ADME 2

Question 1

What is biotransformation?

Answer 1

The conversion of one molecule to another via enzymatic process.

Question 2

Most drugs that are part of Phase 1 or Phase 2 metabolism are modified when?

Answer 2

Prior to excretion by enzymatic reactions.

Question 3

Enzymes involved in biotransformation are often involved metabolizing ___________ drug classes

Answer 3

Multiple

Question 4

If the same enzyme is utilized in processing two drugs given simultaneously they can ________?

Answer 4

Produce drug interaction due to changes in metabolism rates.

Question 5

Phase 1 metabolism involves?

Answer 5

Oxidation, re-education and hydrolysis which unmasks or inserts a more polar functional group.

Question 6

Phase 2 metabolism involves?

Answer 6

reactions which add functional groups to alter the polarity of the molecule.

Question 7

Examples of reactions for phase 2 metabolism

Answer 7

glucuronidation, methylation, sulphation and acetylation.

Question 8

Enzymes mediating the reaction in phase 2 metabolism are called

Answer 8

Transferases

Question 9

The goal of Phase 1 and 2 metabolism

Answer 9

is to produce more polar, hydrophilic molecules that can be excreted.

Question 10

Most important enzymes in Phase 1 metabolism

Answer 10

is actually a group of similar enzymes classified as cytochrome P450 enzymes (CYP enzymes)

Question 11

P450 or CYP enzymes are?

Answer 11

Oxidase that act to detoxify many organic compounds

Question 12

CYP and p450 enzymes are _____ selectivity hence many drugs are modified by CYP.

Answer 12

Low

Question 13

Other enzymes included for phase 1 metabolism

Answer 13

enzymes include the Flavin containing mono-oxegenases (FMOs) or hydrolytic enzymes such as epoxide hydrolases

Question 14

Phase 2 has ________ enzymes

Answer 14

Conjugation

Question 15

Key enzymes for phase 2 are?

Answer 15

Key enzymes are the uridine diphosphoglucuronosyltransferases, Sulfotransferases, Methyl transferases and N-acetyltransferases

Question 16

Enzymes in phase 2 mediate what?

Answer 16

glucuronidation, suflation, methylation and N-acetylation respectively.

Question 17

What are the primary routes of drug elimination?

Answer 17

Renal and Biliary

Question 18

What are the factors that alter the ability for the drug to be eliminated by renal excretion?

Answer 18

include physiochemical properties such as molecular weight and hydrophilicity, Renal blood flow, binding of drug to other molecules such as plasma proteins and renal function.

Question 19

Physiochemical properties are often altered by

Answer 19

Phase 1 and 2 metabolism

Question 20

Renal blood flow can be altered by other ________

Answer 20

Medications

Question 21

Poor renal function can produce poor elimination rates in some patients

True or false

Answer 21

True

Question 22

Secondary routes of elimination include

Answer 22

exhalation or coughing (lungs), Saliva, Seat, Milk and Tears.

Question 23

Cyp enzymes are found in

Answer 23

the ER and ER derived components of the cell (microsomes).

Question 24

Why are CYP enzymes so important?

Answer 24

They are extremely important to drug metabolism since they are very non-selective but efficient oxidizers of organic compounds

Question 25

drugs given simultaneously can compete with the same CYP catalytic sites and alter the pharmacokinetics of the drugs. This can lead to lethal drug/drug interactions, particularly for low therapeutic index drugs

True or false

Answer 25

True

Question 26

Other factors that affect expression of CYP enzymes such as _________________________________________ can also impact metabolism and thus circulating drug concentrations.

Answer 26

age and other health conditions (ex: inflammation, kidney disease)

Question 27

Drugs that are not efficiently eliminated can reach?

Answer 27

Toxic concentrations

Question 28

Elimination of drugs from the body is directly related to their

Answer 28

efficiency of elimination from the body and their exposure to Phase 1 and Phase 2 reactions

Question 29

Drugs that are rapidly biotransformed will be eliminated rapidly

Answer 29

thus reducing their half lives in circulation

Question 30

Drugs that are slowly transformed will be

Answer 30

Eliminated more slowly

Question 31

If two drugs compete for the same enzymes, such as CYP450,

Answer 31

they can dramatically alter each other’s pharmacokinetics

The drugs will be biotransformed more slowly thus increasing the circulating concentration and prolonging their time in the body.

If the drugs are taken at the normal dose, this would result in excessively high drug dosages, increasing the likelihood of adverse effects. This is an example of one type of drug interaction

Question 32

Clearance is

Answer 32

the rate of drug elimination from the body

Question 33

Renal clearance refers to

Answer 33

excretion through the kidney

Question 34

hepatic clearance refers to excretion in the

Answer 34

bile (biliary).

Question 35

Biliary clearance eliminates drugs through

Answer 35

excretion of the bile into the digestive track

Question 36

Lung clearance indicates drugs are eliminated by

Answer 36

exhalation or by mucociliary mechanisms.

Question 37

Most drugs under 500 MW that are hydrophilic are eliminated rapidly and

Answer 37

have high renal clearance.