Pharmacology Module 4

Front 1

5 Sites for drug metabolism

Back 1

1) Liver
2) Intestines
3) Stomach
4) Kidney
5) Intestinal bacteria

Front 2

Main site of drug metabolism

Back 2

Liver

Front 3

Main thing metabolized in the stomach

Back 3

Alcohol

Front 4

Exogenous vs endogenous

Back 4

Exogenous are things we put in our body
Endogenous are things created in our body that need metabolizing

Front 5

5 Goals of metabolism

Back 5

1) Change a drug from lipophilic to hydrophilic to be excreted
2) Inactivate a substance
3) Make a substance more active
4) Activate a prodrug
5) Increase toxicity

Front 6

First order kinetics

Back 6

Conc of drug is lower than the metabolizing capacity of the body

Front 7

What curve looks like in a first order kinetic graph

Back 7

Conc decreases steadily as time increases

Front 8

Zero order kinetics

Back 8

Conc of drug is higher than the body's metabolizing capacity

Front 9

What graph looks like in zero order kinetics

Back 9

Linear graph decreasing as time goes on

Front 10

First pass metabolism

Back 10

Amount of drugs that are metabolized before entering the circulation

Front 11

First pass metab in the stomach

Back 11

Alcohol uses alcohol dehydrogenase to create acetaldehyde

Front 12

First pass metab in the intestines

Back 12

A drug uses a CYP enzyme to make a metabolite

Front 13

First pass metab with intestinal bacteria

Back 13

A drug uses bacterial enzymes to make a metabolite

Front 14

First pass metab in the liver

Back 14

A drug uses a CYP enzyme to make a metabolite

Front 15

Extraction ratio

Back 15

Depends on how much metabolism occurs during first pass

Front 16

A high extraction ratio implies a ___ oral bioavailability and therefore requires a ___ dose than IV

Back 16

Low, higher

Front 17

High or low extraction ratio drugs are susceptible to drug-drug interactions

Back 17

High

Front 18

What phase is it when lipophilic drugs are converted to more polar molecules

Back 18

Phase 1

Front 19

What phase is it when drugs undergo oxidation, reduction, and hydrolysis

Back 19

Phase 1

Front 20

What phase of metabolism is mediated by cytochrome p450, esterase's, and dehydrogenases

Back 20

Phase 1

Front 21

What phase is it when conjugation reactions occur?

Back 21

Phase 2

Front 22

What is a conjugation reaction

Back 22

More water soluble molecules are added to the drug

Front 23

4 water soluble molecules added to the drug during conjugation

Back 23

Glucuronic acid, sulfate, acetate, or amino acids

Front 24

Metabolites generated in phase 2 metabolism are more/less active?

Back 24

Less

Front 25

What is the exception to the phase II activity rule (Drugs become less active normally)

Back 25

Morphine is metabolized to morphine 6 glucuronide, which is more potent than morphine

Front 26

Sites of phase 1 and phase 2 metabolism

Back 26

1) Smooth ER
2) Cytoplasm

Front 27

What is the exception to the locations of the phases of metabolism

Back 27

Glucuronidation occurs in the SER, not cytoplasm

Front 28

What is the largest family of drug metabolizing enzymes

Back 28

CYP

Front 29

What is the majority of drug metabolism performed by

Back 29

CYP

Front 30

Mechanism of action of CYP

Back 30

Oxidation by adding 1 O2 atom to the molecule, creating water as a by-product

Front 31

Main factor affecting CYP activity

Back 31

Nutrition

Front 32

How to name CYP 3A4

Back 32

3 - Family, A - sub-family, and 4 - isozyme

Front 33

5 types of Phase II metabolizers

Back 33

1) UGT's
2) SULTs
3) GST's
4) NAT's
5) TPMT

Front 34

UGT mechanism of action

Back 34

Located in SER
Catalyze glucuronidation
Increase polarity

Front 35

SULTs mechanism of action

Back 35

Catalyze transfer of sulfate to hydroxyl group on a drug
Increase polarity

Front 36

GST's mechanism of action

Back 36

Catalyze transfer of glutathione to drug
Lowers toxicity

Front 37

NAT's mechanism of action

Back 37

Transfers acetyl group from acetylcoA to drug
Increases water solubility

Front 38

TPMT mechanism of action

Back 38

Transfer methyl to drug

Front 39

What 2 drug metabolizers are most susceptible to genetic polymorphisms

Back 39

NAT and TPMT

Front 40

4 Factors affecting drug metabolism

Back 40

1) Age
2) Drug interactions
3) Disease state
4) Genetic polymorphisms

Front 41

When does drug metabolism become fairly strong

Back 41

2-17

Front 42

What is enzyme induction

Back 42

A cell synthesizes an enzyme in response to presence of a drug

Front 43

3 possible consequences of drug enzyme induction

Back 43

Lower plasma conc.
Decreased drug activity (Inactive metabolite)
Increased drug activity (Active metabolite)

Front 44

3 Consequences of enzyme inhibition

Back 44

1) Higher plasma conc.
2) Higher therapeutic effect
3) Higher chance of toxicity

Front 45

Disease _____ CYP activity

Back 45

Decreases

Front 46

CYP 2C9 metabolizes

Back 46

Warfarin

Front 47

Warfarin is metabolized by what enzyme

Back 47

CYP 2C9

Front 48

A SNP in CYP 2C9 would cause

Back 48

Lower enzyme activity, increased risk of bleeding

Front 49

CYP 2D6 metabolizes

Back 49

Codeine - Morphine

Front 50

Codeine is metabolized by what enzyme

Back 50

CYP 2D6

Front 51

4 Possible consequences of a CYP 2D6 SNP

Back 51

Ultra-rapid metabolizer
Extensive metabolizer
Intermediate metabolizer
Poor metabolizer

Front 52

Consequences of a UM SNP of CYP 2D6

Back 52

Ultra rapid metabolizer - Decreased plasma conc and therapeutic response

Front 53

Consequences of a EM SNP of CYP 2D6

Back 53

Extensive metabolizer - Normal CYP activity

Front 54

Consequences of a IM SNP of CYP 2D6

Back 54

Intermediate metabolizer - Decreased CYP activity - Higher therapeutic response, higher plasma conc

Front 55

Consequences of a PM SNP of CYP 2D6

Back 55

Poor metabolizer - Almost no activity - Dangerous therapeutic response, very high plasma conc

Front 56

UGT 1A1's mechanism of action

Back 56

Glucuronidates anti-cancer compound SN-38

Front 57

Anti-cancer compound SN 38 is metabolized by

Back 57

UGT 1A1

Front 58

SNP of UGT 1A1 causes

Back 58

Less enzyme activity
Diarrhea
dose limiting bone marrow suppression

Front 59

NAT2's mechanism of action

Back 59

Acetylates isoniazid (TB treatment)

Front 60

Isoniazid is used for what, and is metabolized by what

Back 60

TB , NAT2

Front 61

A rapid SNP of NAT2 will cause

Back 61

High response to isoniazid - Ineffective treatment of TB

Front 62

A slow SNP of NAT2 will cause

Back 62

Isoniazid toxicity - High cancer risk