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

Pharmacogenetics and pharmacokinetics Flashcards

(46 cards)

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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?

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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?

21
Q

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

22
Q

What is 6-mercaptopurine used to treat?

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A

-Cytotoxic chemotherapy for leukaemia

23
Q

What does the antimetabolite of 6-mercaptopurine inhibit?

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A

-Inhibits synthesis of purine nucleotides

24
Q

What is the major ADR that occurs when patients take

6-mercaptopurine?

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A

Myelosuppression

25
What is Myelosuppression?
A condition in which bone marrow activity is decreased
26
Does 6-mercaptopurine have a wide or narrow therapeutic window?
Narrow
27
What is 6-mercaptopurine metabolised by?
TPMT -Thiopurine S-methyl transferase
28
Myelosuppression inhibits precursor cells that differentiate into myeloidal cells into replication, less myeloidal cells produced. TRUE OR FALSE?
TRUE
29
If both alleles are functional will patient have high or low TPMT? (Trimodal distribution)
High
30
If patient has one allele functioning, will the patient have high/low or intermediate TPMT activity?
Intermediate
31
If both alleles of patient are dysfunctional will have high/low TPMT activity?
Low
32
What is warfarin metabolized by?
-Metabolized by CYP 2C9
33
What are the two variants that substantially reduce CYP anzyme activity?
- Arg144cys | - Ile358Leu
34
Warfarin inhibits the synthesis of what enzyme and what is the name of this enzyme?
- vitamine K | - Vitamine K epoxide reductase
35
Different alleles encode variants of enzyme with different sensitivities to warfarin. TRUE OR FALSE?
TRUE
36
What are cisplatin, carboplatin, and oxaliplatin used for?
Platinum based compounds used as chemotherapy for cancer which platinate DNA and prevent replication
37
How do these compounds work (cisplatin, carboplatin, and oxaliplatin)?
- 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
How are platinum containing compounds cleared?
-They are cleared after conjugation of tripeptide called glutathione
39
Many of the enzymes used in the clearance of platinum compounds have several polymorphisms. TRUE OR FALSE?
-TRUE
40
What are statins used for?
To reduce cholesterol levels
41
What is the major ADR that can occur when taking statins?
-Myopathy
42
Statins inhibit the synthesis of cholesterol in the liver. TRUE OR FALSE?
TRUE
43
What is the site of action of statins?
Hepatocytes
44
How does OATP1B1 work to cause myopathy?
- 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
What is does OATP1B1 do?
-It is a transporter that is involved in moving the statin from the blood and taking it up to the liver
46
How is the 521 C causing myopathy?
By preventing the drug being pumped to the liver

Alan's lecture - Pharmacology (16 decks)

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