Drug Metabolism

Question 1

Drug metabolism/Biotransformation is the __________ modification of drugs in the body which transforms relatively _________ agents into produce more ______, hydrophilic products which can easily be excreted.

Answer 1

Chemical
Lipophilic
Polar

Question 2

What is the main pathway to remove drugs from the body

Answer 2

Drug metabolism

Question 3

Examples of drugs that are activated by metabolism is

Answer 3

Enalapril to enalaprilat

Codeine to morphine

Question 4

What are the 3 outcomes of drug metabolism

Answer 4

Active metabolite
Active drug
Inactivation

Question 5

Drugs are mainly __________ and are easily transported across the cell membrane into the cells where they undergo biotransformation.

Answer 5

Lipophilic

Question 6

Common sites of metabolism are

Answer 6

LIVER
lungs
Kidney
Git
Skin

Question 7

Drug metabolism occurs in almost all organs of the body T/F

Answer 7

True

Question 8

Drug metabolism involves 2 types of enzymes these are

Answer 8

Microsomal
Non microsomal

Question 9

Drug metabolism is categorized MAINLY into 2 main reactions

Answer 9

Phase 1
Phase 2

Question 10

Must phase 1 occurs before phase 2

Answer 10

No

Question 11

Phase 3 rxns have been described what is it mainly involved in

Answer 11

the removal of drugs that have undergone phase 1 and or 2 reactions by transporters (P-glycoprotein)

Question 12

Phase 1 rxns are also known as ________ &__________

Answer 12

Functionalization rxns
Synthetic rxns

Question 13

Phase 1 rxns convert parent compound into a more polar (=hydrophilic) metabolite by

Answer 13

adding or unmasking functional groups

Question 14

These functional groups include

Answer 14

-OH
-SH
-NH2
-COOH

Question 15

5 types of phase 1 rxns

Answer 15

Oxidation
Reduction
Hydrolytic rxn
Cyclization
Decyclization

Question 16

Phase 2 rxn is __________ with __________ substrate to FURTHER __________aqueous __________

Answer 16

Conjugation
Endogenous
Increase
Solubility

Question 17

The endogenous substrates of phase 2 include

GAGAS

Answer 17

glucoronide
sulfate
acetate
amino acid
glycine

Question 18

What is the true detoxification step in metabolism

Answer 18

Phase 2

Question 19

Microsomal enzymes are located on what cellular organelle? And in what organs

Answer 19

Smooth endoplasmic reticulum

In Liver,
Kidney
Lungs
Intestinal mucosa

Question 20

Examples of microsomal enzymes are

Answer 20

Monooxygynases

Cytochrome P450

UGT (Uridine 5’-diphospho-glucuronosyltransferas)

Epoxide hydroxylases

Question 21

Microsomal enzymes are only involved in Phase 2 rxns
T/F

Answer 21

False
Phase 1&2

Question 22

Non Microsomal enzymes are found in

Answer 22

Cytoplasm
Mitochondria
Plasma

Question 23

Examples of non Microsomal enzymes are

Answer 23

Esterases
Amidases

Question 24

Microsomal cytochrome P450 monooxygenase family of enzymes, which ________ drugs

Answer 24

Oxidize

Question 25

Characteristics of cytochrome p450

Answer 25

Act on structurally unrelated drugs Metabolize the widest range of drugs membrane-bound, heme-containing protein.

Question 26

The human CYP family consists of ____ genes, with ____ families and ___ subfamilies.

Answer 26

57 18 44

Question 27

CYP3A4 3: A: 4:

Answer 27

Family Subfamily Gene

Question 28

Modufication of CYP ACTION can occur in 3 ways

Answer 28

• Induction of drug metabolizing enzymes • Inhibition of drug metabolizing enzymes • Biological Factors

Question 29

Biological factors include

Answer 29

Species/Strain differences - fast acetylators vs slow acetylators Disease state Sex differences(M F ) Circadian rhythm Age Diet Pregnancy Inter specie and intra specie differences – rats/mice versus humans •Genetic differences – (fast metabolizing – depolarizing muscle blockers, fast acetylators vs slow acetylators )

Question 30

Testosterone an enzyme inducer t/f

Answer 30

T

Question 31

Inhibition of CYP enzymes causes 3

Answer 31

- Decreased degradation of co-medicated drugs Increased drug plasma concentrations Risk of severe adverse events.

Question 32

Examples of inhibitors

Answer 32

cimetidine, Isoniazid, MAO Inhibitor (Phenelzine) Grapefruit juice

Question 33

Induction of CYP enzymes causes

Answer 33

Increased degradation of co-medicated drugs Decreased drug plasma concentrations Loss of pharmacological effect Risk of therapeutic failure.

Question 34

Examples of cyp inducers are

Answer 34

barbiturates, carbamazepine, rifampicin, cyclophosphamide St John wort Glucocorticoids

Question 35

Gray baby syndrome is And the deficient enzyme is

Answer 35

an adverse reaction to chloramphenicol The UDP-glucuronyl transferase enzyme system in infants, (especially premature infants, is not fully developed and incapable of metabolizing the excessive drug load needed to excrete chloramphenicol)

Question 36

Testosterone induces the drug metabolizing system T/F

Answer 36

T

Question 37

First pass effect aka

Answer 37

Presystemic metabolism

Question 38

First pass is the metabolism of drug during its passage from _______________ into _____________ _________ and it occurs with _______, ______ & _______administration

Answer 38

Absorption site Systemic circulation Oral drugs, skin, lungs

Question 39

In the GIT drugs are metabolized by __________________ & ______

Answer 39

the intestinal and gut wall enzymes liver

Question 40

Drugs given __________ bypasses the first pass metabolism

Answer 40

Intravenously

Question 41

First pass effect is a determinant of

Answer 41

Bioavailability

Question 42

4 drugs with extensive first pass effect LMNP

Answer 42

Lidocaine Nitroglycerin Propranolol Morphine

Question 43

To combat first pass drugs are given ___________ or ________

Answer 43

as high oral dose via other routes of administration

Question 44

Other factors may also affect first pass effect are 3

Answer 44

•- increased bioavailability in liver disease •- effects of other drugs •- individual variation in oral drug absorption

Question 45

Phase 1 drug and enzyme enzyme is

Answer 45

Alcohol Cytochrome p450 oxidase Dehydrogenase

Question 46

Reduction drug& enzymes

Answer 46

Eg Levodopa Cytochrome p450 reductase Decarboxylase

Question 47

Hydrolysis drug and example

Answer 47

Lidocaine : local anesthetic agents Esterase Amidase

Question 48

What do we add in phase 1

Answer 48

Functional group

Question 49

What do we add in phase 2

Answer 49

Endogenous substance

Question 50

Glucoronidation Acetylation Sulphation Glycine conjugation Methylation Gluthathione conjugation

Answer 50

Glucoronide Acetate Sulphate Glycine Methyl group Gluthatione