Drug Metabolism, Pharmacogenetics, And Therapeutic Choice

Question 1

The first major route in which drugs are eliminated from the body is

Answer 1

Excretion through the Kidney (unchanged)

Question 2

Plays a pivotal role in terminating the biological activity of some drugs, particularly those that have small molecular sizes or possess polar characteristics

Answer 2

Renal excretion

Question 3

A property of most drugs that facilitates passage through biological membranes as well as access to sites of action is that most drugs are

Answer 3

Lipophilic

Question 4

Renal excretion of lipophilic compounds is

Answer 4

Poor

Question 5

The 2nd major route of drug elimination from the body is

Answer 5

Biotransformation of Drugs or Xenobiotics into more hydrophilic metabolites

Question 6

Biotransformation of drugs to polar and hence more readily excretable products

Answer 6

Drug Metabolism

Question 7

Alters the pharmacodynamic and pharmacokinetic properties of a drug, as well as the toxic properties

Answer 7

Drug Metabolism

Question 8

Typically increases clearance and shortens half-lives to significant extents

Answer 8

Drug Metabolism

Question 9

For example, the half-lives of lipophilic barbiturates (e.g., pentobarbital) would be extremely long if it were not for their metabolic conversion to

Answer 9

Water soluble compounds

Question 10

Usually detoxifies, although some metabolic products have enhanced toxicity relative to the parent drug

Answer 10

Drug Metabolism

Question 11

Most metabolic reactions occur at some point between absorption of the drug into the general circulation and its

Answer 11

Renal Elimination

Question 12

In general, all of these chemical reactions can be assigned to one of two major categories, termed

Answer 12

Phase I and Phase II reactions

Question 13

Introduce or expose a polar functional group (e.g., OH, COOH, NH2, or SH) on the parent compound

Answer 13

Phase I reactions

Question 14

Typically involve the conjugation of endogenous compounds (e.g., glucuronic acid or glutathione) to phase I products to yield highly polar (but chemically inactive) conjugates

Answer 14

Phase II (Conjugation) Reactions

Question 15

The principle organ of drug metabolic activity

Answer 15

Liver

Question 16

Following oral administration, drugs are first transported via the portal system to the

Answer 16

Liver

Question 17

This limits the oral bioavailability of highly metabolized

Answer 17

Drugs

Question 18

In the GI tract, drugs may be metabolized by microorganisms, digestive enzymes, and

Answer 18

Gastric fluids

Question 19

Major enzymatic system for Phase I functionalization (oxidative) reactions

Answer 19

Cytochrome P450 system

Question 20

Promiscuous enzymes, with low substrate specificity

Answer 20

CYPs

Question 21

The only common structural feature of the wide variety of drugs and chemicals that serve as substrates in the P450 system

Answer 21

High lipid solubility

Question 22

For the CYPs, distinct gene families are designated by

Answer 22

Arabic numerals, ex: CYP3

Question 23

Subfamilies are then designated by

Answer 23

Capital letters. Ex: CYP3A

Question 24

Then individual genes are designated by a

Answer 24

Number. Ex: CYP3A4

Question 25

These six enzymes are responsible for the bulk of the drug and xenobiotic metabolism in the liver

Answer 25

CYP3A4, 2C9, 1A2, 2E1, 2D6, and 2C19

Question 26

Accounts for the metabolism of >50% of the clinically prescribed drugs that undergo hepatic metabolism

Answer 26

CYP3A4

Question 27

Catalyze the coupling of an activated endogenous substance with an exogenous agent (e.g., a drug) or another endogenous compound

Answer 27

Transferases

Question 28

Conjugation reactions require

Answer 28

Transferases

Question 29

What are the 5 conjugation reactions?

Answer 29

Glucuronidation, N-Acetylation, Glutathione conjugation, Sulfation, and Methylation

Question 30

Is quantitatively the most important conjugation reaction

Answer 30

Glucuronidation

Question 31

What is the enzyme for glucuronidation?

Answer 31

UDP-glucuronosyltransferase (UGT)

Question 32

Conjugation of reactive electrophilic compounds with the tripeptide glutathione (GSH)

-A major detoxification pathway for drugs and carcinogens

Answer 32

Glutathione conjugation

Question 33

What is the enzyme for Glutathione conjugation?

Answer 33

glutathione-S-transferase (GST)

Question 34

Drug metabolism reactions often occur sequentially (i.e., Phase I → Phase II). An exception to this is

Answer 34

Isoniazid (INH)

Question 35

Genetic factors contribute to large inter-individual differences in

Answer 35

Metabolic Rate

Question 36

What is the underlying mechanism for slower acetylators?

Answer 36

Polymorphism of NAT2 (N-Acetyltransferase 2) Gene

Question 37

Inhibits CYP3A4 and decreases metabolism rates of some drugs

Answer 37

Grapefruit Juice

Question 38

Exposure to drugs or xenobiotics can induce

Answer 38

Metabolizing enzymes

Question 39

Many inducers of CYPs also induce enzymes involved in

Answer 39

Phase II reactions

Question 40

Acute and chronic diseases that affect liver function or architecture markedly diminish

Answer 40

Drug metabolism

Question 41

Can limit blood flow to the liver and impair the disposition of drugs (e.g., morphine and lidocaine) whose metabolism is flow-limited

Answer 41

Cardiac Disease

Question 42

Can impair hepatic drug metabolism by impairing the activity or causing defective formation of metabolic enzymes

Answer 42

Heavy metal poisoning and Porphyria