W8: Pharmacokinetics

Question 1

Equation for Vd (volume of distribution)

Answer 1

Vd = amount of drug absorbed / plasma [drug]

Question 2

Low Vd:
Location of drug?
High/low absorption?

Answer 2

plasma

low absorption

Question 3

Equation for bioavailability

Answer 3

amount of drug absorbed = amount of drug administered x bioavailability

Bioavailability = 100 for IV
usually used for oral administration

Question 4

Blood flow trajectory in kidney:

glomerulus
peritubular capillaries
afferent/efferent arteriole
interlobular artery/vein

Answer 4

interlobular artery
afferent arteriole
glomerulus
efferent arteriole
peritubular capillaries
interlobular vein

Question 5

Filtrate flow trajectory in kidney:

PT, DT, CD, LOH, BC (Bowman’s capsule)

Answer 5

BC
PT
LOH
DT
CD

Question 6

State 3 main mechanisms for drug excretion by the kidney.

Answer 6

1. Filtration at glomerulus (free drugs; 20% of renal blood flow)
2. Tubular secretion at PT (cation and anion transporters; blood to lumen)
3. Passive reabsorption at DT and CT (lipid-soluble and unionized drugs)

Question 7

__ __ allows ionized compounds and lipid insoluble drugs remain in the tubule and pass into urine

Answer 7

ion trapping

Question 8

Define half-life. What does it measure?

Answer 8

The time required for the plasma drug concentration to decrease by 50% from its original value.
Measures the persistence of drug in PLASMA

Question 9

Define Clearance (units).

Answer 9

Volume of plasma cleared of drug per unit time (how fast drug is eliminated).
(volume/time)

Constant (Cl = Kel x Vd)

Ratio that describes the relationship between the rate of elimination of drug from the body and the plasma concentration
(Cl = rate of drug elimination / plasma [drug])

Question 10

For __ order kinetics, rate of elimination is constant, whereas for __ order kinetics, half-life is constant (zero/first).

Answer 10

For zero order kinetics, rate of elimination is constant, whereas for first order kinetics, half-life is constant

zero order - when metabolism is saturated (elimination no longer depends on half-life but happens at constant rate)

first order - before reaching saturation, rate of elimination is NOT constant (exponential) because of half-life dependence.

Question 11

By __ half-life, 95% of drug will be eliminated

Answer 11

4-5

Question 12

Clearance (Cl) and volume of distribution (Vd) are both variables. T/F

How are they related?

Answer 12

False! they are both constant, properties of drug.

They are directly proportional to each other
Cl = kel x Vd

Question 13

What is kel? Associated with?

Answer 13

elimination rate constant (slope of log scale of drug elimination at first order); associated with half-life

Question 14

One compartment model
vs
Two compartment model

Answer 14

One: consider body as one container that drug spreads homongenously in (log graph: linear)

Two: initially drug spread to one compartment then spread to rest of the body (log graph: alpha and beta phase)

Question 15

Describe log graph of two compartment model and what’s happening in the body

Answer 15

alpha phase: distribution (steep decline - distribution and elimination)
beta phase: elimination (linear - elimination)

Question 16

Half-life of drug is dependent on __ and __.

Answer 16

Vd and Cl; changes in these to can affect half-life

t1/2 = 0.7 Vd/Cl

Question 17

How is half-life affected:

increased Vd
increased Cl

Answer 17

increased Vd: increased t1/2

increased Cl: decreased t1/2