Pharmacokinetics III

Question 1

What is the goal of bio transformation and metabolism of drugs xenobiotics?

Answer 1

Promote their elimination from the body

Question 2

What does the bio transformation of drugs convert lip soluble, non-ionized compounds to?

Answer 2

Water soluble, ionized metabolites

Question 3

If a drugs molecular weight is <350, what organ excretes it?

Answer 3

Kidney

Question 4

If a drugs molecular weight is >350, what is it excreted in?

Answer 4

Bile

Question 5

Where does most metabolism occur?

Answer 5

Liver

Question 6

What is an example of a drug that needs to be metabolized to be active? What is its active metabolite?

Answer 6

Codeine

Morphine

Question 7

What is an example of a metabolite that is more active than the parents drug?

Answer 7

Parent drug diazepam is converted to nordiazepam and then to oxazepam

Question 8

What is an example of a drug that is metabolized to toxic metabolites? What is the toxic metabolite?

Answer 8

Acetaminophen

N-acetyl-p-benzo-quinone imine

Question 9

In acetaminophen metabolism, the increased production of metabolites leads to what?

Answer 9

Oxidative stress and hepatotoxicity

Question 10

Ethanol induces acetaminophen metabolism through what?

Answer 10

CYP2E1

Question 11

What is phase 1 of bio transformation reactions?

Answer 11

Convert lip soluble , non-ionized compounds to more ionized, hydrophilic metabolites

Question 12

What is phase II of biotransformation reaction?

Answer 12

It adds an ionized, charged particle to a phase I metabolite to form a more polar and hydrophilic conjugate

Question 13

What type of phase I reactions are most common?

Answer 13

Oxidation

Question 14

Are phase I reactions compound specific?

Answer 14

There are no specific enzymes metabolizing a particular drug
Enzymes instead INTRODUCE or MASK specific functional groups or bonds of multiple drugs

Question 15

What kind of phase I enzymes are inducible ?

Answer 15

Microsomal (CYP450s)

Question 16

What is the function of CYP450s?

Answer 16

Microsomal enzymes in the liver that oxidase drugs, acting as a handle for phase II conjugation

Question 17

What P450 subtype metabolizes > 50% of drugs

Answer 17

3A4

Question 18

What is the ONLY phase II enzyme that is inducible?

Answer 18

Glucuronyl transferase

Question 19

What induces CYP1A2?

Answer 19

Smoking, chargrilled food

Question 20

What induces CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP3A4?

Answer 20

Barbiturates/phenobarbital, St John Wort

Question 21

What induces CYP2E1?

Answer 21

Ethanol

Question 22

What is an inhibitor of CYP2D6?

Answer 22

Fluoxetine (Prozac)

Question 23

What is an inhibitor of CYP3A4?

Answer 23

Grapefruit juice

Question 24

Some drug oxidation reactions are catalyzed by other enzymes rather than via CYP450s. For example, ______ is metabolized by a soluble cytoplasmic enzyme, alcohol dehydrogenase, in addition to CYP2El.

Answer 24

Ethanol

Question 25

Non-oxidative reactions such as reductive reactions add a hydrogen atom. What is an example of a drug that works in this way?

Answer 25

Warfarin. It is inactivated by conversion by CYP2A6.

Question 26

Non-oxidative reactions such as hydrolytic reactions occur in plasma in many tissues. What is an example of a drug that works in this way?

Answer 26

Esterases and amidases (Succinylcholine, local anesthetics)

Question 27

Although rare, there are some drugs that undergo phase II reactions BEFORE phase I reactions. For example, _____ is acetylated to acetylhydrazine (phase II) prior to undergoing hydrolysis (phase I). Acetylation of drugs often leads to _____.

Answer 27

Isoniazid (INH) | hepatotoxicity

Question 28

If a drug molecule has a suitable _____, either in the parent molecule or phase I metabolite, it is susceptible to conjugation

Answer 28

functional group

Question 29

The majority of Phase II conjugation reactions occur in the ___ and are mediated by ______.

Answer 29

Liver | glucuronidation and UGTs

Question 30

What are the end products of Phase II reactions?

Answer 30

Decreased lipid solubility Polar & inactive Have a larger molecular weight Readily eliminated

Question 31

Glucuronidation involves the formation of what phosphate | compound?

Answer 31

uridine diphosphate glucuronic acid (UDPGA)

Question 32

What enzyme catalyzes the transfer of glucuronic acid to the substrate forming a bond

Answer 32

UDP glucuronyl transferase (UGT)

Question 33

What is a genetic polymorphism?

Answer 33

Mutation that can lead to enzyme deficiency and altered response to drugs

Question 34

What does phase I polymorphism of CYP2D6 cause?

Answer 34

Leads to poor metabolism of codeine to morphine

Question 35

What does phase I polymorphism of aldehyde dehydrogenase deficiency cause?

Answer 35

Alcohol flush reaction

Question 36

In the GI tract, digestive or bacterial enzymes may ___ the conjugated drug which can then be reabsorbed into the bloodstream

Answer 36

free

Question 37

Excretion is enhanced by agents that:

Answer 37

1) bind drugs in the intestine (charcoal) increasing peristalsis 2) antibiotics that eliminate the GI bacteria (birth control)

Question 38

What is an example of a drug that is excreted very quickly?

Answer 38

Penicillin

Question 39

What is an example of a drug that is excreted very slowly?

Answer 39

Diazepam

Question 40

Which of the following enzymes is NOT inducible? 1. glucuronyl transferase 2. CYP2E1 3. N-acetyltransferase 4. CYP3A4 5. CYP1A2

Answer 40

N-acetyltransferase

Question 41

Enterohepatic circulation: 1. Increases half-life of a drug 2. Decreases half-life of a drug 3. Increases the clearance of a drug 4. Is not influenced by GI motility 5. happens only when toxic doses are administered

Answer 41

Increases half-life of a drug

Question 42

Which of the major elimination functions will decrease first with advancing age? 1. G.I elimination 2. renal elimination 3. phase I metabolism 4. conjugations

Answer 42

renal elimination

Question 43

First-order elimination is dependent on : 1. Plasma concentration 2. Biological system

Answer 43

Plasma concentration

Question 44

``` Lidocaine – CL = 38.4 L/hr F = 0.35; TC = 3mg/L t1/2 = 2 hrs t = 2 hrs. What is the proper maintenance dose if administered IV? 1. 30mg 2. 100mg 3. 180mg 4. 230mg 5. 300mg ```

Answer 44

230mg

Question 45

What does phase II polymorphism of fast and slow metabolizers cause?

Answer 45

Isoniazid (INH) has bi-modal distribution | "slow metabolizers" and "fast metabolizers"

Question 45

Fast and slow acetylators for Isoniazid are examples of what?

Answer 45

Phase II polymorphisms