Pharmacogenomics

Question 1

Why does ACE inhibitors work less effectively on the African American population?

Answer 1

Africans have more volume dependent hypertension and lower renin too, hence diuretics work better than other hypertensives.

Question 2

Why does the Framingham 10 year risk score have no ethnicity option?

Answer 2

The initial study was done in a predominantly homogenous Caucasian population

Question 3

Where do mutations/polymorphisms occur?

Answer 3

In the protein coding genes

Question 4

What is the 80’s theory on DNA?

Answer 4

99.9% of DNA is junk

Question 5

What is the 2000’s theory on DNA?

Answer 5

All DNA is important, most DNA mutations are found in the 99.9% junk DNA

Question 6

What are mutations known as?

Answer 6

SNPS

Question 7

What are the details of SNPS?

Answer 7

• single nucleotide polymorphism
• happens every 250 bp
• 55 million are known
• might be in the gene/coding or non coding
• they are drug response markers

Question 8

How do SNPS cause mutation?

Answer 8

They can code for protein mutations or interact with the cell

Question 9

How are SNPS good drug response markers?

Answer 9

Certain SNPS respond to drugs better than others. Checking what type of SNPS you have can help to determine the best therapy using Spartan RX.

Question 10

What drug is the most difficult dose to adjust?

Answer 10

Warfarin because it is variable depending on the food you eat and other medications you take. Warfarin needs to be processed by the liver, so other things that go through liver will affect it. Since it is so variable, dosing needs to be checked regularly.

Question 11

What kinds of foods interact with Warfarin?

Answer 11

Avocado, high Vitamin K (warfarin is Vit K antagonist) , Acetaminophen

Question 12

What was Warfarin’s previous use?

Answer 12

Rat Poison

Question 13

What does Warfarin do?

Answer 13

It is anti-thrombotic by preventing coagulation (blood clots).

Question 14

What are the features of Warfarin?

Answer 14

• very cheap and safe
• easy to reverse
• eating habit dependent
• MANY trips to coagulation/thrombin clinic to get checked for proper dosing
• costs a lot to switch to another medication

Question 15

What is Sepsis

Answer 15

An infection of the blood that causes coagulation. It can be causes by practically any infection.

Question 16

Why does skin appear black in patients with Sepsis?

Answer 16

The extremities appear black because blood becomes jelly like and there is no blood flow due to increased coagulation.

Question 17

What is the prognosis for Sepsis?

Answer 17

• A third of sepsis patients die
• half of septic shock patients die (body goes into shock even if the bacteria has been removed)
• Major cause of death in the ICU
• ICU management vital signs due to lack of knowledge

Question 18

How do you manage Sepsis?

Answer 18

• antibiotics
• intubation
• Vasopressor (they are given epinephrine/vasopressin to increase heart rate bc they are in a hypotensive state)
• anti-coagulants (help to make the blood that is jelly go away)

Question 19

What are the conclusions from the Sepsis trial?

Answer 19

Certain SNIPS are associated with mortality in Sepsis

Question 20

What was the previously approved drug for Sepsis and why is it no longer in use?

Answer 20

Xigris. It did not have enough beneficial evidence and it costs 8,000 per treatment.

Question 21

How does Xigris work?

Answer 21

It is an activated protein C which blocks key coagulation pathways (the pathways that cause blackening of extremities). Since Sepsis increases coagulation (conversion of fibrinogen (water soluble) to fibrin (not soluble, more like a glue) than the platelets form blood clots. Sepsis also blocks Plasminogen (plasminogen is responsible for getting rid of the glue (fibrin) thicker liquid)
Xigris inhibits this, and turns the thick liquid to thinner blood.

Question 22

What is another method for treating sepsis?

Answer 22

Statins can be used for sepsis to decrease the amount of inflammatory cytokines.