Pharmacology - Drug Metabolism and Excretion (Exam 1)

Question 1

The general purpose of drug metabolism and excretion is to make the drugs more ______ soluble, so they will be excreted and not reabsorbed

Answer 1

water

Question 2

Where does biotransformation occur?

Answer 2

many organs, but the LIVER is the most important

Question 3

What are the 2 biotransformation reaction subdivisions?

Answer 3

1. non-synthetic (oxidation, Phase I)
2. synthetic (conjugation, Phase II)

Question 4

What is a non-synthetic reaction?

Answer 4

addition of COOH, NH2, O, OH, SH

Question 5

What is a synthetic reaction?

Answer 5

addition of group from endogenous cofactor (usually transferring something)

Question 6

In a Phase I oxidation reaction, what is inserted into the drug or side product?

Answer 6

oxygen (usually OH group)

Question 7

The insertion of oxygen into the drug or side product in Phase I oxidation reaction causes what to happen?

Answer 7

makes drug more hydrophilic (less lipophilic)

Question 8

In a Phase I oxidation reaction, the reaction is catalyzed by which enzyme systems?

Answer 8

1. cytochrome P450 system
2. mono-oxygenase system
3. mixed function oxidase system

Question 9

What CYP families are responsible for most drug oxidation?

Answer 9

CYP1, CYP2, and CYP3

Question 9

What are the components of the P450 system?

Answer 9

1. smooth ER
2. cytochrome P450
3. NADPH cytochrome P450 reductase
4. molecular oxygen
5. NADPH

Question 10

Put the following CYP families in order of importance:
CYP2D6, CYP2C, CYP3A

Answer 10

CYP3A (most important)
CYP2D6
CYP2C

Question 11

Which CYPs are important for many clinical drugs?

Answer 11

CYP2C and CYP2D

Question 12

Which CYP in the GI tract is important for the 1st pass effect?

Answer 12

CYP3A4

Question 13

What are the 3 non-P450 oxidation reactions?

Answer 13

1. alcohol and aldehyde oxidation
2. purine oxidation
3. monoamine oxidation

Question 14

What are the other 4 metabolic reactions?

Answer 14

1. azoreduction
2. nitroreduction
3. ester hydrolysis
4. amide hydrolysis

Question 15

What are the Phase II (conjugation/synthetic) reactions?

Answer 15

1. glucuronidation (MOST COMMON)
2. acetylation
3. glutathione conjugation
4. glycine conjugation
5. sulfation
6. methylation

Question 16

What type of enzyme is used for the Phase II (conjugation/synthetic) reactions?

Answer 16

transferases

Question 17

What are the factors affecting drug metabolism?

Answer 17

plasma protein binding, localization of drug in tissues, liver disease, and drug-drug interactions

Question 18

Which drugs inhibit the cytochrome P450 system?

Answer 18

Cimetidine
Azole antifungals (ketoconazole)
Macrolide antibiotics (erythromycin)

Question 19

During the induction of drug metabolism, there is an increase in ________ _________ proteins

Answer 19

cytochrome P450

Question 20

During the induction of drug metabolism, _______ are classical and broad inducers that induce P450 to be produced

Answer 20

barbiturates

Question 20

During the induction of drug metabolism, environmental ________ also induce more selectively

Answer 20

carcinogens

Question 21

During the induction of drug metabolism, chronic ______ induces CYP2E1

Answer 21

alcohol

Question 22

What are the 5 miscellaneous factors affecting drug metabolism?

Answer 22

1. age
2. diet
3. disease
4. other drugs
5. environmental chemicals

Question 23

During the formation of toxic metabolites, _______ intermediates form and bind to cellular macromolecules

Answer 23

electrophilic

Question 24

The formation of toxic metabolites causes _________, ________, and __________.

Answer 24

necrosis, mutagenesis, and carcinogenesis

Question 25

During the formation of toxic metabolites, ___________ conjugation is the first defense

Answer 25

glutathione

Question 26

What are the principal excretion routes?

Answer 26

1. renal (most important) 2. biliary 3. pulmonary 4. miscellaneous (saliva, sweat, tears, milk)

Question 27

What are the routes of renal excretion?

Answer 27

glomerular filtration, active tubular secretion, active tubular reabsorption, passive reabsorption

Question 28

Where does glomerular filtration happen?

Answer 28

at the glomerular membranes

Question 29

What is the capacity of glomerular filtration?

Answer 29

180 L/day 20% of plasma (high capacity)

Question 30

What are the requirements for drug filtration through the glomerulus?

Answer 30

-not too big -not bound to plasma proteins -lipid solubility/pH do NOT effect

Question 31

How are anions and cations involved in active tubular secretion?

Answer 31

-organic anion transporters (OATs) -organic anion transporter peptides (OATPs) -organic cation transporters (OCTs)

Question 32

(T/F) Active tubular secretion is saturable

Answer 32

true

Question 33

(T/F) Active tubular secretion and biliary excretion are incompletely developed in a newborn

Answer 33

true

Question 34

Is active tubular secretion specific or non-specific?

Answer 34

non-specific (causes competition)

Question 35

During active tubular secretion, inhibition by drugs such as probenecid can depress renal excretion of other ______ _______ (ex: penicillin)

Answer 35

weak acids

Question 36

What is the location and characteristics of active tubular reabsorption similar to?

Answer 36

active tubular secretion

Question 37

During active tubular reabsorption, what is it important to conserve?

Answer 37

endogenous compounds (ex: uric acid)

Question 38

What drugs inhibit active tubular reabsorption?

Answer 38

uricosuric drugs

Question 39

What does passive reabsorption require?

Answer 39

non-ionized form of drug

Question 40

(T/F) passive reabsorption involves energy

Answer 40

FALSE, there is no energy involved in passive reabsorption

Question 41

During passive reabsorption, what is the extent of drug ionization dependent upon?

Answer 41

pKa and urinary pH

Question 42

During passive reabsorption, urinary pH varies between _____ and _____, but can be manipulated with drugs to increase excretion of _______ or _______

Answer 42

5; 8; acids; bases

Question 43

Biliary excretion usually follows what?

Answer 43

Phase II conjugation in the liver

Question 44

What kind of transport processes are involved in biliary excretion?

Answer 44

multiple carrier-mediated transport

Question 45

(T/F) Biliary excretion requires energy

Answer 45

true

Question 46

(T/F) Biliary excretion is saturable

Answer 46

true

Question 47

(T/F) Biliary excretion is specific

Answer 47

FALSE, biliary excretion is non-specific

Question 48

What can occur during biliary excretion?

Answer 48

enterohepatic cycling

Question 49

What impairs biliary excretion?

Answer 49

liver disease

Question 50

What is pulmonary excretion important for?

Answer 50

gases and volatiles

Question 51

(T/F) Pulmonary excretion is simplified diffusion into expired aire

Answer 51

true

Question 52

During pulmonary excretion, the elimination rate is dependent upon what?

Answer 52

-respiration rate -pulmonary blood flow -solubility of the drug in blood

Question 53

_______ soluble drugs are excreted more readily

Answer 53

poorly

Question 54

(T/F) Alcohol is more soluble than nitrous oxide

Answer 54

true alcohol is very soluble, so it is not excreted well through the pulmonary system; nitrous oxide is excreted very well through the pulmonary system

Question 55

How can you increase phenobarbital excretion?

Answer 55

1. phenobarbital is a weak acid 2. ionized form is excreted; non-ionized form is reabsorbed 3. alkaline urine increases fraction of ionized form result = increased excretion; reduced reabsorption

Question 56

How can you increase amphetamine excretion?

Answer 56

1. amphetamine is a weak base 2. ionized form is excreted; non-ionized form is reabsorbed 3. acidic urine increases fraction of ionized form result = increased excretion; reduced reabsorption