Lecture 1 pharmacokinetics

Question 1

What is Bioavailabilty (F)?

Answer 1

• % of medication that reaches systemic circulation

- IV drugs have a 100% bioavailability

Question 2

Digoxin tablet: F=0.7
Digoxin elixir F= 0.8
Currently taking 250mcg of tablet. How much elixir is equivalent?

Answer 2

• New dose= (F old med x current dose)/F new med

(0. 7 x 250mcg)/0.8= 218.75 mcg of elixir.

Question 3

Levothyroxine:
Oral tablet bioavailability = 50%
PO dose= 100mcg, then IV dose= ?

Answer 3

50mcg

New dose= (F old med x current dose)/F new med
IV dose = (.5 x 100mcg)/ 1 [IV drugs have 100% bioavailabiltiy]
IV dose =50 mcg

Question 4

List what factors influence a drug’s bioavailibility.

Answer 4

-dissolution and absorption characteristics
-Route (IV vs PO, IM)
-Stability in GI tract
Metabolism prior to blood stream (first pass of the liver)

Question 5

First Pass Metabolism is:

Answer 5

The vessels that absorb nutrients, fluids and medications from the GI tract take blood directly to the liver for detoxification before joining into general venous circulation back to the heart.

-90% of oral medication is metabolized and destroyed by the liver before it gets into the general circulation.

Question 6

T/F: only oral medications participate in first pass metabolism in the liver.

Answer 6

True

Question 7

Loading dose = Vd x Cd

Vd=Volume distribution
Cd=Concentration desired.

Calculate the loading dose of vancomycin (Vd=0.7L/kg) for a 70kg patient. Desired concentration = 30mg/L.

Answer 7

0.7Lx30mgx70kg=1470, round to 1500mg of Vancomycin

Question 8

Protein binding:

T/F: only drugs bound to albumin are “active”

Answer 8

False.

unbound/free drug = active.
low albumin=more free drug and vice versa.

Acidic drugs bind to Albumin
Basic drugs bind to alpha 1 acidic glycoprotein.

Question 9

T/F: the fetus is exposed to nearly all medications a mother takes.

Answer 9

True

Question 10

_____ is the reservoir for lipid soluble drugs

Answer 10

Fat, adipose tissue (3rd compartment)

Question 11

____ is a family of transporter proteins that are found all over the body including the blood-brain-barrier. Important for medication interactions and drug resistance

Answer 11

P-glycoproteins

Question 12

Does passive diffusion require a carrier or energy?

Answer 12

Neither.

Passive diffusion O2 or CO2 exchange

Question 13

T/F: Facilitated diffusion uses a carrier and energy.

Answer 13

False, a carrier only. No energy is expended.

Question 14

Which one uses both a carrier and energy for transport?
Aqueous Channels
or
Active Transport?

Answer 14

Active Transport.

Aqueous Channels do not use carriers or energy. (electrolytes)

Question 15

Metabolite:

Answer 15

Anything other than the original drug. The resultant compound after any stage of metabolism

Question 16

T/F: A prodrug is any substance that enhances the effect of a drug on the body.

Answer 16

False: prodrug = active metabolites.

Question 17

CYP450 Inhibition=

Answer 17

Will inhibit the enzyme from working properly and DECREASE the rate of elimination of a drug causing more of the drug to remain active.

Question 18

CYP450 Induction=

Answer 18

Will enhance the capability of the enzyme and therefore accelerate the rate of drug metabolism. May need to redose sooner.

Question 19

Name some factors that affect drug metabolism

Answer 19

• Genetics
• Environmental and diet (however no convincing data for diet- per Emily)
• Disease factors (Liver/kidney)
• Age and sex (not until age 17 do people have full CYP Enzyme Array)

Question 20

____ is/are the major organ of drug excretion.

Answer 20

The kidneys

Question 21

____is/are the major organ of drug metabolism and manufacturer of CYP enzymes.

Answer 21

The Liver

Question 22

To be eliminated/excreted through the kidneys, a drug needs to be _____.

Answer 22

• polar (charged ions)/hydrophillic

- small

Question 23

In First order kinetics for drug elimination, the length of half-life is ________.

Answer 23

Constant.

• Elimination is a constant percentage of the remaining med at each interval. (ex. 10% of the remainder at each half-live).
• Graph has a rounded curve.

Question 24

In Zero order kinetics for drug elimination, the length of the half-life ______.

Answer 24

Decreases as the concentration decreases (each subsequent half life is shorter).

• Constant amount is eliminated each time. (10 units is eliminated at each interval)
• straight line slope
• Zero order kinetics is more common.

Question 25

Elimination rate (k): fraction or % of the total amount of drug in the body removed per unit of time.

k=Cl/V

Cl=clearance
V=Volume
Natural log=ln

k=ln(C1-C2)/Time
t1/2 = 0.693/k

t=ln (C1-C2)/k

Answer 25

FYI. Know these for calculating half-lives.

Question 26

It takes _____ half-lives to reach steady state.

Answer 26

5

Question 27

One sample drawn at 1100am = 13.5mg/L. The second sample drawn at 1600 = 5.8mg/L. K=? t1/2=?

Answer 27

ln(13.5-5.8)/5 hours
ln7.7/5
k=0.408

t1/2=0.693 (0.408)
t1/2=1.7 hour half life

Question 28

A medication is toxic at 55mg/L. Toxicity happens at concentrations >35mg/L. k=0.12. How long until the patient is below toxic concentrations?

Answer 28

t1/2=0.693(0.12)
t1/2=5.6 hour half life

t=ln(55-35)/0.12
t=ln20/0.12
t=2.99/0.12
t=24.96 rounded to 25 hours to non toxic level.

Question 29

Pharmacokinetics is:

Answer 29

described as what the body does to a drug, refers to the movement of drug into, through, and out of the body—the time course of its absorption, bioavailability, distribution, metabolism, and excretion.