PG

Question 1

Her2+ gene treatment?

Answer 1

Trastuzumab or herceptin

Question 2

treatment of oncogene V600E BRaf melanoma?

Answer 2

vemurafenib

Question 3

treatment of myelogenous leukaemia

Answer 3

gleevec or imatinab

Question 4

is haemophilia a simple disease and what does it affect?

Answer 4

simple genetic disease only affecting on gene - Factor 8 decrease in co-ag cascade

Question 5

whats the gene that causes late onset alzhiemers called?

Answer 5

apolipoprotein E

Question 6

how many variants of apolipoprotein?

Answer 6

E2,E3,E4

Question 7

How much of a risk do you have to develop alzhiemers if you have one parent with E4 variant

Answer 7

4x

Question 8

how much of a risk do you have of developing late onset alzheimers if you have both parents with the E4 variant

Answer 8

10x

Question 9

difference between the variant (alleles) E4 and E2 apolipoprotein genes

Answer 9

E2 decreases risk of Azmrs

E4 increases risk of Azmrs

Question 10

How are the variants caused?

Answer 10

SINGLE NUCLEOTIDE POLYMORPHISM

Question 11

which genes that code for cytochrome p450 enzymes help treatment with warfarin? (anticoagulant)

Answer 11

CYP2C9

VKORC1 (vitamin k reductase)

Question 12

which cytochrome p40 enzyme gene codes for anti-platelet drugs? and what are antiplatelet drugs called?

Answer 12

CYP2C19

and clopidogrels

Question 13

what is the main component of coagulation?

Answer 13

fibrin

fluid converted into gel/like fibrin mixture

Question 14

fibrous network/wall is responsible for what?

Answer 14

• trapping and stopping microorganisms from entering the body
• stopping bleeding by forming platelet plug
• forming a bases for initiation of repair

Question 15

What are co-agulation factors

Answer 15

plasma proteins that are inactive in the liver but become active once they are faced with vessel injury which causes them to undergo proteolytic cleavage - become active

Question 16

phospholipids

Answer 16

found on the membrane of the platelets which are ACTIVATED

Question 17

calcium ions

Answer 17

help coagulation factors to be activated

Question 18

what does thrombin (factor 2 produce)

Answer 18

fibrinogen is activated (soluble) which is converted to fibrin (insoluble)

Question 19

describe extrinsic pathway of coagulation

Answer 19

Factor 3 is converted into factor 3a
then factor 7 is converted into 7a which activates factor 10a from factor 10
then thrombin is activated (2a)
thrombin causes fibrinogen to be converted into fibrin
factor 13 causes the formation of fibrin polymer

Question 20

describe the intrinsic pathway of coagulation

Answer 20

factor 12 into 12 a then 11 into 11a then causes 9 into 9 a which causes 8 into 8a
8a and 9a activate 10a from 10
causes thrombin to be activated (factor 2 to 2a)
causes thrombin to cause fibrinogen to convert into fibrin
factor 13 a causes fibrin polymer to be formed

Question 21

intrinsic pathway caused by:

Answer 21

exposure to endothelial collegen

Question 22

extrinsic pathway caused by

Answer 22

exposure to tissue factor (released during injury)

extrinsic occurs first

Question 23

what is deep vein thrombosis?

venous thrombosis

Answer 23

thrombus formed in deep veins such as legs due to sluggish flow - this causes clots to form
this causes the venous thromboembolism to bud off into pulmonary ciruculation and block pulonary artery

Question 24

treatment for deep vein thrombosis

Answer 24

anticoagulants such as warfarin

Question 25

what is arterial thrombosis? | diseases associated?

Answer 25

platelets start to aggregate and form clots in the arteries which may cause myocardial infarction and ischaemic stroke

Question 26

treatment of arterial thrombosis

Answer 26

anticoagulants long term/prophylaxis | fribrinolytics - clot busters (short term)

Question 27

which four diseases does warfarin treat

Answer 27

``` DVT pulmonary embolisms arterial fibrillation heart valve receivers and can be used as aprophylactic drug (days before opperation) ```

Question 28

whats a narrow therapeutic range

Answer 28

small changes in the dose can cause major changes so have to administer dose carefully

Question 29

side effects of warfarin

Answer 29

haemorrhage and bleeding

Question 30

what does vitamin K? reductase do?

Answer 30

VKR is cofactor for GGCX (gamma glutamyl carboxylase) | which activates factor 2,7,9 and 10 by binding calcium

Question 31

what does warfarin do to vitamin k reductase

Answer 31

acts as an antagonist - inhibits it inhibiting doesnt allow it to co-factor for GGCX which prevents activation of factor 2,7,9 and 10 by calcium binding not happening DECREASES COAGULATION

Question 32

dosing depends on what?

Answer 32

genetics, weight, other medications and diseases and diet

Question 33

which enzymes cause variability in pharmacokinetics of warfarin?

Answer 33

CYP2C9(liver enzyme) and VKORC1 (site of warfarin action - antagonist)

Question 34

what are the two stereoisomers of warfarin?

Answer 34

R and S at chiral centre 9 | S is 5x more effective at breaking down cytocrhome p450 in the liver to produce metabolites

Question 35

what metabolites of CYP2C9 are formed?

Answer 35

6 and 7 hydroxy metabolites

Question 36

which variant of CYP2C9 is more effective?

Answer 36

variant 3

Question 37

what causes the variant CYP2C9 2

Answer 37

arginine replaced with cystine at 144 position

Question 38

what causes variant cyp2c9 3

Answer 38

isoleucine replaced with leucine at 359 position

Question 39

``` warfarin dose in lower in patients with what phenotype? a. TT b.CC c.CT why? ```

Answer 39

a.TT because people with this genotype have a rare recessive bleeding disorder (deficiency of vitamin K reductase) affected in INTRON 1

Question 40

Highest sensitivity to dosage?

Answer 40

variant 3 (more effective breakdown)

Question 41

highest resistance to warfarin?

Answer 41

VKORC1 - coding region cause warfarin resistance

Question 42

which ethnicity has more CYP2C9 3 and 2?

Answer 42

caucasians more than asians and africans

Question 43

which ethnicty has more noncoding (C) VKORC1?

Answer 43

asians

Question 44

which ethnicity has more coding TVKROC1?

Answer 44

cacasians more than africans

Question 45

whats the function first approach or genomic first approach?

Answer 45

genes should be analysed first before drug administration to find the best match of drug to suit the variations in each individual

Question 46

why percision medicine now?

Answer 46

we have the human genome project we have better technologies (biomed analysis) now we have better datasets to record information in

Question 47

ethical and legal issues with percision medicine

Answer 47

confidentiality of genetic info fairness (insurance, employers) - psychological impact - reproductive use (having kids) - clinical issues (doctors need to know how to handle patient - quality control) - uncertanities with complex diseases (just cause you have succeptibility doesnt mean you have disease) -expensive