Principles Of Drug Therapy 4 Flashcards by Natachi Chukumerije

What are Ke and K?

Ke: measure of ability to elim
K: measure of the size of the hole

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What is 1st order elimination?

The rate of ⬇️ in plasma drug conc is prop to the plasma drug conc

The rate of ⬇️ of height in bucket is prop to height of water column

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How does the plasma drug conc change as func of time?

Exponentially, takes same amount of time for conc to drop to half its value

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When does a 1st order process yield a straight line?

Log of drug vs time

ln[X]t = ln[X]0 - ke x t

Slope = ke, if log to base e is plotted

Ke x t1/2 = 0.69, a constant

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What is elim 1/2 life?

How long after admin will drug fall to 50%.

4-5 half lives

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Re: elim rate, what’s the prop constant?

Clearance, vol/min

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What’s the relationship between k and CL?

Same as that of between amount of drug in body and plasma drug conc

Related via Vd

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Relating CL and k and 1/2 life?

t1/2 = 0.69 x Vd/CL

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What are t1/2 and k dependent on?

CL and Vd

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What’s the leaky bucket model?

If heights and hole sizes are = then the rates of leakage from 2 buckets are =

But level falls slower in wider bucket (⬆️Vd)

So, t1/2 is longer and ke is smaller

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What’s the RE (rate of elim) formula? Why’s it important?

RE = CLtotal x [X]blood

Helps us to determine dose to maintain desired [drug]blood

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CLtotal?

= CLkidney + CLliver + CLother

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Diff between 1st and 0 order?

1st: rate ⬇️ linearly with pressure/con
0: “” independent of “”

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How might a drug be 1st order then 0 order?

Some drugs elim by biotransformation or active secretion

May use enz/pumps, so can become saturated (reach Rmax)

1st order at low dose, approach 0 at higher

Blood levels of drugs elim by 0 order kinetics are difficult to control

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What order is abs and what does it lead to?

1st order

⬆️ plasma drug conc

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Xblood formula?

[X]blood = Xadm/Vblood

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What order is distribution and what does it lead to?

1st
⬇️ in plasma conc
Very evident for IV drugs or if abs is really fast

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How does conc of drug in blood vary with time after admin OF A SINGLE DOSE?

Depends on rates of abs, elim and distribution

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What are the kinetics of distr + elim?

Rapid admin of IV:

Xplasma = Xad/Vplasma

No elim:
Xplasma = Xad/Vdistr

After distr: conc falls b/c of elim

Semi log plot of elim is linear for 1st order

What are the kinetics of abs and elim for IV and oral?

After IV:
conc ⬆️ fast then decline and elim

After oral:
Conc ⬆️ as abs happens, when abs ⬇️, elim ⬆️

Abs delays elim

What is Cmax? Tmax? AUC?

Cmax = max plasma conc after single dose

Tmax = time to reach Cmax

AUC = dose(ad) x f/CL (exposure to drug)

What’s determination of Vd(area)?

CL = 0.69Vd/t1/2

AUC can be used to calc Vd

Bioavailability formula? CL? Vd (area)?

AUC(oral)/AUC(IV) = f

f=1 if abs is complete and clearance is same

CL = (dose x f)/AUC

Vd(area) = CL x t1/2/0.69

The effects of dose on Cmax, AUC, Tmax, and DOA?

Cmax and AUC are prop to dose

Tmax and 1/2life are NOT PROP TO DOSE!!

DOA ⬆️ w/ dose, but NOT PROP TO DOSE!!

At certain dose the plasma come will fail to react MEC and DOA will be 0

What's the effect of ⬆️ CL for fixed dose w/ constant abs (ka)?

⬇️: AUC, half life, Cmax, Tmax Term of action is sooner w/ little effect on onset DOA⬇️

What factors may affect CL?

Interactions: I- of secretion, changes in ENTEROHEPATIC cycling Polymorphisms Age/sex Urine pH change affecting reab rates of weak a+bs Disease

Is DOA diff for oral v IV?

When is the diff larger between plasma conc of IV and oral?

IV is much higher Diff is larger when distribution is significant and slow

What happens when you ⬇️ abs rate w/ fixed dose and constant clearance and t1/2?

Abs rates: 1, 1/2, 1/4, 1/8 AUC constant, Cmax ⬇️, Tmax ⬆️ DOA change is complex if MEC is 35 DOA values: 1.6, 1.74, 1.75 and 0 Cmax ⬇️ leads to DOA ⬇️ while TOA⬆️ leads to ⬆️DOA

What are the effects of slowing abs?

- ⬇️ avg blood conc - Will have small effect on DOA over certain range - if ka is slower than ke, elim will not reflect half life (since abs and elim phases overlap thru curve)

What factors affect abs rate?

Site of admin Formulation Drug properties

W/ slow release, if you ⬆️ the dose w/ 1/16th abs rate, w/ normal CL and 1/2life, what happens?

⬆️ plasma drug conc, DOA

DOA of slow vs reg abs drug?

Slow release drug has ⬆️ DOA (5.4 v 1.6) AND onset Same plasma conc

Why do some drugs combine rapid and delayed release forms?

For fast onset and longer DOA

What happens if a high dose formulation is abs rapidly? As in given via IV?

Longer DOA but plasma conc in toxic or lethal range

What does the steady state drug conc (Css) depend on?

The fill rate and size of hole (CL)

What's infusion rate?

= CL x Css For 1st order, CL is a constant

When elim is saturated what's the Css rise relationship to dose ⬆️?

It's NOT PROP!

The safe and effective dose range is wider for?

Drug elim by 1st order

The time taken to reach steady state conc depends on?

Elim 1/2 life/clearance Usually 5 half lives

With mult dosing, plasma conc fluctuate and the choice of dosing interval depends on?

t1/2, MTC, MEC narrower therapeutic range requires more frequent dosing of smaller doses

For intermittent dosing, when do the fluctuations in [D]plasma ⬆️?

If the dosing interval ⬆️ (larger doses) and the rate of abs ⬆️ or Vd ⬇️

What's a loading dose? Formula?

Time taken to reach therapeutic range can be ⬇️ by giving a loading dose **for peak Css max LD = 2 x MD (maintenance dose) **for mean Css max LD = (Css mean) x Vd

Why use loading doses? When might it be harmful?

For slow elim drugs to get into good range quickly Harmful when rate of distribution is slow relative to abs

What does t1/2 depend on?

CL and Vd