B2.070 - Pharmacokinetics

Question 1

What is acetaminophen

Answer 1

Analgesic

Antipyretic (anti fever)

Question 2

How many hospitalizations and deaths each year due to Tylenol

Answer 2

80,000 hospitalizations

500 deaths

Question 3

What is the therapeutic index

Answer 3

The difference in amount it takes to achieve therapeutic effect and the amount it takes to kill you

Question 4

Types of effects and intensity of effects are proportional to what

Answer 4

Active drug concentration at its sites of action

Question 5

How do drugs get to the site of action? (4 steps)

Answer 5

ADME
A- Absorption
D - Distribution
M- Metabolism
E - Excretion

Question 6

What are the types of absorption

Answer 6

Passive diffusion
Carrier mediated transport
Facilitated diffusion
Active transport

Question 7

What is passive diffusion

Answer 7

Direct passage through lipid bilayers of cell membrane driven by a concentration gradient
Dependent on size and chemical properties

Question 8

What is the most common form of drug absorption

Answer 8

Passive diffusion

Question 9

How does carrier mediated transport work

Answer 9

Transporters facilitate movement of molecules into tissues

Influx or efflux

Question 10

Characteristics of all carrier mediated transport

Answer 10

Structural selectivity
Competition by similar molecules
Saturable

Question 11

What is facilitated diffusion

Answer 11

A type of carrier mediated transport
Facilitates passage of polar or charged molecules
Does not require ATP
Involves movement of a drug down a concentration gradient

Question 12

What is active transport

Answer 12

Energy dependent carrier mediated transport

Question 13

What is the difference between primary and secondary active transport

Answer 13

Primary - transport coupled to ATP hydrolysis

Secondary - cotransport substrate down a gradient

Question 14

What is the most rapid mode of membrane permeation

Answer 14

Active transport

Question 15

What are important sites of active transport

Answer 15

Enterocytes
Hepatocytes
Neuronal membranes
Renal tubular cells
Blood brain barrier

Question 16

What is most absorption of acetominophen

Answer 16

Passive diffusion

Question 17

How long does it take to get maximum plasma concentrations of acetominophen

Answer 17

T max = .5-1 hr

Question 18

What is the bioavailability of acetominophen

Answer 18

.7-.9 = F

Question 19

What is bioavailability

Answer 19

Difference between amount of drug administered and how much actually gets into the blood stream

Question 20

What is distribution

Answer 20

Process of getting out of the blood stream and into the organs

Question 21

What types of drugs stay in blood

Answer 21

Very large molecules (proteins), high charged molecules (heparin)

Question 22

What types of drugs stay in extracellular water

Answer 22

Larger, very polar, water soluble (mannitol)

Question 23

What types of drugs stay in total body water

Answer 23

Smaller, water soluble (ethanol, acetominophen)

Question 24

What types of drugs go to adipose tissue

Answer 24

Lipid soluble (diazepam)

Question 25

What types of drugs go to bone and teeth

Answer 25

Ions, chelates

Question 26

What is the apparent volume of distribution (Vd)

Answer 26

Compartment where a drug appears to distribute

Question 27

What is the extrapolated concentration of a drug in plasma at time 0 after equilibration (Co)

Answer 27

Co=amount of drug / Vd

Question 28

What is the equation for Vd

Answer 28

Vd=amount of drug/Co

Question 29

What compartment has the smallest Vd

Answer 29

Plasma water

Question 30

What compartments have the highest Vd

Answer 30

Tissues

Question 31

How can Vd exceed the actual volume of total body water?

Answer 31

If the concentration in any compartment/tissue is higher than Cp then the V*C production will be higher

Question 32

What is Vd really a measure of

Answer 32

The relative distribution between plasma and the rest of the body

Question 33

What is the importance of Vd qualitatively

Answer 33

Indicates ratio of plasma concentration to concentrations in tissues

Question 34

Which is more useful a qualitative use of Vd or quantitative

Answer 34

Quantitative

Question 35

What are the quantitative uses for Vd

Answer 35

Half life determination | Supports determination of dose required to achieve target drug concentration

Question 36

How do you calculate how much drug is left in a patient

Answer 36

Plasma concentration X Vd

Question 37

Clearance and Vd are inherent properties of a drug what do they represent

Answer 37

CL - primary parameter for elimination | Vd - primary parameter for distribution

Question 38

What are the secondary parameters derived from the primary parameters

Answer 38

``` KeI = CL/Vd = elimination rate constant T1/2 = .693xVd/CL = Half life ```

Question 39

How do you calculate the amount of drug in the body at any given time

Answer 39

Plasma concentration x Vd

Question 40

Where does acetaminophen distributes to

Answer 40

Total body water

Question 41

Efficient excretion of drugs requires what

Answer 41

Water solubility

Question 42

What is phase 1 of drug metabolism

Answer 42

Introduce or unmask a functional group Relatively few atoms involved (usually 1-3) Three major reaction classes (oxidation, reduction, hydrolysis)

Question 43

What is phase 2 drug metabolism

Answer 43

Synthetic (conjugation) reaction Addition of molecules Require specific functional groups

Question 44

what contribute to first pass affect

Answer 44

High activities in enterocytes

Question 45

What’s an example of an adverse reaction due to metabolizing of a drug

Answer 45

Acetaminophen induced hepatotoxicity

Question 46

What are the metabolic pathways of acetominophen

Answer 46

1. Glucuronidation (non toxic) 2. NAPQI - toxic if not GSH involved 3. Sulfation (non toxic)

Question 47

Intestinal enterocytes transporters modulate

Answer 47

Absorption

Question 48

What role does ATP driven transport have in metabolism of acetominophen

Answer 48

Secretion of glucuronide and sulfate conjugated from hepatocyte into bile or blood

Question 49

Amount excreted by any process per unit time is proportional to

Answer 49

Rate of elimination for that process and concentration of drug in plasma

Question 50

Drug concentration in the plasma is inversely proportional to the volume of distribution so drugs with...

Answer 50

Larger volumes of distribution are eliminated slower | Lower volumes of distribution will be eliminated faster

Question 51

What are the major pathways of excretion

Answer 51

Renal | Hepatic, biliary

Question 52

How is acetominophen excreted

Answer 52

In the ruin

Question 53

How is acetominophen excreted in the urine

Answer 53

Glutathione conjugate is further metabolized and excreted in urine as cysteine conjugate and mercapturic acid

Question 54

How do you irreversibly eliminate a drug from systemic circulation

Answer 54

Metabolism | Excretion

Question 55

What’s the equation for elimination rate

Answer 55

Elimination rate = CL x Concentration

Question 56

What’s the unit of measurement for elimination rate

Answer 56

Mg/hr

Question 57

What’s the equation for elimination rate constant

Answer 57

Kei = CL/Vd

Question 58

What is the equation for half life

Answer 58

T1/2 = .693 x Vd/CL

Question 59

What is the equation for clearance

Answer 59

CL = rate of elimination from the body/plasma concentration

Question 60

Total body clearance is what

Answer 60

The sum of hepatic clearance and renal clearance

Question 61

Most drugs follow what

Answer 61

First order kinetics

Question 62

Zero order elimination rate =

Answer 62

K

Question 63

First order elimination rate =

Answer 63

K[drug]

Question 64

In first order kinetics what is rate limiting

Answer 64

Concentration