Mouse Blue Book Vol I - Chp 16

Front 1

In vivo refers to studies carried out in:

Back 1

a. Whole multicellular organisms
b. Whole cells or tissues
c. In test tubes
d. Cell-free systems

Hint 1

a. latin - "In Life"

Front 2

An investigator performs a drug perfusion study on an excised pig heart, what type of study is this?

Back 2

a. In vivo
b. In vitro
c. Ex vivo
d. Ez vivo

Hint 2

c.
Ex vivo

Front 3

Pharmacodynamics (PD) refers to:

Back 3

a. To what the body does to a drug or other chemical
b. To what a drug or any given bioactive chemical substance does to the body
c. To the study of how drugs interact with the total gene expression
d. None of the above

Hint 3

b.
To what a drug or any given bioactive chemical substance does to the body

Front 4

Pharmacokinetics (PK) refer to:

Back 4

a. To what the body does to a drug or other chemical
b. To what a drug or any given bioactive chemical substance does to the body
c. To the study of how drugs interact with the total gene expression output of the genome
d. None

Hint 4

a.
what the body does to a drug or other chemical

Front 5

Which of the following is the correct description of PK processes?

Back 5

a. Absorption, signaling pathway, metabolism, excretion
b. Absorption, distribution, transcriptional responses, excretion
c. Genomic responses, distribution, metabolism, excretion
d. Absorption, distribution, metabolism, excretion

Hint 5

d (ADME)

Front 6

The coupled action of PK and PD results in which of the following in the organism?

Back 6

a. A therapeutic response
b. A therapeutic failure
c. Unwanted toxicity
d. All of the above
e. A and c only

Hint 6

d.
All of the above

Front 7

Which of the following may result in a lack of effective plasma concentration of a drug?

Back 7

a. Dose is too low
b. Dosing interval is too long
c. Low bioavailability
d. Quickly excreted
e. All of the above

Hint 7

e.
All of the above

Front 8

Pharmacogenomics refer to:

Back 8

a. To what the body does to a drug or other chemical
b. The study of how variations in the animal genome affect the response to medications.
c. None of the above

Hint 8

b.
The study of how variations in the animal genome affect the response to medications.

Front 9

Trp 53 (+/-) mouse is a model for

Back 9

a. Immunotoxicity studies
b. Tumor suppressor-gene model
c. Diabetes mellitus type II
d. Study muscle growth

Hint 9

b.
Tumor suppressor-gene model

Front 10

Which is UNTRUE about microarray test?

Back 10

a. Microarray is testing of a cell sample to find out what genes are expressed and what genes are not expressed in that sample
b. Monitoring expression levels of thousands of genes simultaneously
c. The isolated mRNA from animals are reversed transcribed to produce fluorescence-tagged cDNA
d. The fluorescence-tagged cDNA allowed to hybridized to oligomers (25-70) bases long that are bound to the platform (gene chip)
e. Gene chip is a collection of spots, commonly representing multiple genes at each spot

Hint 10

e, single gene / spot

Front 11

What is the UNTRUE about classical approach of the drug discovery?

Back 11

a. It is phenotype-driven approach
b. No prior knowledge about the nature of the drug target is needed
c. This approach requires some prior knowledge about biological target
d. It is empirical and completely random process

Hint 11

c.
This approach requires some prior knowledge about biological target

Front 12

Which of the following tools can be used to search for a new drug target in Modern approach?

Back 12

a. Gene-expression microarray
b. Transgenic or knockout mice
c. A only
d. A and B

Hint 12

d
A and B

Front 13

Chemogenomics can be defined as a genomic response to chemical compounds. It is based on the concept that bioactive compounds can act as mimics of genetic mutation. Inactivation of a specific protein by a drug is conceptually equivalent to mutation perturbation of the corresponding gene.

Back 13

True or False:

Hint 13

True

Front 14

A Target is:
a set of molecules in the body that may be addressed by drugs to produce a therapeutic effect.

Back 14

True or False:

Hint 14

True

Front 15

Target validation involves demonstrating that a molecular target is critically involved in a disease process, and that modulation of the target is likely to have a therapeutic effect. A validated target is considered druggable.

Back 15

True or False:

Hint 15

True

Front 16

Dystrophin-deficient mouse (MDX) are model for

Back 16

a. Dwarfism
b. Obesity
c. Duchene muscular dystrophy
d. Type II diabetes mellitus

Hint 16

c
Duchene muscular dystrophy

Front 17

RNA interference (RNAi) is used for

Back 17

a. Translation of a desired therapeutic protein
b. As agonists
c. To suppress gene expression
d. none of the above

Hint 17

c
To suppress gene expression

Front 18

Leptin-deficient mice (ob/ob) are model for

Back 18

a. Dwarfism
b. Tumor chemotherapy
c. Obesity and diabetes type-2
d. Muscular dystrophy

Hint 18

c
Obesity and diabetes type-2

Front 19

Transgenic mice, which is UNTRUE?

Back 19

a. Overexpression of the inserted gene
b. Functional equivalent of induction of gene product
c. Functional equivalent of activation of gene product
d. Functional equivalent of blockade of gene product

Hint 19

d
Functional equivalent of blockade of gene product

Front 20

Analysis of the genotype produced in the genetically altered mouse is the key success of target validation

Back 20

true or false

Hint 20

False -> Phenotype is

Front 21

Which of the following target validation IS NOT carried out in vivo studies?

Back 21

a. Histology
b. Inflammatory response
c. Binding assay against the drug target
d. Blood chemistry

Hint 21

c. binding assay

Front 22

In Phenotype driven approach which is true

Back 22

a. Knockout mouse with random mutation is generated
b. The phenotypes of the KO evaluated
c. The altered genes are identified as drug targets
d. Screening of compound libraries against this drug target
e. All of the above

Hint 22

e.
All of the above

Front 23

In preclinical studies which strains of mice can be used?

Back 23

a. Outbred
b. Inbred
c. Transgenic
d. All of the above

Hint 23

d.
All of the above

Front 24

Historic trend in Big Pharma favors which of the following species in preclinical studies?

Back 24

a. Dog
b. Rat
c. Mouse
d. rabbit

Hint 24

b.
Rat

Front 25

Which of the following is TRUE about advantage of using rat in preclinical studies?

Back 25

a. There is more classical physiology knowledge about rat versus mice
b. The production of transgenic rats is more efficient than mice
c. BAC (bacterial artificial chromosome) and YAC (Yeast artificial chromosome techniques far more developed in rats
d. Rat ES are easier to grow in vitro than mice

Hint 25

a.
There is more classical physiology knowledge about rat versus mice

Front 26

Which of the following is the regulatory agency for the drug approval in the USA?

Back 26

a. MHLA (Ministry of Health, Labor and Welfare)
b. CDC
c. FDA
d. CPMP (Committee for Proprietary Medicinal Products)

Hint 26

c. a=Japan, d= EU

Front 27

FDA requires immunotoxicity functional testing for all potential drugs.

Back 27

True or False

Hint 27

False. FDA requires this test if there is evidence of immunosuppression by standard methods (hematology, histology of immune related tissues). However, for CPMP of EU this test is mandatory for all INDs.

Front 28

What is IND?

Back 28

a. Investigational not available drug
b. Investigational new drug
c. Inexpensive new drug
d. Inactive new drug

Hint 28

b.

Front 29

Opossum esophagus is the closest model to human radiation-induced esophagitis.

Back 29

true or false

Hint 29

True

Front 30

Pig glucose sensing is closer to the human’s than other lab animals.

Back 30

True or False:

Hint 30

False, dog is true

Front 31

Primary PD refers to studies of the mode-of-action, whereas secondary PD refers to its potential toxicity.

Back 31

True or False:

Hint 31

True

Front 32

The therapeutic index is the ratio between effective dose to lethal dose in 50% of tested population (ED50 / LD50).

Back 32

True or False:

Hint 32

False. It is LD 50 / ED50

Front 33

The purpose of PD studies is to follow the fate of the candidate drug throughout of the body, especially the target organs.

Back 33

True or False:

Hint 33

False. It is PK

Front 34

The purpose of the PK studies is to establish the potency and efficacy the candidate drug by analyzing dose-response curve.

Back 34

True or False:

Hint 34

False. It is PD

Front 35

Safety pharmacology studies investigate potential undesirable PD effect on physiological function, regarding therapeutic range and above.

Back 35

True or False:

Hint 35

True

Front 36

Toxicokinetics refers to generation of PK data while conducting a toxicity study.

Back 36

True or False:

Hint 36

True

Front 37

Which of the following parameter(s) is (are) used in the assessment of the drug exposure

Back 37

a. AUC ( area under the curve of the plasma drug concentration-time curve)
b. Cmax (maximum peak plasma concentration)
c. Ctime (plasma concentration at given time)
d. All of the above

Hint 37

d. All of the above

Front 38

Which of the following is INCORRECT regarding single-dose toxicity studies?

Back 38

a. They are performed after phase I of human studies
b. Provide preliminary ideas about the target organ toxicity
c. Provide information about acute overdosing in humans
d. Provide information for calculating doses for repeat-dose studies

Hint 38

a. correct answer is 'Before'

Front 39

Which of the following is INCORRECT regarding acute studies?

Back 39

a. The drug is administrated in one or two doses
b. The period of the drug administration should not exceed 48 hrs
c. They are carried out in two species (rodent and nonrodent)
d. Test range should be from amounts that cause no adverse effect to a major toxicity
e. The drug is administrated in two routes (one intended for clinical use and another IV when feasible
f. Tested animals observed for 14 days

Hint 39

b. 24 hrs

Front 40

Which of the following is INCORRECT regarding repeated dose toxicity studies?

Back 40

a. The objective is to evaluate long-term effect of the drug in animal models
b. They are carried out in two species (rodent and nonrodent)
c. The duration of these studies range from 2 weeks to chronic, usually 6 months for rodents and 9 months for non-rodents
d. They are designed to support human clinical studies of Phase I and II only.

Hint 40

d.
They are designed to support human clinical studies of Phase I and II only. (phase III also)

Front 41

What are the first and second species of choice for local tolerance studies?

Back 41

a. Rat, Dog
b. Rabbit, Dog
c. Dog, Rat
d. Dog, Mouse
e. Rat, Mouse

Hint 41

b. Rabbit and Dog.
rodents are not considered relevant or adequate

Front 42

Currently, what is the preferred species for reproduction toxicity studies?

Back 42

a. Rabbit
b. Mouse
c. Dog
d. Rat

Hint 42

d. Rat

Front 43

The standard battery for genotoxicity test consists of:

Back 43

a. Two in vitro tests and one in vivo test
b. One in vitro test and one in vivo test
c. Two in vitro tests and two in vivo tests
d. One in vitro test and two in vivo tests

Hint 43

a. two in-vitro tests and one in-vivo test

Front 44

The in vitro examples for genotoxicity test are:

Back 44

a. Ames-Salmonella test
b. Mouse lymphoma TK test
c. a only
d. a and b

Hint 44

d. a and b

Front 45

Which of the following is UNTRUE regarding carcinogenicity studies?

Back 45

a. The neonatal mouse from outbred strains (eg., CD1) is considered medium term test model (1 year)
b. The Big Pharma recommends and prefers rat model
c. It usually requires 50 animals per gender and per group.
d. For transgenic mice, larger numbers of animals (100) are usually needed.

Hint 45

d. For transgenic mice, larger numbers of animals (100) are usually needed.

True answer is Fewer transgenic animals are needed, -> 25 per gender, per group

Front 46

Which of the following is INCORRECT regarding mouse local lymph node assay (LLNA)

Back 46

a. It is an alternative to the standard Buehler test in guinea pig
b. The test determines skin hypersensitivity to dermal and topical administration of agents
c. The substance injected in the mouse foot pad.
d. It provides quantitative results

Hint 46

c. It is for PLNA, LLNA is applied to the skin of the ear

Front 47

Popliteal Lymph node assay (PLNA) is used for autoimmunity studies.

Back 47

True or False

Hint 47

True

Front 48

Which of the following best describes “knockin” mouse line?

Back 48

a. Mouse having multiple copies of transgene at random loci
b. Mouse having a gene that can be disrupted temporarily
c. Mouse have a gene disrupted leading to absence of the gene product
d. mouse is generated by targeted insertion of the transgene at a selected loci

Hint 48

d.
mouse is generated by targeted insertion of the transgene at a selected loci

Front 49

Use of Small interfering RNA (siRNA) and short-hair pin RNA shRNA can be used to knock-down a gene instead of gene deletion by genetic engineering..

Back 49

True or False:

Hint 49

True

Front 50

A quantitative trait locus (QTL) is a region of DNA that is associated with a particular phenotypic trait - these QTLs are often found on different chromosomes. QTL mapping is the statistical study of the alleles that occur in a locus and the phenotypes (physical forms or traits) that they produce.

Back 50

True or False:

Hint 50

True