Flashcards in Lipoprotein Metabolism: Part 2, Dyslipidemia Deck (43)
What is dyslipidemia?
A disorder of lipoprotein metabolism, including lipoprotein overproduction of deficiency
**increased level of "bad" LDL cholesterol and also a decrease in the "good" HDL
Major risk factor for cardiovascular disease and 1 in 5 deaths is due to it
What is coronary heart disease?
Disease of the blood vessels supplying the heart muscle
What is cerebrovascular disease?
Disease of the blood vessels supplying the brain
What is peripheral arterial disease?
Disease of blood vessels supplying the arms and legs
What is rheumatic heart disease?
Dmg to the heart muscle and heart valves from rheumatic fever, caused by streptococcal bacteria
What is congenital heart disease?
Malformations of heart structure existing at birth
What is deep vein thrombosis and pulmonary embolism?
Blood clots in the leg veins, which can dislodge and move to the heart and lungs
What are the non-modifiable risk factors for cardiovascular disease?
family history of cardiac problems
What are antihyperlipidemic agents?
Drugs or natural products that can be used to reduce cholesterol, triglycerides or both.
What are the antihyperlipidemics?
HMG CoA reductase inhibitors (statins)
Cholesterol absorption inhibitors
Fibric acid derivatives (fibrates)
Omega-3 fatty acids
Bile acid sequestrants
What is the mech of action of HMG CoA reducatse inhibitors (statins)?
Competive inhibitor of HMG CoA reductase, which catalyzes the rate-limiting step of cholesterol synthesis
**liver is the primary target
What is the number 1 choice to reduce LDL-c?
HMG CoA reductase inhibitor (statins)
What is lipophilicity and the side effects?
Lipophilic statins penetrate muscle cell at higher degree than hydrophilic statins
**this leads to a pronounced effect in disturbing the normal activity of muscle by inhibiting CoQ10
What are the adverse effects of statins?
Most common is myopathy
Myalgia and cramp are more common than estimated from clinical trials
Can cause liver toxicity due to statin accumulation
What is the mechanism of statin myopathy?
They inhibit HMG-CoA reductase which leads to less production of mevalonate pathway metabolites, including CoQ10
Why do you have to worry about taking grapefruit juice with a statin?
Some statins are metabolized in the intestine by an enzyme called CYP3A
Grapefruit juice contains compounds called furanocoumarins that inhibit CPY3A, this results in more drug being absorbed, making it more powerful and can result in severe myopathy and liver toxicity
Is rosuvastatin inhibited by grapefruit juice?
What happens if a person takes a statin and a triglyceride reducing drug like gemfibrozil?
They could be at a greater risk of statin side effects
How do you deal with the side effects of taking a statin?
1. Take a break from statin therapy (10-14 days off the med can help to determine whether aches and pains are due to statins instead of soemthing else
2. switch to another statin
3. take it easy when exercising
4. reduce the dose of statin or alternate daily dosing
5. add ezetimibe along with statin
6. add bile acid sequestrants
What is the first AHA/ACC cholesterol treatment guideline?
All pts (> 21 years of age) with any form of CVD or LVL-C>190 mg/dl
treat with high dose statins
atorvastatin 40-80 mg or rosuvastatin 20-40 mg with the aim to reduce LDL-C by >50%
What is the second AHA/ACC cholesterol treatment guideline?
all pts with diabetes (age 40-75 years) with LDL-C 70-189 mg/dl, even without evidence of CVD should receive statin therapy
Treatment: Moderate dose statins, Atorvastatin 10-20 mg, rosuvastatin 5-10 mg to reduce LDL by 30-50%
***HIGH dose of statin is recommended for the same group with high CVD risk
What is the third AHA/ACC cholesterol treatment guideline?
As previsouly, a specific target of LDL-C goal (<70 or <100) is not recommended
**Also the fourth is pts need to receive intensive lifestyle management
Why is the LDL-C goal os low for diabetics?
Its because they tend to produce more small LDL particles.
What is the example of cholesterol absorption inhibitors?
What is the mech of action for cholesterol absorption inhibitors?
Blocks absorption of cholesterol in the intestine and liver
This involves NPC1L1, which is the target of ezetimibe which results in lower LDL with little effect on HDL and triglycerides
**usually added with statin when LDL goal is not achieved
What is the most preferred drug combo with a statin?
Its ezetimibe if the LDL-C goal is not met after max dose statin
What is Vytorin?
its a combo of simvastatin and ezetimibe
Has been shown to reduce LDL-c over just taking the single statin drug
What is a PCSK9 inhibitor?
Its a secretory protease in the liver that binds to LDLR and leads to degradation and as a result more LDL particle will be cleared from the circulation
Target and inactivate PCSK9
**dont cause issue with CoQ10
What are the PCSK9 inhibitors?