Lipid Lowering drugs part 3 Flashcards
What is the mechanism of plaque formation
LDL enters the artery wall, and is subject to different modifications—> oxidations
modified
LDL stimulates expression of MCP-1 in endothelial cells
MCP-1 in endothelial cells and tries to bring monocytes to attack LDL-c.
Monocytes turn into macrophages—-> more aggressive engulf modified LDL particles and then send signals (cytokines-TNF, and interleukins) to get more macrophages.
Increase synthesis of adhesion molecules and they attract more monocytes, while macrophages continue eating LDL-c and then they turn into foam cells—> these cells form the lipid core (fatty streak).
After fatty cap is formed and also promote inflammation. Metalloproteinases will break up cap and it can rupture—> form thrombosis.
VLDL and chylomicrons can to some extent do the same thing—get into blood vessels and create lesions
Where and how is HDL produced
it is made in the liver and intestine; in the liver it make HDL with apoproteins AI and AII
Explain HDL metabolism and reverse cholesterol transport
- HDL is made in liver or intestine as nascent particles with phospholipids and apolipoprotein A-1
- macrophage takes cholesteryl ester stores and hydrolysis them to free cholesterol
- the nascent HDL interacts w/ macrophages and other peripheral cells with the help of ATP-binding
- HDL picks up this free cholesterol and is further converted to mature HDL by cholesterol esterfying enzyme lecithin: cholesterol acyltransferase (LCAT)- which stabilizes cholesterol
- the free cholesterol is removed by selective up take by liver (takes only lipid ie. cholesterol) by using scavenger receptor class B type I receptors (SR-BI)
- this cholesterol is reused for bile acid synthesis
What are statins used to treat
dyslipidemia or primary cardio disease prevention
What is the effect of statins on LDL-c levels
the reduction is dose depenedent; LDL-c is reduced by 6% for each doubling of the dose
How are triglycerides reduced by statins
if the statins are 250mg/dL or more, the percent reduction is similar to LDL-c
(35-45% w/ 80mg of simvastatin and atorvastatin)
if its less than 250mg/dL reduction will not be greater than 25%
How are statins able to increase HDL-c
if a patient has normal HDL ranges
40-50mg/dL for men
50-60mg/dL for women
an increase of 5-10% can be expected
How does combining statins with bile acid sequestrants lowering drugs impact the body
statins + bile acid-binding resin: 20-30% greater reduction in LDL-c than just statins
mostly from chloestyramine and colestipol
How does cominging statins with niacin impact the body
it enhances the effect of statins but increases the risk for myopathy, when statin dose is 25% of maximum dose
How does combining statins and fibrate impact the body
its useful with patients that have hypertriglyceridemia and high ldl-c levels, combination will increase the risk of myopathy
use fibrate max dose + no more than 25% of each statins max dose
What is the triple therapy and how much does it reduce LDL-c
resin + niacin + statin; reduces LDL-c by 70%
What are the stages of muscle damage with statins
myalgia—> myopathy (muscle pain) 10x’s upper limit stop statin—> rhabdomyolysis (can cause death)
How does rhabdomyolysis cause death
causes kidney damage by increasing creatine kinase so high it can be removed and damages kidneys
What are the lipophilic statins
LETS ALL have SOME FOOD during LUNCH
Lipophilic statins:
Atorvastatin (3A4)
Simvastatin
Fluvastatin (2C9)
Lovastatin (3A4)
need more biotransformation to get to water soluble form
What are the water soluble statins
Wendy Romanced Peter Pan
Water soluble statins
Rosuvastatin (10% CYP 2C9 and 2C19)
Pravastain
Pitavastatin
