DD Frech metabolism excretion

Question 1

In general, what are the Phases of metabolism and what occurs during these phases?

Answer 1

Phase I - drug is made more hydrophilic. Phase II - drug is made very water soluble.

Question 2

Where does Phase I metabolism take place.

Answer 2

Liver smooth endoplasmic reticulum

Question 3

What type of reactions take place in Phase I metabolism?

Answer 3

Oxidations, reductions, hydrolysis

Question 4

What types of enzymes participate in Phase I

Answer 4

CYP450, reductases, esterases-amidases

Question 5

Which phase of metabolism is more susceptible to drug-drug interactions?

Answer 5

Phase I

Question 6

Which phase of metabolism is more likely to be saturated?

Answer 6

Phase II

Question 7

Which phase of metabolism is more susceptible to age related changes?

Answer 7

Phase I

Question 8

What type of reactions take place in Phase II metabolism?

Answer 8

Conjugations

Question 9

What types of enzymes participate in Phase II

Answer 9

Transferases

Question 10

What are the 4 things that can happen to a drug during metabolism?

Answer 10

Detoxify, active drug to more active compound, inactive drug to an active compound, make a toxic metabolite

Question 11

Which phase of metabolism can be induced or inhibited?

Answer 11

Phase I

Question 12

T or F: Hydrophilic drugs can be metabolized by Phase I reactions.

Answer 12

FALSE. They must be lipid soluble otherwise they will have low specificity.

Question 13

What does an Amplichip test tell you?

Answer 13

Detects polymorphisms in metabolism - ultrarapid metabolizers and poor metabolizers

Question 14

Name the 3 highlighted CYP450 dependent drug modifications. (probably want to know these)

Answer 14

Aromatic hydroxylation, aliphatic hydroxylation, oxidative dealkylation

Question 15

Name the 3 highlighted CYP450 independent drug modifications. (probably want to know these)

Answer 15

Amine oxidation (monoamine oxidase), alcohol dehydration, aldehyde dehydration

Question 16

Name the 3 highlighted Phase I reduction drug modifications. (probably want to know these)

Answer 16

Azo reduction, nitro reduction, carbonyl reduction

Question 17

T or F: Phase I esterases are commonly used in the design of pro-drugs.

Answer 17

TRUE

Question 18

T or F: Phase II metabolism is mature at birth.

Answer 18

FALSE. Generally takes longer to mature than Phase I metabolism

Question 19

Describe enterohepatic recirculation.

Answer 19

Absorption in intestines?> goes into circulation?> eventually makes it back to liver ?> into bile ?> resealed back into intestines ?> reabsorbed from intestines

Question 20

What do inducers do?

Answer 20

Produce a qualitative and/or quantitative change/increase in enzyme activity. Generally this is due to an increase in enzyme synthesis, but sometimes induces will also decrease enzyme turnover.

Question 21

Generally, how long do inducers take to affect metabolism?

Answer 21

48-72 hrs. Remember, most inducers cause increased enzyme synthesis, so they act as transcription factors, which means they will take a little more time to have effect.

Question 22

Do inducers affect Phase I or Phase II metabolism?

Answer 22

They can affect both, but most are known to affect CYP450 (Phase I)

Question 23

What do inhibiters do?

Answer 23

Produce a qualitative and/or quantitative decrease in enzyme activity.

Question 24

Generally, how long do inhibitors take to affect metabolism?

Answer 24

Within hours

Question 25

Name the mechanism by which metabolism inhibitor can work (4 things).

Answer 25

1.) Inhibit enzyme synthesis 2.) Compete for enzyme active site 3.) Allosterically inhibit enzyme 4.) Destroy or permanently disable enzyme

Question 26

Do inducers affect Phase I or Phase II metabolism?

Answer 26

They can affect both, but most are known to affect Phase I

Question 27

What is pharmacokinetic tolerance?

Answer 27

Induction of a drug by its own metabolite.

Question 28

Diseases of ______ (organ) may have a profound affect on metabolism.

Answer 28

the liver

Question 29

What type of proteins move molecules out of cells?

Answer 29

P-glycoproteins

Question 30

Which drug from this unit inhibits p-glycoproteins?

Answer 30

Erythomycin (resulting in prolonged Lipitor levels in circulation)

Question 31

Which drug from this unit induce p-glycoproteins?

Answer 31

Rifampin and St. John?s Wort (rifampin increases elimination of oral contraceptives)

Question 32

T or F: Death of bacteria flora can affect hepatoenteric recycling.

Answer 32

Yes, especially if drug absorption is dependent on gut bacterial enzymes.

Question 33

T or F: Most drugs cross into breast milk.

Answer 33

TRUE. Usually at low levels.

Question 34

T or F: Milk is more basic than plasma.

Answer 34

FALSE. Milk is usually more acidic

Question 35

T or F: When choosing a drug during breastfeeding, pick one that is more lipid soluble.

Answer 35

FALSE

Question 36

T or F: When choosing a drug during breastfeeding, pick one that has higher protein binding.

Answer 36

TRUE. It will stay in the plasma rather than go into your mommy fountains

Question 37

T or F: If a highly soluble drug is eliminated via lungs, increasing your respiration rate will increase elimination.

Answer 37

TRUE

Question 38

T or F: If a poorly soluble drug is eliminated via lungs, increasing your respiration rate will increase elimination.

Answer 38

FALSE. Increasing blood flow to lungs increases the elimination of this drug.

Question 39

Define first order kinetics.

Answer 39

The rate of elimination is proportional to the concentration of drug in the plasma.

Question 40

How many half lives does it take to be reasonably sure that a drug is out of the body.

Answer 40

4-5

Question 41

What is steady state?

Answer 41

The state in which plasma concentration is constant. Amount in = amount out. Steady state is generally reached in 4-5 half lives.

Question 42

Does drug dose change the time it takes to reach steady state?

Answer 42

No. Time to steady state is independent to drug dose. However, drug concentration does influence the plasma concentration (Cp) when steady state is reached.

Question 43

What factor does change the time to steady state?

Answer 43

Drug half life

Question 44

If a drug?s half life is 2 hrs, what will be the change in plasma concentration if the drug is not given for 6 hrs?

Answer 44

8 fold fluctuation (2^3) in concentration

Question 45

Define zero order kinetics.

Answer 45

The amount of drug eliminated per unit time is constant and not dependent on drug concentration.