L13, L15- Clinical Pharmacokinetics Flashcards Preview

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Flashcards in L13, L15- Clinical Pharmacokinetics Deck (34):

clinical pharmacokinetics aims to design dosage regimens which...

-optimize therapeutic response of drug
-minimizes adverse reactions of drug


what is the fundamental tenet of clinical pharmacokinetics

there is a relationship between effects of a drug and the [drug] in blood


list and define the 3 important pharmacokinetic parameters

-Volume of Distribution (Vd): measure of apparent space in body to contain blood (theoretical)
-Clearance (CL): ability to eliminate drug
-Bioavailability (F): fraction of drug absorbed into systemic circulation


define Vd (include formula)

-volume required to contain all of the drug in the body at the same concentration as in blood
-V at which [drug] in tissue = [drug] in blood
-not necessarily a possible value

Vd = (amt drug in body) / ([drug] in plasma) = dose / Co


if most of a drug is retained in the vascular compartment, then Vd is (high/low)

if most is in extravascular tissue, then Vd is (high/low)

1- low (more in blood)
2- high (more in tissue)


quinacrine has a (high/low) Vd

High- 50000L in a person with body volume of 70L

(used for malarial and tapeworm infections)


what is the function of Vd clinically

-allows conversion of concentrations of drugs to actual amounts of drugs
-i.e. Loading Dose


define loading dose

amount/dose of drug needed to quickly achieve target plasma concentration


describe method used to determine Vd (include two phases)

-IV bolus given: log[drug] in plasma plotted vs time
-Phase 1- distribution phase
-Phase 2- elimination phase
-expand line from phase 2 to the y-axis to determine Co
-Vd = dose / Co


describe clearance (and its formula)

-volume of blood cleared of drug per unit time

-CL = (rate of elimination) / ([drug] in plasma)


(T/F) most drugs follow first order kinetics (in terms of CL)

T- rate of elimination is directly proportional to [drug], and a constant fraction is eliminated per unit time


why do most drugs follow first order kinetics (for CL)

the mechanisms of elimination via enzymes/transporters are not saturated


during continuous IV drug infusion, describe the % of Css reached in terms of half-life

(Css = [drug] at steady state]
1 half-life: 50% Css
2: 75%
3: 87.5%
4: 93.75%


Once IV drug infusion has stopped, describe the % of drug lost in terms of half-life

1 half-life: 50% drug lost
2: 75%
3: 87.5%
4: 93.75%


give half-life equation

t(1/2) = (0.693*Vd) / CL


steady-state of a drug is reached after __ half-lives

4 (93.75%)


a drug has been considered successfully eliminated after __ half-lives

4 (93.75%)


how is Css affected by infusion rate

(Css = [drug] at steady state)
-directly proportional
-if infusion rate doubles, Css doubles // if infusion rate id halved, Css is halved
-no effect of time required to reach Css (4 half-lives)


list the 2 factors that effect Vd and therefore the half-life of the drug

1) obesity --> inc Vd --> inc 1/2 life
2) pathological fluid --> inc Vd --> inc 1/2 life


list the 6 factors that effect CL and therefore the half-life of the drug

1) aging --> dec CL --> inc 1/2 life
2) inhibit CYP --> dec CL --> inc 1/2 life
3) induce CYP --> inc CL --> dec 1/2 life
4, 5, 6) Cardiac, Liver, Renal failure --> dec CL --> inc 1/2 life


zero-order kinetics is also known as....

saturated kinetics (rate of elimination is constant at Vmax b/c receptors/enzymes are saturated)


list the known drugs with zero-order kinetics

-ASA (high doses)


compare 1st order and Zero order kinetics (in terms of CL)

1st- constant fraction of drug eliminated per unit time; rate of elimination is proportional to [drug]

Zero- constant amount of drug eliminated per unit time; rate of elimination is independent from [drug]


to maintain [drug] in plasma within specific range (therapeutic window) over a long period of time, _________ is used

maintenance dose


to achieve target [drug] in plasma rapidly, ________ is used

loading dose


dosing plans are based on knowing the following....

-min therapeutic [drug], min toxic [drug] (therapeutic window)
-CL of drug
-Vd of drug


define therapeutic window

Low- min therapeutic [drug] (troughs)
High- min toxic [drug] (peaks)


equation for maintenance dose and its factors

Maintenance Dose = dosing rate * dosing interval
-Dosing Rate(ss) = (CL * C) / F ( = rate of elimination(ss))

ss- steady state [drug]


equation for loading dose

Loading Dose = (Vd*TC) / F


compare continuous IV infusion or multiple IV injections with and without loading dose

With loading dose reaches Css immediately, Without loading dose it takes 4 half-lives to reach Css


define accumulation factor (AF) and what it predicts

-drug accumulates in body until dosing stops
-AF = (1 / fraction of dose lost in one dosing interval)
-AF predicts ratio of peak [drug] at steady state to peak [drug] after first dose [i.e. AF = 2 if drug is given every half life, AF = 1/0.5]


smaller doses of drug at shorter intervals reduces...

amplitude of the swings of [drug] between drug doses


how does a slow or extended release formulation of an oral drug affects its [drug] in plasma

-peak [drug] is delayed
-peak [drug] is lowered
-[drug] is higher at later times


doubling the dose of a drug has what effect on duration of the drug's effect

-it extends the duration of the drug by ONE half-life
-it does double the [drug] in plasma, but does not double the effect
-the actual effect is determined by %effect v [drug] curve, which follows Michaelis-Menten curve