Dyslipidemia drugs… the powerpoint Flashcards
WHich 2 statins are prodrugs? Where are they activated?
LOVASTATIN
SIMVASTATIN
Metabolized in GI tract to active form.
CYP3A4 metabolizes them.
How does STATIN use up regulate LDL receptors in the liver?
Cleavage of Transcription regulator SREBP, which occurs when intracellular cholesterol levels in the liver get too low.
What is the most effective statin? (Causes the greatest decrease in LDL cholesterol?)
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.
Atorvastatin is commonly called….
Lipitor
Which statin is dependent on CYP3A4 for metabolism?
LOVASTATIN
SIMVASTATIN
These 2 need it to be activated,
Atorvastatin needs CYP34 as well, to be eliminated. NOT activated.
All statins undergo what metabolic reaction for elimination?
GLOCARONIDATION via UGT1A1
If you drink grapefruit juice, will that have an effect on your Statin regimen?
YES! Statins are predominately eliminated by CYPS, and inhibiting them will increase their half-life in the body.
What statin is metabolized by a means other than CYPS?
Pravastatin is metabolized via Sulfation
Side effects of HMG-COA Reductase inhibitors?
Mild GI distress
Increased liver enzymes indicating hepatic dysfx (ALT/AST)
Sleep disturbance (?)
Can a pregnant woman take statins?
NO! Statins are in Pregnancy Category X.
What’s another contraindication of HMG-CoA Reductase inhibitors?
Liver Disease
Can you take bile acid sequestrates (the “coles” drugs) with liver disease?
YES!
MOA of Bile Acid Sequestrants
(+) 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.
What Bile Acid Sequestrant can you take as either a pill or a tablet?
Colestipol
Toxicity associated with Bile Acid Sequestrants.
Minor. Very well tolerated drug, and one of the safest dyslipidemia drugs on the market.
GI irritation, fat soluble vitamin deficiency
You take an oral B-blocker at the same time as colesevelam. Is there an interaction? How do you fix this problem?
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.
What is the common nomenclature prefix for all bile acid sequestrates?
“coles”
Think gallbladder…. bile acid…. choles…
MOA of Ezetamibe?
Prevents absorption of dietary cholesterol.
Commonly used in conduction with a STATIN
(Different, complimentary MOAs)
How is Ezetamibe better than Bile Acid Resins?
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.
What 3 drugs/dietary supplements primarily function to lower Triglycerides and raise HDL cholesterol?
Fibrates
Niacin
Fish Oil (Omega 3-Polyunsaturated fatty acids)
To lower LDL specifically, which drugs would you use?
Statins
Bile acid sequestrates
Ezetamibe
Is Ezetamibe a prodrug or in active form when taken?
Prodrug metabolized to its active form in liver.
Name the 2 Fibric Acid Derivatives
Gemfibrozil
fenofibrate
MOA of Fibric Acid Derivatives
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
Toxicity of Fibrates
Nausea of most common, increased liver enzymes, gallstones
If your patient has renal failure, which fibrate do you give them?
Gemfibrozil
MOA of niacin: (many of them)
Raise HDL levels by decreasing its catabolic rate
Reduces VLDL synthesis in liver, which also reduces LDL
Lowers Triglycerides via Increase in LPL
When can you use niacin?
Pretty much every disease.
How do you prevent the flushing toxicity of Niacin?
What are the other toxicities?
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
If you want to reduce the risk of atherosclerotic heart disease or IHD, or CHD in your patient, which dyslipidemia drug would you choose?
a STATIN
The only one in this class that has preventative action against heart disease and atherosclerosis.
If you take Fish Oil, what aspect of your lipid profile will lower?
Triglycerides. Nothing else.
WHat is a major toxicity of Gemfibrozil?
Gallstones –> due to increased bile secretion of cholesterol
Decreased hematocrit
Nausea
Skin rashes
