Week 2

Question 1

Possible consequences of biotransformation (metabolism)
Activity
Polarity
Toxicity

Answer 1

Dec in activity (detoxication)
Inc in polarity
Inc in activity or bioactivation (prodrug)
Inc in toxicity (toxication)

Question 2

Metabolism (biotransformation) phase 1 and phase 2

Answer 2

Phase 1: oxidation, hydrolysis, reductive
adds or exposes function group
Phase II: conjugative- inc size and hydrophilicity
Goal: drug turned into an inactive, polar, water-soluble, and excretable metabolite

Question 3

Which organs are responsible for eliminating drugs from the body?

Answer 3

Liver and kidneys

Question 4

Which organ is responsible for metabolism of a drug?

Answer 4

Liver

Question 5

Which organ is responsible for elimination of drugs?

Answer 5

Kidney

Question 6

Cytochrome P450

Answer 6

Major enzyme for reduction/oxidation rxns during phase 1 of metabolism
Primarily found in endoplasmic reticulum (ER) of cell, small amounts in mitochondria
Utilizes NADPH and molecular oxygen

Question 7

What do phase II enzymes do?

Answer 7

Inc hydrophilicity, water solubility
Promotes excretion
Typically faster rxns than phase I

Question 8

Competitive inhibition

Answer 8

Inhibitor binds to same site on the enzyme as the substrate

Question 9

Non-competitive inhibition

Answer 9

Inhibitor binds to both enzymes at a different site than the substrate

Question 10

Uncompetitive inhibition

Answer 10

Inhibitor binds to the enzyme-substrate complex. Does not bind to active site

Question 11

Irreversible inhibitor

Answer 11

Inhibitor binds chemically with residues and destroys the enzyme

Question 12

How is felodipine impacted by grapefruit juice?

Answer 12

Grapefruit increases body absorption of felodipine into the blood by inhibiting intestinal CYP3A4 protein

Question 13

Pharmacogenomics

Answer 13

Study of how genes affect a person’s response to drugs

Question 14

Pharmacogenetics

Answer 14

Effect of genetic variation on drug response- such as safety, tolerability and efficacy

Question 15

Human genome

Answer 15

Contains 3 bill base pairs
Gene size can be from 3000 to 2.4 mill bases
30,000 approx genes code for proteins

Question 16

Polymorphism

Answer 16

Single nucleotide polymorphisms (SNPs) most common genetic variation which occurs from a diff in a single DNA building block (nucleotide)
SNPs occur q300 nucleotides on average

Question 17

Genetic mutation

Answer 17

Permanent alteration in DNA sequence, can be hereditary or acquired

Question 18

Chromosome mutations: deletion

Answer 18

When part of a chromosome is left out

Question 19

Chromosome mutations: insertion

Answer 19

Part of a chromatid breaks off and attaches to sister chromatid- results in duplic. Of genes on same chromosome

Question 20

Chromosome mutations: inversion

Answer 20

Part of chromosome breaks off and reattaches backwards

Question 21

Chromosome mutations: translocation

Answer 21

Part of one chromosome breaks off and is added to a diff chromosome

Question 22

Clinical importance of polymorphism

Answer 22

Mutation leads to alteration in AA seq of protein

If proteins are metabolic enzymes that can lead to alteration in PK and cause adverse drug rxns

Question 23

How does polymorphism effect drug metabolism? (Assume same diagnosis, same prescription and how it effects patients differently)

Answer 23

Mutations in enzymatic proteins can cause major complications

• Drug can become toxic but not beneficial due to mutation causing enzyme to convert drug to quickly to byproduct
• Drug can be not toxic and beneficial
• Drug can be not toxic and not beneficial- mutation prevents body from metabolizing drug
• Drug can be toxic but beneficial

Question 24

distribution

Answer 24

reversible xfer of drug to and from site of measurement (usually blood)

Question 25

how many liters makes up total body water "plasma+interstitial volume+intracellular volume

Answer 25

42 liters

Question 26

liters make up intracellular volume

Answer 26

28 liters

Question 27

liters make up extracellular volume

Answer 27

14 liters

Question 28

extracellular volume is consisting of what two components? how many liters?

Answer 28

interstitial volume and plasma volume. 14 liters

Question 29

liters make up interstitial volume

Answer 29

10 liters

Question 30

liters make up plasma volume

Answer 30

4 liters

Question 31

volume of distribution equation

Answer 31

volume of distribution= amount of drug administered (dose) / initial drug concentration

Question 32

define volume of distribution (Vd)

Answer 32

apparent volume into which a drug distributes in the body at equilibrium

Question 33

if the Vd volume is ~18L...

Answer 33

drug distribution is prob limited to extracellular fluid

Question 34

if the Vd volume is ~42L...

Answer 34

drug distribution is prob limited to all body water

Question 35

if the Vd volume is less than or equal to 5L...

Answer 35

drug distribution is prob limited to plasma

Question 36

if the Vd volume is greater than or equal to 42L...

Answer 36

drug distribution is into the tissue outside of plasma and interstitial fluid

Question 37

Cp is?

Answer 37

drug blood plasma concentration, used to calculate VD

Question 38

if Vd is high

Answer 38

there is low drug blood plasma (Cp) concentration which means more drug is in tissues

Question 39

if Vd is low

Answer 39

there is higher drug blood plasma (Cp) concentration which means less drug is in tissues

Question 40

two main plasma proteins that bind drugs?

Answer 40

albumin-binds to acidic drugs and few basic drugs | beta-globulin and an alpha1 acid glycoprotein also bind certain basic drugs

Question 41

What percentage of the genetic makeup in the human body is made up of our microbiome?

Answer 41

99%

Question 42

What are the microbiota organs

Answer 42

``` Gut (primary location) Oral Lungs Vagina Skin ```

Question 43

Which part of body would you find the highest microbial density?

Answer 43

large intestine (Colon)

Question 44

Stomach and small intestine have many or few species of bacteria present?

Answer 44

Few

Question 45

Gut microbiota and their role in metabolizing drugs

Answer 45

Considered “metabolic organ” Has a huge capacity to dominate and metabolize drugs Varies in patients Differences can effect drug metabolism and toxicity

Question 46

Indirect and direct interactions of microbiome and drug interaction

Answer 46

Indirect: competition between microbiome and drug (microbiota can metabolize same drug as host enzyme) Direct: partial or complete biochemical xformation of drug by microbiome-derived enzymes. Effects body metabolization of drug and drug ability to work

Question 47

Drug excretion occurs primarily In which organ?

Answer 47

Kidney-> Nephron

Question 48

what does the Nephron do?

Answer 48

Filters blood

Question 49

Nephron turns ____________ form of drug into the more hydrophilic ______ form

Answer 49

Ionized, unionized**

Question 50

Most drugs are freely filtered at the?

Answer 50

Glomerulus

Question 51

Does filtration require a drug to be “free”

Answer 51

Yes

Question 52

Passive reabsorption is favored for ________ drugs

Answer 52

Unionized

Question 53

Probenecid

Answer 53

Prevents renal clearance of penicillin and incr circulation time in blood stream

Question 54

What is Clearance (Clp)

Answer 54

Describes removal of drug from a volume of plasma in a specific time Does not indicate amount of drug removed, but the volume of plasma from which drug is removed in a time period

Question 55

T/F total drug clearance is defined as excretion from just the kidneys

Answer 55

False

Question 56

T/F clearance is defined as amount of drug removed in a given period of time from body

Answer 56

False

Question 57

T/F clearance is defines as volume of plasma from which all drug is removed in a given time period

Answer 57

True

Question 58

T/F the 1/2 life is not a pharmacokinetic parameter that can be used to measure clearance

Answer 58

False

Question 59

Half-life of drug

Answer 59

Time where half of drug is removed