Chapter 6

Question 1

pharmacogenomics is the branch of science

Answer 1

Concerned with the identification of genetic attributes of an individual to lead to variable responses to drugs.

Question 2

Pharmacogenomics seeks to identify

Answer 2

Patterns of genetic variation that are subsequently employed to guide the design of optimal medication regimen for individual patients

Question 3

This Human Genome Project

Answer 3

The groundbreaking effort to map the entire human genome. While 95% of the sequence of all human DNA was established, resulting in identification of open reading frames for many human proteins

Question 4

Single nucleotide polymorphisms

Answer 4

Genetic differences that account for allotypic phenotype variations

Question 5

How many SNP’s have been identified

Answer 5

1.4 million

Question 6

What is the importance of the 2011 study by LII, Zhang, Zhou, Stoneking, and Tang on the heterogeneity in drug metabolizing genes in globally defined populations

Answer 6

Explains the origin of genetic polymorphism and drug metabolism enzymes and purports to provide an evolutionary rationale for such differences across ethnicities

Question 7

Another word for an individual’s genetic makeup

Answer 7

Genotype

Question 8

Genotypes result from

Answer 8

Genetic recombination or mixing of genes from that individual’s parents. All of the DNA contained in an individual cell is known as the genome of the individual, a word formed by combination of gene and chromosome. It represents all of the genes that individual can express. Interestingly, even though two unrelated people share about 99.9% of the same DNA sequences, less than 0.1% difference between them translate into difference in 3 million nucleotides.

Question 9

The 0.1% difference in DNA sequence between two unrelated people create variance that are known as

Answer 9

Snips or SNP’s

Question 10

Haplotypes

Answer 10

Her large portions of genetic material that tend to travel together. Understanding how S&P’s and haplotypes make humans genetically unique to the current focus of much genetic research. The completion of the Human Genome Project, as well as the mapping of snips and haplotypes, has allowed for the field of pharmacogenetics to understand the variability of drug metabolism seen across individuals and populations

Question 11

Genetic polymorphism

Answer 11

Multiple differences of DNA sequence found in at least 1% of the population

Question 12

Genomics

Answer 12

The study of complete set of genetic information present in the cell, an organism, or species

Question 13

Pharmacogenetics

Answer 13

The study of influence of hereditary factors on response of individual organisms to drugs

Question 14

Pharmacogenomics

Answer 14

The study of the effects of genetic differences among people and the impact that these differences have on the uptake, effectiveness, toxicity, and metabolism of drugs

Question 15

SNP

Answer 15

Single nucleotide polymorphism

Question 16

Standard adopted nomenclature is used in identifying specific genes. Provide an example

Answer 16

CYP2D6 written in italics refers to the normal copy of the gene, whereas CYP2D6*1 (prnounced star 1) refers to the first identified natural variant or mutant copy of this gene

Question 17

The Greek philosopher and mathematician Pythagoras

Answer 17

Recorded the first individual difference of drug administration and 510 BCE when he noted that some patients developed hemolytic anemia after ingesting the fava bean.

Question 18

The term pharmacogenetics was first coined by

Answer 18

Vogel in 1959, and until 1962 was it defined as the study of hereditary and in response to drugs by callow. Since 1962 the term has been used to refer to the effects of genetic differences on a person’s response to drugs.

Question 19

Attribution of peripheral neuropathy slow acetylation of isoniazid in some patients treated for tuberculosis due to genetic diversity and enzyme

Answer 19

N-acetyltransferase

Question 20

The rate of acetylation of a drug such as isoniazid is clinically relevant because it determines the rate of

Answer 20

Elimination of the drug from body. Thus the visuals known as slow acetylators will metabolize the drum slowly, allowing greater residence time in the body and enhanced toxicity.

Question 21

the ultimate promise of pharmacogenomics is the

Answer 21

Possibility that knowledge of the patient’s DNA sequence might be used enhance drug therapy to maximize efficacy, target drugs only to those patients were likely to respond, avoid ADRs. Increasing number of patients respond to therapeutic regimen with a con commitment decrease in the incidence of ADRs is the promise of this information.

Question 22

Genetic differences in metabolism were first realized by the observation that sometimes

Answer 22

Very low or very high concentrations of drug were found in some patients despite their heaven been given the same amount of the drug.

Question 23

Genetic polymorphism occurs when

Answer 23

Difference in the allele responsible for the variation is a common occurrence.

Question 24

An allele is an alternative form of a gene. The gene is called polymorphic when

Answer 24

Allelic variations occur throughout a given population and a stable rate of less than 1%. Under such circumstances, genes will exist somewhat frequently alongside wild type chains. The mutant genes one code for production of immune proteins in these populations. Immune proteins will, in turn, interact with drugs in different manners, sometimes wide, sometimes significant.

Question 25

Mono genic traits by themselves cannot explain

Answer 25

The complexity of drug metabolism. Genes interact on a complex level yielding different responses with honey upon which genes a wild type which show mutant phenotypes.

Question 26

Poor metabolizes

Answer 26

Lack a working enzyme

Question 27

Intermediate metabolizes

Answer 27

Are heterogeneous for one working, one wild type allele and one mutant allele

Question 28

Extensive metabolizes

Answer 28

Have to normally functioning alleles;

Question 29

Ultra-rapid metabolizes

Answer 29

Have more than one copy of functioning enzymes

Question 30

Drug metabolism generally involves the conversion of lipophilic substances and

Answer 30

Metabolites into more easily excludable water-soluble forms.

Question 31

Drug metabolism takes place mostly in the

Answer 31

Liver and is divided into two major categories

Question 32

Phase 1 metabolism

Answer 32

Oxidation reduction in hydrolysis reactions

Question 33

Phase 2

Answer 33

Conjugation reactions

Question 34

Poor to intermediate metabolizes clinical implications

Answer 34

Prodrug will be metabolized slowly into the active drug metabolite. May have accumulation prodrug. After drug will be metabolized slowly into inactive metabolite. Potential for accumulation of active drug. Patient requires lower dosage of medication.

Question 35

Ultra-rapid metabolizes clinical implications

Answer 35

Prodrug rapidly metabolized into active drug. No dosage adjustment needed. Active drug rapidly metabolized into inactive metabolites leading to potential therapeutic failure. Patient requires hot dose of active drug.

Question 36

Phase 1 metabolism enzymes are responsible for approximately

Answer 36

59% of the ADRs cited in the literature.

Question 37

CYP’s are generally located in

Answer 37

In the plasmid reticulum and mitochondrial human cells, of which the ER isoforms are of particular importance to the field of drug metabolism. In terms of their organ distribution, they are found in greater amounts in the liver and in the intestine and to somewhat lesser extent in other organs, such as the skin, brain, lungs, and kidneys.

Question 38

Hepatic, renal, and intestinal ER CYP’s are involved in

Answer 38

The biotransformation of a plethora of drugs and Indo genus substances in humans mainly by oxygenation of the target substrate molecule and mediated by differential oxidation states of the central iron atom and the enzyme. Due to this oxygenation reaction, CYP’s are classified as monooxygenases.

Question 39

High genetic variability of the cytochrome P4 50 (CYP 450)

Answer 39

Constitutes the most important of the phase 1 metabolizing enzymes, the total of 57 genes encoding for CYP 450 enzymes.

Question 40

CYP2d6

Answer 40

Up to 90% of drugs are metabolized via cyp2D6. Phenotypic variations in some enzymes can have an astounding outcome on drug therapy. For example, 1000 fold difference has been observed in the rate of metabolism of some substrates due to differences in CYP2d6 isoenzymes

Question 41

CYP 2D six is a well studied instance of a DME coding gene that exhibits polymorphism. This gene product acts on many Zeno biotics, including many common prescription drugs such as

Answer 41

Selective serotonin reuptake inhibitors, tricyclic antidepressants, beta blockers, calcium channel blockers, and others.

Question 42

21% of this population has the altar metabolize or phenotype

Answer 42

Asian

Question 43

35% of the population carries

Answer 43

Nonfunctional 2D six allele. This nonfunctional allele may increase the risk of ADRs especially in patients with polypharmacy.

Question 44

CYP2C9 Medications and drug effect linked ot polymorphism

Answer 44

tolbutamide, warfarn, phenytoin, nsaids

Anticoagulant effect on warfarin

Question 45

CYP2D6 medications and side effects

Answer 45

Beta-blockers, antidepressants, antipsychotics, coding, and many more

Tardive dyskinesia from antipsychotics, narcotic side effects, efficacy, independence,

Question 46

Dihydropyrimidine dehydrogenase medicaitons an effects

Answer 46

fluorouricil

flurouracil neurtoxicity

Question 47

thiopurine methyltranferase medications and effects

Answer 47

mercaptopurine, thioguanine, azathioprine

thiopurine t toxicity and efficacy; risk of second cancers

Question 48

Angiotensin-converting enzyme’s medications and effects

Answer 48

Lisinopril

Renal protective effects, cardiac indices, blood pressure, immunoglobulin a, nephropathy