as avg conc rises, rate of elimination rises
  • when rate of eliminate high enough to remove all previous dose, Css[av] achieved
  • time to reach Css[av] is also 4-5 t 1/2 [same as IV drug infusions]
36
Q

What is equation for repeat oral dosing infusion rate?

A

rate in = D * F / T
D = dose
F = bioavailability
T = time interval between doses

37
Q

What is equation for Css[av] for repeated oral dosing?

A 
Css[av] = D * F / (T * Cl)
D = dose
F = bioavailability
T = time interval between doses
Cl = clearance
38
Q

What is equation for Css[max] - Css[min] in oral dosing?

A

Css[max] - Css[min] = D*F / Vd
D = dose
F = bioavailability
Vd = distribution volume

39
Q

How does slower absorption rate change fluctuations in concentration in oral dosing?

A

slow absorption rate causes smaller fluctuations in C

40
Q

How can you use loading dose in oral therapeutic dosing?

A
  • give loading dose as first dose to get Css[av] without having to wait
41
Q

When is first order kinetics reasonable assumption?

A

C < < Km

42
Q

What happens in drugs with C near or above Km?

A

rate of elimination no longer proportional to C

small increase in dose can produce large increase in C

43
Q

What happens if C > > Km?

A

zero order relation

rate of elimination = vmax

44
Q

What happens to drug if zero order kinetics?

A

drug accumulates because can’t reach a steady state

Physiology Part 2 (19 decks)

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