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Alan's lecture - Pharmacology > Pharmacogenetics and pharmacokinetics > Flashcards

Pharmacogenetics and pharmacokinetics Flashcards

1
Q

What is polymorphisms?

A

Genetic variation within a population

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2
Q

What SNPs stand for?

A

Single nucleotide polymorphisms

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3
Q

What occurs in synonymous SNP?

A

Both alleles of a gene encode the same polypeptide

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4
Q

What occurs in non synonymous SNP?

A

The alleles encode a different polypeptide

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5
Q

How can pharmacogenetics be described?

A

The study of how individual patient’s genome affects their response to a drug

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6
Q

How does inheritance affect the a patient’s response to a drug?

A

Inheritance can affect the efficacy and adverse events of patients

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7
Q

What are the differences between monogenic and polygenic?

A
  • Monogenic - a single gene affects the response

- Polygenic - multiple genes affect the response

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8
Q

What is suxamethonium used for?

A
  • Causes relaxation of muscles/ can be used to facilitate surgery
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9
Q

What is isoniazid used for?

A

-Treatment of TB

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10
Q

What is the major ADR that can occur when using Isoniazid?

A

-peripheral neuropathy

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11
Q

What enzyme metabolises Isoniazid?

A

N-acteyl transferase 2 (NAT2)

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12
Q

How does NAT2 work?

A

It transfers an acetyl group onto the isoniazid, which inactivates isoniazid

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13
Q

How many SNPs alleles are known for isoniazid?

A

27

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14
Q

What are fast and slow acetylators?

A
  • Fast acetylators : are patients that can efficiently metabolise isoniazid
  • Slow acetylators : Patients that metabolise isoniazid more slowly
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15
Q

Which catageroy of patients slow or fast acetylators are at greater risk of peripheral nerve damage?

A

Slow acetylators

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16
Q

What other drug is also metabolised by NAT2 and what is is used to treat?

A

Procainamide - used to treat arrythmias

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17
Q

What causes patients to have reduced 2D6 P450 ACTIVITY?

A

Allele encodes enzyme with comprimised catalytic activity, causing deletion of gene

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18
Q

What are patients at risk of when suxamethonium is degraded slowly?

A

Prolonged paralysis

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19
Q

What occurs when patients have reduced 2D6 function, and provide examples?

A
  • They have increased response to drugs that are metabollically inactivated by 2D6. e.g nortryptyline
  • They also get a decreased response to pro-drugs that are activated by 2D6. E.g codeine and tamoxifen
20
Q

2D6 genotype can influence survival of breast cancer patients receiving tamoxifen. TRUE OR FALSE?

A

TRUE

21
Q

Patients with increased 2D6 P450 activity do not have multiple copies of 2D6 and are ultrarapid metabolizers. TRUE OR FALSE?

A

FALSE

22
Q

What is 6-mercaptopurine used to treat?

A

-Cytotoxic chemotherapy for leukaemia

23
Q

What does the antimetabolite of 6-mercaptopurine inhibit?

A

-Inhibits synthesis of purine nucleotides

24
Q

What is the major ADR that occurs when patients take

6-mercaptopurine?

A

Myelosuppression

25
Q

What is Myelosuppression?

A

A condition in which bone marrow activity is decreased

26
Q

Does 6-mercaptopurine have a wide or narrow therapeutic window?

A

Narrow

27
Q

What is 6-mercaptopurine metabolised by?

A

TPMT -Thiopurine S-methyl transferase

28
Q

Myelosuppression inhibits precursor cells that differentiate into myeloidal cells into replication, less myeloidal cells produced. TRUE OR FALSE?

A

TRUE

29
Q

If both alleles are functional will patient have high or low TPMT? (Trimodal distribution)

A

High

30
Q

If patient has one allele functioning, will the patient have high/low or intermediate TPMT activity?

A

Intermediate

31
Q

If both alleles of patient are dysfunctional will have high/low TPMT activity?

A

Low

32
Q

What is warfarin metabolized by?

A

-Metabolized by CYP 2C9

33
Q

What are the two variants that substantially reduce CYP anzyme activity?

A
  • Arg144cys

- Ile358Leu

34
Q

Warfarin inhibits the synthesis of what enzyme and what is the name of this enzyme?

A
  • vitamine K

- Vitamine K epoxide reductase

35
Q

Different alleles encode variants of enzyme with different sensitivities to warfarin. TRUE OR FALSE?

A

TRUE

36
Q

What are cisplatin, carboplatin, and oxaliplatin used for?

A

Platinum based compounds used as chemotherapy for cancer which platinate DNA and prevent replication

37
Q

How do these compounds work (cisplatin, carboplatin, and oxaliplatin)?

A
  • Platinum can physically attach to DNA on cacer cells, when DNA becomes platinated; this prevent cells from replicating and as a consequence cells are no longer able to replicate DNA, leading to cell arrest as they go through the cell cycle.
38
Q

How are platinum containing compounds cleared?

A

-They are cleared after conjugation of tripeptide called glutathione

39
Q

Many of the enzymes used in the clearance of platinum compounds have several polymorphisms. TRUE OR FALSE?

A

-TRUE

40
Q

What are statins used for?

A

To reduce cholesterol levels

41
Q

What is the major ADR that can occur when taking statins?

A

-Myopathy

42
Q

Statins inhibit the synthesis of cholesterol in the liver. TRUE OR FALSE?

A

TRUE

43
Q

What is the site of action of statins?

A

Hepatocytes

44
Q

How does OATP1B1 work to cause myopathy?

A
  • The C at 521 impairs the uptake into hepatocytes
  • Obtain greater AUC
  • Therefore greater accumulation of drug in muscle tissue
  • Both alleles need to be affected for significant myopathy
45
Q

What is does OATP1B1 do?

A

-It is a transporter that is involved in moving the statin from the blood and taking it up to the liver

46
Q

How is the 521 C causing myopathy?

A

By preventing the drug being pumped to the liver

Alan's lecture - Pharmacology (16 decks)

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