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PDSA > Block 8 > Flashcards

Block 8 Flashcards

1
Q

what is a SNP?

A

a common (1% or more) substitution of 1 nucleotide in a DNA sequence; the most common type of mutation that causes PGx responses

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2
Q

Which penicillin is the “anti-pseudomonal” penicillin?

A

Piperacillin (carbenicillin and ticarcillin aren’t available in the US anymore)

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3
Q

A repeat of a gene sequence or, in some cases, the whole gene

A

duplication

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4
Q

A mutation that results in the insertion of a different amino acid in the peptide chain

A

missense

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5
Q

What is the result of salt formation with inorganic bases (KOH) with penicillin?

A

Enhances water solubility (used for IV injections)

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6
Q

Identify whether the following would decrease efficacy or increase toxicity.

Increased activity of efflux transporters

A

Decrease efficacy

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7
Q

the organization that publishes guidelines that enable a translation of genetic laboratory results into actionable prescribing decisions for specific drugs.

A

CPIC

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8
Q

Interindividual variation in drug response is due to a difference in genetic makeup of the individual who is taking the drug

A

Pharmacogenomic response

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9
Q

What are the clinical uses of Penicillin G?

A

LAST MAN

L - Leptospira

A - Actinomyces

S - Streptococcus/Staphylococcus (not MRSA)

T - Treponema

MAN - Meningitis

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10
Q

Identify whether the following would decrease efficacy or increase toxicity.

Increased activity of drug targets

A

Increase toxicity

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11
Q

Which penicillins have broad-spectrum activity? How was that achieved?

A

Hydrophilic groups in the side chain increase G- activity, so NH2, OH, and COOH can be placed on the alpha-carbon next to the carbonyl to provide the greatest G- activity

PCAT

P - Piperacillin

C - Carbenicillin

A - Amoxicillin & Ampicillin

T - Ticarcillin

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12
Q

Identify whether the following would decrease efficacy or increase toxicity.

Reduced activity of enzymes that activate prodrugs

A

Decreased efficacy

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13
Q

rs stands for ________. The numbers are generated by ________ along with ________.

A

Reference Sequence

the numbers are generated by NCBI (national center for biotechnology information) along with NHGRI (National human genome research institute)

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14
Q

A genetic change that is “common”, defined as being observed in 1% of the population or more

A

Polymorphism

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15
Q

A unique identification number given to a reported mutation

A

rs number

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16
Q

Which drugs are broad-spectrum penicillins? What generations are they?

A

2nd - Ampicillin, Amoxicillin

3rd - Carbenicililn, Ticarcillin

4th - Piperacillin

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17
Q

Which penicillins are orally active and how were they made that way?

A

The R group of the aryl side chain is modified with an electron withdrawing group

VODKA

V - Penicillin V

O - Oxacillin

D - Dicloxacillin

K - Cloxacillin

A - Amoxicillin/Ampicillin

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18
Q

How can penicillins be made beta-lactamase resistant? Which ones ARE resistant?

A
  • insertion of a bulky group to the aryl side chain provides steric hindrance, preventing the drug from fitting into the active site

CONDEMN

C - Cloxacillin

O - Oxacillin

N - Nafcillin

D - Dicloxacillin

M - Methicillin

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19
Q

Identify whether the following would decrease efficacy or increase toxicity.

Decreased activity of influx transporters.

A

Decrease efficacy

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20
Q

a state of heterozygosity at 2 or more different mutation sites

A

Complex Heterozygote

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21
Q

Compare and contrast ampicillin and amoxicillin. What is their spectrum of activity?

A

Amp - oral or IV; oral availability is 40-50%; used in shigella infections, has a higher risk of causing diarrhea

Amox - only oral; 80% orally available; not used in shigella infections

HELPS Slaughter Enterococcus
H. influenza, E. coli, Listeria, P mirabilis, Salmonella, Shigella, Enterococcus

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22
Q

a ______ influence means that the genetic variant is the single cause of the variation in response.

A

causative

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23
Q

Salt formation at the C2 carboxyl of penicillins (with organic bases) results in what?

A

Insoluble drugs with long durations of action (used for IM injections)

24
Q

An association whose mission is to catalyze and lead research in precision medicine for the discovery and translation of genomic variation influencing therapeutic and adverse drug effects

A

PGRN

25
Q

What variation leads to different penicillin analogs?

A

Variation of the acyl side chain

26
Q

Identify whether the following would decrease efficacy or increase toxicity.

Increased activity of influx transporters

A

Increase toxicity

27
Q

a mutation that results in the insertion of a stop codon in the peptide chain

A

nonsense

28
Q

The study of genetic influences on interindividual variation in drug response

A

Pharmacogenomics

29
Q

What are the limitations of penicillin G?

A
  • orally inactive
  • short duration of action due to rapid renal excretion
  • narrow spectrum of activity (G+ only)
  • sensitive to beta-lactamase
30
Q

The study of the entire set of gene transcripts in an organism

A

Transcriptomics

31
Q

a small insertion or deletion of a single or a few nucleotides (usually -5)

A

indel

32
Q

Nomenclature for variants of CYP450 genes was established by

A

Human Cytochrome P450 Allele Nomenclature Committee

33
Q

The general term for a permanent change in a DNA sequence in a population

A

mutation

34
Q

Identify whether the following would decrease efficacy or increase toxicity.

Reduced activity of enzymes that metabolize or clear drugs.

A

increase toxicity

35
Q

Which drugs are included in beta-lactam antibiotics?

A

Penicillins

Cephalosporins

Carbapenems

Monobactams

Clavams

36
Q

The percentage of people with a mutation who express the associated outcome

A

penetrance

37
Q

A kind of study that examines millions of mutation sites across an entire genome looking for differences in cases and controls

A

GWAS

38
Q

Define the MOA of beta-lactam antibiotics.

A

The penicillins and cephalosporins fit into the active site of transpeptidase because they mimic the enzyme’s substrate (D-ala-D-ala)

39
Q

Identify whether the following would decrease efficacy or increase toxicity.

Reduced activity of drug targets.

A

Decrease efficacy

40
Q

What is the most common cause of resistance to beta-lactam antibiotics?

A

Beta-Lactamase enzyme (cleaves the ring and inactivates it)

41
Q

a type of duplication or deletion mutation in which the variation is a difference in the normal number of times a DNA sequence is repeated and this difference is associated with diseases, disorders, or PGx responses

A

CNV (copy number variation)

42
Q

the study of the entire set of DNA in an organism

A

Genomics

43
Q

The cross linking in bacterial cell walls is catalyzed by which enzyme?

A

bacterial transpeptidase aka penicillin binding protein (PBP)

(it is a serine protease)

44
Q

A pharmacogenomics knowledge base that encompasses clinical information including dosing guidelines and drug labels, potentially clinically actionable gene-drug associations, and genotype-phenotype relationships.

A

PharmGKB

45
Q

a mutation that does not change the amino acid sequence in the peptide chain

A

synonymous

46
Q

a ______ influence means there is another cause for the variable response, but the mutation adds to the response.

A

modifying

altering factors such as severity, time to onset, and duration of the response are examples

47
Q

a mutation that changes the amino acid sequence in a peptide chain, either by insertion of a different amino acid or insertion of a stop codon

A

non-synonymous

48
Q

Define the mechanism of MRSA resistance.

A

The presence of the “mec” gene is responsible for resistance

  • the mec gene encodes for an altered PBP (to PBP2a). PBP2a has lower affinity for beta-lactamase antibiotics
49
Q

list some beta-lactamase inhibitors.

A

CAST

C - clavulanic acid

A - Avibactam

S - Salbactam

T - Tazobactam

50
Q

An uncommon (<1%) substitution of 1 nucleotide in a DNA sequence

A

SNV (single nucleotide variation)

51
Q

Which penicillins are anti-staphylococcal?

A

COND

C - Cloxacillin

O - Oxacillin

N - Nafcillin

D - Dicloxacillin

52
Q

Identify whether the following would decrease efficacy or increase toxicity.

Decreased activity of efflux transporters.

A

Increase toxicity

53
Q

Gene names are established by the

A

HGNC - HUGO Gene Nomenclature Committee

HUGE = Human Genome Orgnization

54
Q

What is the purpose of beta-lactamase inhibitors and when are they used?

A
  • have no antibacterial activity themselves, but they possess a beta-lactam ring

when used in combination with antibiotics, beta-lactamase will target the inhibitors instead so that broad-spectrum beta-lactams will be able to overcome plasmid mediated beta-lactamase resistance

55
Q

PGx responses are categorized as affecting _____ or _____

A

efficacy or toxicity

PDSA (6 decks)

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