Drug Metabolism

Question 1

Drug metabolism aka _______ is the chemical modification of drugs in the body which transforms ______ into produce more ____, ____ which can easily be excreted.

Answer 1

Bio transformation
Relatively lipophilic agents
Polar, hydrophilic products

Question 2

Drug metabolism involves chemical activation of inactive drugs to their active substrates eg
____ to ____
______ to _____

Answer 2

Enalapril to enalaprilat
Codeine to morphine

Question 3

Outcome of drug metabolism:
______
______
______

Answer 3

Inactivation
Active metabolite
Active drug

Question 4

Drugs are mainly _____

Answer 4

Lipophilic

Question 5

Drug metabolism occurs mainly in the ___, and involves both ____ and ___ enzymes.

Answer 5

LIVER
Microsomal and non-microsomal enzymes

Question 6

Drug metabolism occurs in almost all organs of the body and other relatively common sites are

Mnemonic: Let’S Get Kids(sounds like let’s get this) Hint: 4 sites

Answer 6

Lungs
Kidney
Skin
GIT

Question 7

Drug metabolism is categorized mainly into ___ main reactions, namely:

Answer 7

Two
Phase I metabolism
Phase II metabolism

Question 8

Phase 3 reaction involves removal of drugs that have undergone phase 1 and or 2 reactions by transporters called _____

Answer 8

P-glycoprotein

Question 9

Phase I reactions are also knows as ____/_____ reactions

Answer 9

Functionalization
Non-synthetic

Question 10

Phase I reactions convey a parent compound into a ____ metabolite by _______

Answer 10

More polar hydrophilic
Adding/unmasking functional groups

Question 11

Phase I reactions include:

Answer 11

Oxidative
Reductive
Hydrolytic
Cyclization
Decyclization

Question 12

After phase I reactions, drugs must go through phase 2 to be sufficiently polar to be excreted readily. (True/False)

Answer 12

False, after phase I reactions, drugs may be sufficiently polar to be excreted readily

Question 13

Phase 2 reactions involve conjugation with _____ to further increase aqueous solubility.

Answer 13

Endogenous substrates

Question 14

Phase 2 reactions include:

Mnemonic: SAGGA

Answer 14

Glucuronide
Sulfate
Acetate
Amino acid
Glycine

Question 15

Phase 2 is referred to as the ______ step in the metabolism process.

Answer 15

True detoxification step because the drug is more likely to be excreted.

Question 16

Microsomal enzymes are located on the ______ in what organs?
Mnemonic: KILL

Answer 16

Smooth Endoplasmic Reticulum
Liver, kidney, lungs, intestinal mucosa.

Question 17

Examples of microsomal enzymes:

Answer 17

Monooxygenases
Cytochrome P450
UGT- UDP glucuronosyltransferase enzyme
Epoxide hydroxylases

Question 18

Microsomal reactions are involved in phase I and II reactions. (True/False)

Answer 18

True

Question 19

Non-microsomal enzymes are found in _____, ____ and _____ . Examples are:

Answer 19

•Cytoplasm
Mitochondria
Plasma
•Esterases , amidases

Question 20

______ metabolize the widest range of drugs and also act on structurally unrelated drugs.

Answer 20

Microsomal cytochrome P450 monooxygenases family of enzymes

Question 21

Cytochrome P450 system involves enzymes that are ______ and _____

Answer 21

Membrane bound
Heme-containing protein

Question 22

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

Answer 22

57
18
44

Question 23

CYP____ is involved in a significantly higher number of drug metabolism compared to other enzymes.

Answer 23

CYP3A4

Question 24

Example of enzymes in category of human CYP family include:

Answer 24

CYP2D6
CYP2C19
CYP2C9
CYP3A4
CYP3A5

Question 25

The cytochrome P450 system enzymes are named based on ____.

Answer 25

The family

Question 26

In CYP3A4: 3 stands for A stands for 4 stands for

Answer 26

3-Family A-Subfamily 4-Gene number

Question 27

Biological factors affecting drug metabolism: (7 in number)

Answer 27

Species/Strain differences (fast acetylators vs slow acetylators) Disease state Sex differences Circadian Rhythm Age Diet Pregnancy

Question 28

Modification of drug metabolism involves:

Answer 28

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

Question 29

Effects of inhibition of CYP enzymes:

Answer 29

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

Question 30

Examples of CYP enzyme inhibitors:

Answer 30

Cimetidine Isoniazid Monoamine oxidase inhibitor-Phenelzine

Question 31

Effects of induction of CYP enzymes:

Answer 31

Increased degradation of co-medicated drugs Decreased drug plasma concentrations Loss of pharmalogical effects Risk of therapeutic failure

Question 32

Examples of CYP enzymes inducers:

Answer 32

Barbiturates Carbamazepine Rifampicin Cyclophosphamide

Question 33

Testosterone is an enzyme ___

Answer 33

Inducer

Question 34

Grape juice inhibits _____

Answer 34

Felodipine

Question 35

In pregnancy, there is _____ level of hormone inducer or inhibitors.

Answer 35

Increased

Question 36

Progesterone is an enzyme ____

Answer 36

Inducer

Question 37

Pertaining to pregnancy, _____ contains metabolizing enzymes

Answer 37

Placenta

Question 38

Drugs with extensive first pass effect include: (Hint: LMNP)

Answer 38

Lidocaine Propranolol Nitroglycerin Morphine

Question 39

Factors affecting first pass effect:

Answer 39

Increased bioavailability in liver disease Effects of other drugs Individual variation in oral drug absorption