Drug Disposition III Flashcards
Important pharmacokinetic parameters: (5)
Bioavailability
Volume of distribution
First order elimination rate constant
Half-life
Clearance
During time course of drug action, assume ____ concentrations are proportional concentrations at _____ tissue.
plasma
target
Drug action models are especially useful when: (2)
- when magnitude of therapeutic effect cannot be measured clinically
- therapeutic window is narrow
Pharmacokinetic parameters vary substantially in the population and can even change over time in a single patient. True or false?
true
Most drugs are eliminated this way:
first order drug elimination
Constant fraction of drug eliminated per unit time is ___ ____ drug elimination.
first order
The first order elimination rate constant, ____ is the fractional rate of drug elimination.
kE
What are the units for kE?
units of reciprocal time
How do you calculate kE given starting plasma concentration?
For example, starting plasma concentration is 600 ng/ml.
starting plasma concentration * (1-kE)
480 ng/ml
The time required to reduce the plasma drug concentration by 50% is known as _____.
What are the units?
half-life
time
t1/2 is _________ proportional to kE.
inversely
Estimate the half life of the drug:
50% of y-axis, then 1/2 on x-axis in left direction and half in right direction.
Subtract x(greater value) - x(lesser value) = seconds
about 0.7
Calculate half life from Log Plasma Concentration versus time plot
t1/2 =
-0.301/1
What determines duration of action of a single dose?
half-life
___-___ half-lives for a dose to be effectively eliminated
5-6
In ______ dosage schedules, determines time to reach a new steady state when rate of administration changes.
chronic
Together, half life with _____ __ _____, determines choice of dosage interval.
margin of safety
Half life is an _____ process.
exponential
Drug administration is ____ order and elimination is ____ order.
zero
first
Because taking the pill does not depend on plasma concentrations.
What type of curve is this?
Plot of drug absorption and elimination
Elimination rate exceeds absorption so curve peaks
Rate of drug absorption can be affected by: (3)
route of administration
blood flow
slow-release preparations
Slower absorption means (2)
Lower peak concentrations
Longer duration of action
______ plasma concentration is reached under:
- zero order drug administration
- first order drug elimination
Steady-state
Most drugs given _____ every half life.
once
____ _____ , (units of ___) is the volume of plasma from which drug is fully removed per unit time.
plasma clearance
ml/min
CLp = Σ _____organs
CL of all
CLp equation:
rate of elimination
plasma concentration
KNOW
What equation is this?
CSS * CLp
Concentration of steady state * clearance in plasma
Rate of Administration
Half life has nothing to do with steady state. True or false?
Clearance is 1.44 L/kg/h, and its half-life is 1.9 h. At what rate would you need to infuse morphine intravenously to achieve an effective steady state plasma concentration of 65 mcg/L in a 70 kg man?
true
6.5 mg/hr
Clearance (CL) is __________ to half life.
inversely proportional
CL is dependent on Vd. True or false?
false
independent
If your rate of Vd is increased, it is much slower to clear.
It takes__-___ half-lives to reach steady- state.
5-6
KNOW
Time to reach new CSS depends only on the ___
half life
exponential
What can occur if there is an altered clearance of drug, for example people with renal insufficiency?
cumulative poisoning
Therapeutically it is better to reduce dosing rate because ____ ____ at steady state remains the same despite number of doses.
mean concentration
Choice of dose interval depends on balance of the following: (4)
Drug half-life
Size of therapeutic window
Frequency/severity of adverse effects
Convenience and patient compliance
When is a loading dose needed? (2)
drugs with a long T
rapid onset needed for emergency
Total loading dose depends on: (3)
- plasma concentration
- volume of distribution
- bioavailability
Total loading dose=
[(concentration) (Vd)] / F
Note: F is bioavailability
Loading dose is ___ times maintenance dose.
2
like z pack
Single loading dose followed by ______ maintenance doses.
smaller
What is the major goals of drug monitoring and dose adjustment?
refine estimate of clearance
refine estimate of bioavailability
When do you sample when monitoring a drug? (2)
- Allow long enough after dosing for distribution phase to be over
- Usually, best time is right before a scheduled dose
When monitoring a drug it is important to know if the patient is in steady state with a drug. True or false?
true
in order to get an accurate estimate of steady state
Treat the patient, not just the number because: (2)
- Therapeutic window may vary with individuals
- Knowledge of previous plasma concentrations is important
Constant absolute amount of drug is eliminated per unit time is known as:
zero order kinetics of drug elimination
Amount eliminated is independent of concentration of drug remaining at any given time is known as
zero order kinetics
In zero order kinetics, it is possible to reach steady state. True or false?
false
Can NEVER reach steady state!
For oral or other routes, rate of administration equation is:
What are the units?
Css * CLp
F
mg/min
Note: F is bioavailability, CLp is plasma clearance
