L6 Pharmacokinetics III

Question 1

What is the goal of the biotransformation and metabolism of drugs?

Answer 1

To promote their elimination from the body

Question 2

Drugs with a MW > 350 are excreted how

Answer 2

In the bile

Question 3

What is an example of a drug that must be metabolized to be active?

Answer 3

Codeine

Question 4

What is an example of a drug whose metabolites are more active than the parent drug. What does this do to its half life?

Answer 4

Diazepam. Increases half life OBVIOUSLY

Question 5

What is an example of a drug that gets metabolized to toxic metabolites?

Answer 5

Acetaminophen

Question 6

What toxic pathway does ethanol induce for acetaminophen metabolism?

Answer 6

CYP 2E1

Question 7

What do Phase I reaction do?

Answer 7

Convert lipid-soluble, non-ionized compounds into more ionized, hydrophilic metabolites

Question 8

What do Phase II reactions do?

Answer 8

Add an ionized, charged particle to a phase I metabolite in order to form a more polar and hydrophilic conjugate

(Conjugation)

Question 9

What is the most common type of phase I reaction?

Answer 9

Oxidation

Question 10

What kind of drugs get transferred to the fetus ?

Answer 10

BASIC drugs

Fetus is acidic

Question 11

For first order drugs, what kind of graph should we make to make it easier to interpret?

Answer 11

Semilogarithmic

Question 12

How long does it take to eliminate most of a drug?

Answer 12

5 half lives

Question 13

How long does it take to obtain Css plasma levels

Answer 13

5 half lives

Question 14

How long does it take to determine Css levels?

Answer 14

5 half lives

Question 15

Is the time it takes to reach Css related to the size of the dose?

Answer 15

No, it is related to half life

Question 16

If you decrease “tao” what will happen to Css?

Answer 16

It will increase

You’re giving the drug more often

Question 17

When you’re drinking alcohol, do you ever reach a Css?

Answer 17

No, it just keeps accumulating

Question 18

How do you calculate clearance?

Answer 18

CL= Vd x (.7 / T 1/2)

Question 19

What is CL?

Answer 19

Measure of the body’s capacity to eliminate a drug

Question 20

What is the optimal dosing interval?

Answer 20

The same amount of time as the half life

Question 21

WHat is the most optimal maintenance dose?

Answer 21

When it is equal to the elimination rate

Question 22

If you increase dose and the decrease the dosing interval by the same ratio, what will happen to the Css?

Answer 22

It wont change

Question 23

What kind of metabolism do CYP450’s do?

Answer 23

Phase I

Question 24

What P450 enzyme metabolizes over 50% of drugs?

Answer 24

3A4

Question 25

What P450 enzyme gets a polymorphism that impairs codeine metabolism?

Answer 25

2D6

Question 26

What enzyme metabolizes and is induced by alcohol

Answer 26

2E1 | 21 years of age to drink EtOH

Question 27

Are Phase I microsomal enzymes (CYP 450’s) inducible?

Answer 27

Yes

Question 28

WHat is the only Phase II enzyme that is microsomal and inducible?

Answer 28

Glucuronyl transferase

Question 29

Drugs metabolized by 3A4 have a _____ degree of interactions

Answer 29

High

Question 30

What is the only phase II enzyme that can be induced?

Answer 30

Glucuronyl transferase

Question 31

What does it mean if a drug “induces” an enzyme?

Answer 31

It means the enzyme increases in number and the drugs it metabolizes get disposed of faster (They work less)

Question 32

Fluoxetine inhibits which enzyme?

Answer 32

2D6. | So you’ll have increased concentrations of codeine and oxycodone

Question 33

Grapefruit juice inhibits which enzyme?

Answer 33

3A4. | So you’ll have increased concentrations of APAP, diazepam, and lidocaine

Question 34

What are the OXIDATIVE Phase I reactions that are NOT CYP450’s and not microsomal and inducible?

Answer 34

Alcohol dehydrogenase Monoamine oxidase

Question 35

What are the NON-oxidative Phase I reactions that are not CYP450 and not inducible?

Answer 35

Reductive reactions (warfarin gets a H+) Hydrolytic reactions (esterases and amidases like succinylcholine and AChE)

Question 36

What enzyme does most Phase II reactions?

Answer 36

UDP glucuronyl transferase

Question 37

What is a drug that goers through phase II before phase I?

Answer 37

Isoniazid. It gets acetylated first and then goes through hydrolysis

Question 38

What drug is used to measure activity of CYP 2D6

Answer 38

debrisoquin | Tells you how well they will metabolize codeine

Question 39

What enzyme metabolized nortriptyline?

Answer 39

2D6

Question 40

What type of polymorphism is the alcohol flush reaction?

Answer 40

Phase I polymorphism | Deficient in alcohol dehydrogenase

Question 41

Butyrylcholinesterase and fast/slow acetylators are which type of polymorphism

Answer 41

Phase II

Question 42

If someone is a slow acetylator, according to isoniazid, what should you do to their dose?

Answer 42

Lower it

Question 43

What kinds of drugs are subject to enterohepatic circulation and “freeing” by bacteria?

Answer 43

Large drugs like estrogens

Question 44

What happens to the half life of drugs that undergo enterohepatic circulation

Answer 44

Longer half lives (bacteria remove conjugation and it re-enters circulation)

Question 45

What form are antibiotics given in?

Answer 45

Conjugated form

Question 46

Why do antibiotics affect birth control?

Answer 46

Because estrogens are given in conjugated form and if you kill the bacteria that would take that conjugate off and make it active, its not gonna be active

Question 47

What is the first organ system to mess up in old people

Answer 47

Renal

Question 48

Where do hydrolysis reactions take place

Answer 48

Plasma

Question 49

How many passes through the kidney does it take to clear penicillin

Answer 49

Just 1

Question 50

What enzyme acetylates isoniazid?

Answer 50

N-acetyltransferase

Question 51

Is n-acetyltransferase inducible?

Answer 51

NO