01b: Time-Course, Dosage

Question 1

The “therapeutic window” is between which values?

Answer 1

Cp of toxicity and threshold Cp

Question 2

Linearization of Cp(t): what is the x and y axis?

Answer 2

X: time
Y: ln(Cp)

Question 3

Linearization of Cp(t): the slope is (X).

Answer 3

X = KeI, the fraction of drug eliminated per unit time (by all routes)

Question 4

Linearization of Cp(t): the y-intercept is (X).

Answer 4

X = ln(Cpo)

Question 5

T/F: Under first-order conditions of elimination, the elimination half-life is dose-dependent.

Answer 5

False; dose-independent

Question 6

Elimination half-life is dependent on which KEY things??

Answer 6

1. Vd

2. Cl(T) (total clearance)

Question 7

In elimination/clearance following first-order kinetics, (X) is reduced by a constant (fraction/amount) per unit time. And in zero-order?

Answer 7

X = Cp;
Fraction (i.e. half-life)
Amount

Question 8

First-order kinetics: doubling the administered dose will (increase/decrease) the duration of action by (X).

Answer 8

Increase;

X = one half-life

Question 9

T/F: In zero-order kinetics, Cp versus time plot is linear without ln transformation.

Answer 9

True (constant AMOUNT eliminated per unit time)

Question 10

Two-compartment model: plot of (X) versus time. What does alpha-phase represent?

Answer 10

X = ln(Cp)

Equilibration and redistribution of drug from first compartment/volume to second compartment/volume

Question 11

Two-compartment model: plot of (X) versus time. What does beta-phase represent?

Answer 11

X = ln(Cp)

Elimination of drug from body

Question 12

Multi-compartment kinetics: the duration of action depends on (X) process. Thus, this duration may be short, despite a long elimination half-life.

Answer 12

X = redistribution (ex: out of brain to slowly perfused tissues)

Question 13

Single-compartment model with absorption phase: aside from just the dose of drug given, which factors are also considered when calculating initial Cp?

Answer 13

1. Ka (absorption rate constant)

2. F (fraction of dose that’s absorbed/bioavailable)

Question 14

Faster absorption rate, means (higher/lower) Cp(max)
 at a(n) (earlier/later) t(max).

Answer 14

Higher; earlier

Question 15

Determination of drug bioavailability: which data from which plot is used?

Answer 15

AUC (area under Cp v time curve)

Question 16

Absolute bioavailability is determined by which fraction?

Answer 16

AUC (non-IV)/AUC (IV)

Question 17

Relative bioavailability determined by which fraction?

Answer 17

AUC (formulation 1)/AUC (formulation 2)

Question 18

(Abs/rel) bioavailability is used to test new formulations of known drug.

Answer 18

Rel

Question 19

Vd is (greater/smaller) in IV admin than in P.O. admin of drug.

Answer 19

SAME

Question 20

T/F: Elimination half-life is greater in P.O. admin than it is in IV admin of drug.

Answer 20

False - SAME in both

Question 21

T/F: KeI is the same in IV and non-IV routes of drug admin.

Answer 21

True IF Ka (absorption) is greater than KeI

Question 22

Continuous infusion: the infusion rate is equal to…

Answer 22

Cp(SS)*Cl(T)

Question 23

The time when Cp is 50% of Cp(SS) is (X) number of elimination half-lives. And when Cp is 93% of Cp(SS), time is (Y) half-lives?

Answer 23

X = 1
Y = 4

Question 24

Time required to reach Cp(SS) depends on (X). Thus, if you triple (Y), you’ll just have a 3x higher Cp(SS) with the same time required to reach that state.

Answer 24

X = elimination half-life
Y = infusion/input rate

Question 25

Loading dose is administered at (beginning/middle/end) of treatment regimen for which purpose?

Answer 25

Beginning;

To achieve therapeutic Cp level (rapid onset of effect)

Question 26

Loading dose is important for which scenarios?

Answer 26

1. Indication requiring rapid onset of effect

2. Drug with long elimination half-life and slow attainment of SS

Question 27

Loading dose (increases/decreases) Cp(SS) in continuous infusion.

Answer 27

Neither! Doesn’t affect Cp(SS)

Question 28

In multiple-dose kinetics, the rate of achieving steady state is determined by ratio of (X) to (Y).

Answer 28

X = dosing interval
Y = elimination half-life

Question 29

Drug administered in multiple doses at interval about equal to its half-life. What’s the accumulation of the drug at SS?

Answer 29

2x

Question 30

In administration of solid, oral drugs, list the potential rate-limiting steps.

Answer 30

1. Disintegration/release
2. Dissolution (in aqueous env)
3. Absorption (across membrane, into circulation)

Question 31

(X), like starch, are inactive substances in drug products (diluents) that enhance (Y) process.

Answer 31

X = Excipients
Y = disintegration of tablet and dissolution of active drug

Question 32

Smaller drug particle will have (faster/slower) dissolution rate compared to larger particle. Why?

Answer 32

Faster;

Larger surface area

Question 33

Buccal surface administration of drugs provides rapid absorption for (water/lipid)-soluble drugs. What’s a key advantage of this admin route?

Answer 33

Lipid;

Bypass portal circulation and directly to systemic circulation (protects drug from first-pass metabolism)

Question 34

In first order kinetics, how would doubling the dose impact drug duration of effect?

Answer 34

Increase by one elimination half-life

Question 35

T/F: First-order kinetics; Cp increases with dose.

Answer 35

True

Question 36

T/F: First-order kinetics; Total clearance, Cl(T), increases with dose.

Answer 36

False

Question 37

Compression force of tablet refers to:

Answer 37

Force used to create tablet (higher compression force, longer it takes for tablet to dissolve)

Question 38

KB of drug represents:

Answer 38

concentration at which 50% of receptors are occupied

Question 39

T/F: Increasing the rate of infusion changes the time necessary to reach the steady-state concentration.

Answer 39

False