SAS 3 Introduction to Drug Metabolism and Phase I Metabolism Reactions

Question 1

Plays a central role in the elimination of drugs and other foreign compounds (xenobiotics) from the body.

Answer 1

METABOLISM

Question 2

Most organic compounds entering the body are

Answer 2

lipophilic.

Question 3

If lipophilic drugs were not metabolized to polar, water- soluble products, they would remain

Answer 3

indefinitely in the body, eliciting their biologic effects.

Question 4

The formation of water- soluble metabolites not only enhances DRUG ELIMINATION, but also leads to compounds that are generally pharmacologically

Answer 4

INACTIVE and relatively NONTOXIC.

Question 5

Drug metabolism reactions are regarded as

Answer 5

detoxication (or detoxification) processes

Question 6

Prodrugs

Answer 6

parent compound is inactive when administered & must be metabolically converted to a biologically active drug (metabolite).

Question 7

it is now clear that not all metabolites are

Answer 7

nontoxic

Question 8

is the process of preparing foreign chemicals for removal from the body

Answer 8

Metabolism

Question 9

is usually terminated by metabolic processes

Answer 9

Drug action

Question 10

is one factor in determining the duration of drug action

Answer 10

The rate of drug metabolism

Question 11

Metabolism often occurs in two step10 s

Answer 11

Phase I (FUNCTIONALIZATION)
Phase II (CONJUGATION)

Question 12

Phase I

Answer 12

Functionalization phase

Question 13

involves chemical transformations, usually catalyzed by enzymes, including oxidations, reductions, hydrolyses, and other reactions that prepare the drug for elimination from the body.

Answer 13

Phase I metabolism

Question 14

generally found in the ER

Answer 14

Oxidative enzymes

Question 15

Hydrolytic enzymes

Answer 15

most often located in the cell cytoplasm or in plasma

Question 16

Conjugation enzymes

Answer 16

cytoplasm & ER

Question 17

PHASE 1 POLAR FUNCTIONAL GROUP

Answer 17

(OH, COOH, NH2, SH)

Question 18

Direct introduction of functional group or by modifying or _____ existing functionalities (e.g., reduction of ketones and aldehydes to alcohols; oxidation of alcohols to acids; hydrolysis of esters and amides to yield COOH, NH2,OH groups)

Answer 18

“unmasking”

Question 19

Phase I. An Analogy

Answer 19

Drug Molecule + Functional Group + More Polar than the Drug molecule

Question 20

metabolism are more polar than the drug molecule.

Answer 20

PHASE I

Question 21

Although, Phase 1 may not produce sufficiently hydrophilic or inactive metabolites, they generally tend to provide a _________ in the molecule that can undergo subsequent Phase II reactions.

Answer 21

functional group or “handle”

Question 22

to attach small, polar, and ionizable endogenous compounds such as glucuronic acid, sulfate, glycine and other amino acids to the functional handles of Phase I metabolites to form WATER- SOLUBLE CONJUGATED PRODUCTS.

Answer 22

Phase II

Question 23

Phase II. An Analogy

Answer 23

More polar than the drug molecule + small, polar, and ionizable endogenous compounds such as glucuronic acid, sulfate, glycine and other amino acids = WATER- SOLUBLE CONJUGATED
PRODUCTS

Question 24

Complement one another in detoxifying and facilitating the elimination of drugs and xenobiotics.

Answer 24

Phase I and Phase II reactions

Question 25

• most important organ in drug metabolism.
• Rich in almost all of the drug- metabolizing enzymes

Answer 25

Liver

Question 26

A well- perfused organ and plays a paramount role in the detoxification and metabolism of endogenous and exogenous compounds in the bloodstream.

Answer 26

Liver

Question 27

Drugs administered orally and are absorbed through the GI tract must first pass through the LIVER (therefore, they are susceptible to hepatic metabolism—__________ ) before reaching the systemic circulation

Answer 27

first- pass effect

Question 28

Examples of drugs undergoing first- pass effect

Answer 28

Salicylamide
Lidocaine
Isoproterenol
Meperidine
Pentazocine
Propoxyphene
Propranolol
Morphine
Nitroglycerine

Question 29

Reaction requires both molecular oxygen and the reducing agent NADPH (nicotinamide adenine dinucleotide phosphate).

Answer 29

OXIDATIVE BIOTRANSFORMATION PROCESSES

Question 30

Most common and important in drug metabolism

Answer 30

RH + NADPH + O2 + H+ —->ROH + NADP+ + H2O

Question 31

Most common and important in drug metabolism

Answer 31

RH + NADPH + O2 + H+ —->ROH + NADP+ + H2O