Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
120 Cards in this Set
- Front
- Back
|
Compartemtnal modeling is a CONCEPTUAL aid to explain the behisvior of drug levels
|
YES
|
|
|
Do the compartemtn represent certain organs or have antaomical definiation
|
NO
|
|
|
What is the most basic compartematal model
|
IV BOLUS DOSE ONE-COMPARTMETNAL MODEL
|
|
|
What are the IV Bolus Dose ONe-Compartment Model Assumptions:
|
1. Distribution equilibrium is reach instantensouly
2. No drug is eliminated during infusion 3.CL and V are constant and do not vary with dose or conc 4. Drug elimination from the compartment following first-order elimination |
|
|
What does Co=
|
dose/volume of body
|
|
|
What is the dose
|
is the amount that reaches the circulation
|
|
|
Bioavailablity(F) is the fraction reaching the circulation IV dosing F is
|
100% or 1
|
|
|
Rarely drugs can be part salt and the actual drugs amount is a fraction known as
|
S--which can be between 0-1
|
|
|
What are 2 fundamental physiological "processes" that control elimination
|
Drug Clearnnce (CL)
VOlume (V) |
|
|
What is CL
|
rate at which drug is removed from the plasma (L/hr) the VOLUME OF drug that is cleared from the plasma per HR
|
|
|
What is V
|
total appartent volume need to related the drug conc measure to the dose given
|
|
|
The rate of concentration decline depends on
|
CL (volume/time) and V (the total volume needed to clear
|
|
|
What is Ke
|
CL/V units are time-1 (hr-1)Ke
exp 0.6--60% of drug is removed in 1 hr |
|
|
Ke =CL/V it is AKA
|
seondary PK parameter
|
|
|
What aree the primary PK parametners
|
CL and V
|
|
|
Ke is what type of reaction and why
|
1st orer reaction b/c CL process is
|
|
|
What is a first order reaction
|
the rate changes as the amt of drug changes
|
|
|
In first order is a constant FRACTION of drug lost in a given time
|
YES
|
|
|
The constrat FRACTION that is lost is determined by
|
the rate contast ke
|
|
|
Calculation for Rate of loss for 1st order
|
amt of drug in bodyA1(mg) X Ke= rate of loss mg/hr
|
|
|
IN Zero order the reaction rate is
|
the amt of drug that is loss is constant over time
|
|
|
Zero order means that a CONSTANT amount of drug is
|
LOST OVER TIME
|
|
|
If you are losing a constant amount over time does your rate of loss change
|
NO
|
|
|
If you are losing a CONSTANT fraction over time does rate of loss change
|
YES rate changes
|
|
|
When does Zero order occur
|
when drug metabolism is saturated
|
|
|
Is Zero-roder eliminiation common
|
NO--NOT COMMON (phenytoin is an example)
|
|
|
What does 1st order kinetics indicate for the system of drug removal
|
that the system for drug removal is working well below is maxiumal capcaity and is NOT saturated
|
|
|
What does 0 order kinetics indicate
|
the system is working at its capacity and is SATURATED
|
|
|
1st order reactions drug loss with plasam conc over time we get
|
logartirhimic curve
|
|
|
In 1st order reactions if plotted on a semi-log graph we get
|
single slope linear relationship
|
|
|
Elimination half-life (t1/2)=
|
0.693/K
|
|
|
What is Volume equal to V=
|
Dose(amt)/Co(int conc)
|
|
|
Ke is eqaul to CL/V or
|
ln (C1/C2)/t
|
|
|
How many half-lives does it take for a drug to be completely eliminated
|
Take 5 half-lives for a drug to be completly eliminted
|
|
|
Universal equation for AUC
|
Dose*F*S/CL
|
|
|
Does Volume affect AUC
|
NO--affects shape
|
|
|
Loading dose=
|
Volume x desired conc plasma levek
V X C |
|
|
When are continous infusion are used in two general types of clinical situation
|
1. The drug has a short-half life
2. Due to severity of the disease state |
|
|
What does infusion rate (Ro)=
|
Dose (S)(F)/dosing frequency
|
|
|
Should infusion rate be calculated in mg/hr
|
YES
|
|
|
What are one-compartment model assumption of continous IV infusion
|
1.Distribution equalibirium is reach instaneously
2. No drug is eliminated during infusion 3. CL and V are constant 4. Drug eliminatino occurs by first-order elimination |
|
|
The steady steate concentration is a fuction of
|
drug admintratino rate (Ro) and CL only
|
|
|
Css=
|
Ro/Cl
|
|
|
What is CSS
|
the condition where the rate of drug administration (RO) is equal to the rate of drug elmination (rate in=Rateout)
|
|
|
How do you calculate concentrations prior to reaching Css
|
CSS * fraction of ss obtained
C=Css*(1-e-kt) |
|
|
The 5 1/2 rules is the time it takes for a drug to be completly eliminated, it also means
|
the time to reach steady state, and the fraction remaining after a dose
|
|
|
How long does it take to reach SS (steady sate)
|
5 half lives so calculate half-life
|
|
|
Does volume influence Css
|
NO
|
|
|
What does volume influence
|
Ke (CL/V) and 1/2 life VOLUME INFLUENCES TIME TO REACH SS
|
|
|
AUC depends on Css and CL, what does V do
|
alters the shape of drug conc
|
|
|
IN continous influsions what does Volume tell use
|
loading dose, how much needed to fill the tank
dose=VxC(desired of plasma) |
|
|
IN continous infusions CL is considered, and tell us
|
considered the "maintaince dose" and tells us what dose is needed to "keep the tank full"
|
|
|
Dose rate =
|
Cl*Css
|
|
|
What are 2 ways you can calculate concentrations after stopping infusion
|
1.After Reaching Css
2. Prior to Reach Css |
|
|
How do you calculate stopping the infusion after reaching steady state
|
Ct=Ro/CL*(e*-ke*(t2-T2)
|
|
|
What is equation for stopping the infusion prior to reaching steady state
|
C=Ro/Cl*(1-ke*-kt1)*(e-k*(t2-t1)
|
|
|
When do we use the short infusion model
|
When the bolus is NOT at least 6x faster than the elimination half life
|
|
|
We can only assume no DRUG is elminated during a BOLUS when
|
the bolus is infused 6x faster than the elimination half-half
|
|
|
If drug is eliminated what do we use
|
Short-infusion model, b/c this accounts for drug loss
|
|
|
What is calculation for short-infusion model (peak conc after infusion)
|
(Dose/tin)/CL)*(1-e*-k*tin)
|
|
|
After calculating the max peak levels on an infusion, then you can calculate concentrations after anytime later calc=
|
C=C(end of infusion)*e-k(t2-t1)
|
|
|
If we give both an infusion and loading dose started at same time what is equation
|
IV Bolus dose+ IV infusion
|
|
|
Cplasma=
|
C(LD)+C(inf)
|
|
|
ALWAYS CALCULATE HALF-LIFE TO DETERMINE IF REACHED STEADY STATE OR NOT
|
YES
|
|
|
What is drug absorption
|
the process by which drugs cross body membranes and enter the bodysteam
|
|
|
What are two elements of drug absoprtion
|
1. rate at which a drug leaves its site of adinistration
2. Extents (F) to which this occurs |
|
|
What is the absorption lag-time
|
some drugs need time to dissolve in the stomach and gain access to small intestine
|
|
|
What type of products have a lag-time of rising concentrations
|
EC products have a lag time
|
|
|
Once absoprtion begins drug eneters the circulation at a rate define by
|
Ka--the absoprtion rate constant with units of time -1
|
|
|
The Ka for most oral drugs is what type of reaction
|
1st order and rapid
|
|
|
Many oral drugs reach the peak plasma concentration within
|
1-2hrs
|
|
|
Does ka impact the EXTENT of absorption or AUC
|
NO
|
|
|
Rate of Change of drug in the body=
|
Rate of absorption-Rate of elimination
|
|
|
Rate of absoprtion =
|
ka*[Aa}
|
|
|
What is the rate of elimination eqaul to
|
ke *[A]
|
|
|
When the conc of drug is greater in the absoprtion phase what does this mean
|
its in the absoprtion phase
|
|
|
Whhen the conc of drug is greater in the elimination phase what does this mean
|
it is in the elimination phase
|
|
|
When the conc of drug are equal in the absoprtino and elimination phase what does this mean
|
it is the Conc MAX
|
|
|
Aa is the amt at
|
the absoprtion site
|
|
|
A is the amount that
|
has reached the circulation
|
|
|
What does Ka affect
|
Cmax and Tmax
|
|
|
The slower the Ka
|
the lower the Cmax,and SLOWER tmax
|
|
|
Why is the equaltion for Ka worthless
|
ulike V and CL, ka changes
|
|
|
When does Ka change
|
dosing after a heavy meal slows Ka
dosing on a empty stomoch increase ka |
|
|
Does Ka affect the overal exposure to AUC
|
NO
|
|
|
When a drug is rapidly absorption and it peaks in 1-2 hrs we use what to predict conc
|
Bolus equation
C0=dose/V C2=C1*e(-k*t2-t1) |
|
|
What a drug is Sustained release or pacth is controlled release this is analgous to
|
constant infusion
Css=Ro/Cl |
|
|
What is RO equal to in controlled release
|
dose (F)(S)/ (dosing frequency)
|
|
|
What type of polyetpides can pass through the capillary pathway and enter the blood
|
polypeptides <5000MW
|
|
|
Larger proteins greater than what enter the blood via lympathic patways
|
>20,000
|
|
|
Lymph flow is slow therefore absroption from nonvascular parentalsites can continue
|
for many hours
|
|
|
Putting drugs in SQ does what equation
|
constant infusion effect
|
|
|
What are 2 fundament PK parameters than define absroption
|
1.Absoprtion rate constant (ka)
2.Bioavailability |
|
|
The absoprtion rate constant (ka) directcly impacts
|
Cmax and Tmax (not AUC_
|
|
|
We many use ka to tell us wherther "bolus" or "infusion" equations can be used
|
YES
|
|
|
Bioavailablity the EXTENT of absorption directly impacts
|
AUC
|
|
|
Dose delivered =
|
Dose *F
|
|
|
Can the AUC also be calculated using the trapezoidal method
|
YES
|
|
|
The trapezoidal AUC method is AKA non-compartmetnal anaysis
|
YES
|
|
|
IF F is not known that AUC from oral dosing yields
|
CL/F=dose/AUC
|
|
|
Chronic dosing tpyically includes a
|
FIXED DOSE, and FIXED TIME interval
|
|
|
WHat is an example of a FIXED dose and FIXED time interval
|
take two tablets every 12 hours
|
|
|
Fixed dose internal is called
|
tau (t) hours
|
|
|
What is the dosing rate in chonirinc dosing
|
dose/(t)
|
|
|
When drugs are administered in fixed dose and fixed time internal what happens if there is drug left in the body before next dose
|
the conc rises towards a platuea which represent SS
|
|
|
When giving chronic dosing treat situation as what other type of dosing
|
constrant infusion
|
|
|
What is the equation for fixed dosing over a fixed interval
|
CSS= RO/CL
|
|
|
What does Ro eqal in fixed dosing over a fixed interval
|
dose(F)(S)/(t)
|
|
|
What is problem with calculating the Average Css in dosing
|
as long as the medication have the same daily dose same Css--but maxium and minimmun differ consideranbly
|
|
|
When are the Cmax, Cmin and Css much different
|
when the dose interval is long and the half-life of the drug is short
|
|
|
When the half-life is > or= 3x LONGER than (t) then
|
Cmax, Cmin and Css are close to the same and the Css equaction can be used ANYTIME in the interval
|
|
|
When Cmax and Cmin differ from Css, notice that compared with the 1st dose, the (Cmax,Cmin, are elevated by a certain factors AKA
|
acuculmation factor
|
|
|
What dose the acumulatino factor determine
|
how much drug is gain at steady state compared with the first dose for a given dosing interal
|
|
|
What is the accumlatuion ratio
|
1/(1-e*-k(t) (recepiroal of the fraction lost is the fraction grain
|
|
|
The acumulation ratio can be used for SS calculation fo
|
Bolus dosing PK
Short infusion PK |
|
|
What is First dose calculation for Bolus Dosing PK at SS (with multiple dosing)
|
C0=dose(F)(S)/V
co=cman |
|
|
WHat is First dose Cmin
|
Cmax*e-k(t)
|
|
|
SSCmax=
|
Cmax/(1-ek(t)
u need to account for the fraction gained from multiple dosing |
|
|
SSCmin
|
SSCmax*(e-k(t)
|
|
|
How do you calculated Cmax after a certain # of doseses
Cmax(nth dose)= |
SSCmax*(1-e*-(k)(N)(t))
|
