Dyslipidemia drugs… the powerpoint

Question 1

WHich 2 statins are prodrugs? Where are they activated?

Answer 1

LOVASTATIN
SIMVASTATIN

Metabolized in GI tract to active form.

CYP3A4 metabolizes them.

Question 2

How does STATIN use up regulate LDL receptors in the liver?

Answer 2

Cleavage of Transcription regulator SREBP, which occurs when intracellular cholesterol levels in the liver get too low.

Question 3

What is the most effective statin? (Causes the greatest decrease in LDL cholesterol?)

Answer 3

HIGH INTESNITY Atorvastatin followed by Rosuvastatin.

Atorvastatin causes a 40-80% reduction in cholesterol levels

Rosuvastatin causes a 20-40% decrease

Remember: these are dose dependent. Lower doses (moderate intensity therapy) with these same drugs won’t lower the LDL levels as much.

Question 4

Atorvastatin is commonly called….

Answer 4

Lipitor

Question 5

Which statin is dependent on CYP3A4 for metabolism?

Answer 5

LOVASTATIN
SIMVASTATIN
These 2 need it to be activated,

Atorvastatin needs CYP34 as well, to be eliminated. NOT activated.

Question 6

All statins undergo what metabolic reaction for elimination?

Answer 6

GLOCARONIDATION via UGT1A1

Question 7

If you drink grapefruit juice, will that have an effect on your Statin regimen?

Answer 7

YES! Statins are predominately eliminated by CYPS, and inhibiting them will increase their half-life in the body.

Question 8

What statin is metabolized by a means other than CYPS?

Answer 8

Pravastatin is metabolized via Sulfation

Question 9

Side effects of HMG-COA Reductase inhibitors?

Answer 9

Mild GI distress

Increased liver enzymes indicating hepatic dysfx (ALT/AST)

Sleep disturbance (?)

Question 10

Can a pregnant woman take statins?

Answer 10

NO! Statins are in Pregnancy Category X.

Question 11

What’s another contraindication of HMG-CoA Reductase inhibitors?

Answer 11

Liver Disease

Question 12

Can you take bile acid sequestrates (the “coles” drugs) with liver disease?

Answer 12

YES!

Question 13

MOA of Bile Acid Sequestrants

Answer 13

(+) charged resins that bind (-) charged bile acids as they are secreted into the gut, preventing their recycling/reabsorption.

With no more bile acids, the liver converts its cholesterol stores into the synthesis of new bile acids, reducing the amount of stored cholesterol.

This causes increase in LDL receptor synthesis as well, because stores are depleted. More LDL is taken in from the periphery.

Question 14

What Bile Acid Sequestrant can you take as either a pill or a tablet?

Answer 14

Colestipol

Question 15

Toxicity associated with Bile Acid Sequestrants.

Answer 15

Minor. Very well tolerated drug, and one of the safest dyslipidemia drugs on the market.

GI irritation, fat soluble vitamin deficiency

Question 16

You take an oral B-blocker at the same time as colesevelam. Is there an interaction? How do you fix this problem?

Answer 16

YES! Colesevelam (the bile acid sequestrate) prevents the absorption of the B-blocker.

Always take other drugs 1 hour before, or 2-4 hours after the bile acid sequestrate.

Question 17

What is the common nomenclature prefix for all bile acid sequestrates?

Answer 17

“coles”

Think gallbladder…. bile acid…. choles…

Question 18

MOA of Ezetamibe?

Answer 18

Prevents absorption of dietary cholesterol.

Commonly used in conduction with a STATIN

(Different, complimentary MOAs)

Question 19

How is Ezetamibe better than Bile Acid Resins?

Answer 19

It does not cause a fat soluble vitamin deficiency. (AEDK)

It also prevents not only dietary cholesterol absorption, but prevents bile acid cholesterols from getting absorbed as well.

Question 20

What 3 drugs/dietary supplements primarily function to lower Triglycerides and raise HDL cholesterol?

Answer 20

Fibrates

Niacin

Fish Oil (Omega 3-Polyunsaturated fatty acids)

Question 21

To lower LDL specifically, which drugs would you use?

Answer 21

Statins
Bile acid sequestrates
Ezetamibe

Question 22

Is Ezetamibe a prodrug or in active form when taken?

Answer 22

Prodrug metabolized to its active form in liver.

Question 23

Name the 2 Fibric Acid Derivatives

Answer 23

Gemfibrozil

fenofibrate

Question 24

MOA of Fibric Acid Derivatives

Answer 24

Ligand for the Ligand-activated PPARa Receptor, which regulated the transcription of lipid metabolizing substrates.

In adipocytes: up regulation of LPL

In liver: Increase fatty acid oxidation, limiting Acetyl CoA, reducing cholesterol synthesis

Increases HDL by promoting synthesis of ApoA1 (The HDL apoprotein)

Overall: Increase HDL, Decrease VLDL

Question 25

Toxicity of Fibrates

Answer 25

Nausea of most common, increased liver enzymes, gallstones

Question 26

If your patient has renal failure, which fibrate do you give them?

Answer 26

Gemfibrozil

Question 27

MOA of niacin: (many of them)

Answer 27

Raise HDL levels by decreasing its catabolic rate

Reduces VLDL synthesis in liver, which also reduces LDL

Lowers Triglycerides via Increase in LPL

Question 28

When can you use niacin?

Answer 28

Pretty much every disease.

Question 29

How do you prevent the flushing toxicity of Niacin?

What are the other toxicities?

Answer 29

The main toxicity of flushing of the skin for a few days when starting a regimen. Use aspirin or NSAIDs to tone it down.

Others:
Hyperuricemia
Glucose Intolerance

Question 30

If you want to reduce the risk of atherosclerotic heart disease or IHD, or CHD in your patient, which dyslipidemia drug would you choose?

Answer 30

a STATIN

The only one in this class that has preventative action against heart disease and atherosclerosis.

Question 31

If you take Fish Oil, what aspect of your lipid profile will lower?

Answer 31

Triglycerides. Nothing else.

Question 32

WHat is a major toxicity of Gemfibrozil?

Answer 32

Gallstones –> due to increased bile secretion of cholesterol

Decreased hematocrit

Nausea

Skin rashes