Principles Of Drug Therapy 4 Flashcards
What are Ke and K?
Ke: measure of ability to elim
K: measure of the size of the hole
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
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
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
What is elim 1/2 life?
How long after admin will drug fall to 50%.
4-5 half lives
Re: elim rate, what’s the prop constant?
Clearance, vol/min
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
Relating CL and k and 1/2 life?
t1/2 = 0.69 x Vd/CL
What are t1/2 and k dependent on?
CL and Vd
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
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
CLtotal?
= CLkidney + CLliver + CLother
Diff between 1st and 0 order?
1st: rate ⬇️ linearly with pressure/con
0: “” independent of “”
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
What order is abs and what does it lead to?
1st order
⬆️ plasma drug conc
Xblood formula?
[X]blood = Xadm/Vblood
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
How does conc of drug in blood vary with time after admin OF A SINGLE DOSE?
Depends on rates of abs, elim and distribution
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?
No
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
