3. Peters - Hyperlipidemia Flashcards
Signs and Symptoms of Hyperlipidemia
- Typically asymptomatic until a CV events occurs
- Pancreatitis: directly related to high TGs, >500
- Chest pain: clot in chest, MI or angina
- Shortness of breath: clot moves into lungs
- Speech or movement impaired: clot in brain (stoke)
What is Dyslipidemia?
- A combination of elevated TC, elevated TGs, elevated LDL cholesterol, and low HDL
What are the risk equivalents for coronary heart disease?
Hint, there’s 5
- Diabetes
- PAD
- CAD - MI or angina
- Abdominal aortic aneurysm (triple A syndrome)
- Framingham risk >20%
What are some major CV risk factors?
Hint, there’s 5
- Cigarette smoking
- Hypertension, BP >140/90
- Low HDL
- Family history of premature CHD
- Age, men >45 and women >55
What are the target numbers based on ATP III?
TC: 40 mg/dL
TGs:
Non-Pharm Therapy for Hyperlipidemia
- Diet counseling
- Weight management
- Increased physical activity
- Smoking cessation
- Hypertension treatment
Peters - MOA of statins
- HMG-CoA Reductase inhibitor
- Decrease cholesterol synthesis, lowers intracellular cholesterol which stimulates up regulation of LDL receptors increasing the intake of LDL, and lowering circulating LDL levels
Pleiotropic effects of statins
Help decrease plaque and clot formation
What are the two high intensity statins and what are their available strengths?
- Atorvastatin, 40-80mg
2. Rosuvastatin, 20-40mg
What are the 3 main statin drug interactions to avoid?
- CCB (nondihydropyridines)
- Gemfibrozil
- Grapefruit juice
What are the main adverse effects of statins?
- Headache and GI intolerance
- Myalgia, which can lead to myopathy and/or rhabdomyolysis
- New onset diabetes
- Potential increase in LFTs
Managing statin therapy - how to determine if a pt is “intolerant”
Try 3 statins, 3 different times, at three different strengths.
If a pt does not respond, then they are considered statin intolerant
Peters - Fibrates and their MOA
Fenofibrate and Gemfibrozil
- Agonist of proliferator-activated receptor-alpha
- inhibit TG synthesis, increase LPL activity, increase breakdown of VLDL and increase HDL synthesis
What is the net effect of statins?
Decreased TC
Decreased LDL
What is the net effect of Fibrates?
Significantly decreased TGs –> main effect
Decreased TC
Decreased LDL
Increased HDL
What are the main adverse effects of Fibrates?
- GI complaints
- Changes in LFTs
- Hypoglycemic effects in pts on sulfonureas
- Renal dysfunction
MAIN: Gemfibrozil inhibits break down of statins
Examples of Bile Acid Sequestrants and their MOA
Cholestyramine, colestipol, colesevelam
MOA: Block the reabsorption of bile acids back into the liver, allows for easy excretion out through feces
What is the net effect of bile acid sequestrants?
Decreased TC
Decreased LDL
What are the main adverse effects of bile acid sequestrants?
- GI distress
- Potential increase in TG, should not be taken when pt >300 mg/dL
- Impaired fat soluble vitamin absorption
- Reduced bioavailability of other meds, separated dosing is needed
What is Niacin’s MOA?
Decreased hepatic production of VLDL and LDL
What is Niacin’s net effect?
BIG EFECTS:
- Decreased TGs, decreased LDL, and increased HDL
What are Niacin’s main adverse effects?
- Flushing, but tolerance will develop over time
- P.U.D
- Exacerbate gout
- Exacerbate diabetes
- Hepatotoxicity w/ ER formulation
How should we monitor niacin?
Base line labs including: liver function tests, A1C and uric acid levels
- Labs should be repeated every 6 months
What is Ezitimibe’s MOA?
Block cholesterol absorption by inhibiting NPC1L1 receptor at the brush boarder
What is Ezitimibe’s net effect?
Decreased TC
Decreased LDL
What is Ezitimibe’s main adverse effects?
Well tolerated, but can induce statin side effects when in combo.
What are the two main sources of omega-3 fatty acids?
DHA and EPA
What is omega-3 fatty acids MOA? What is different about DHA?
Both lower TGs, but DHA can increase LDL levels
What are the main side effects of omega-3 fatty acids?
GI disturbance, increased bleeding risk, and skin changes
What is lomitapide’s MOA?
Blocks to MTP receptor and inhibits the assembly of ApoB lipoproteins, leading to a decrease in LDL production
What is Lomitapide main adverse effects?
Chest pain, and hepatic distress (steatosis)
What is the MOA of Mipomersen? What what is its black box warning?
MOA: Oligonucleotide inhibitor of Apo-B synthesis, decreasing LDL synthesis
Black box warning: liver function, watching for elevated LFTs
What are mipomersen’s maid adverse effects?
Injection site rxn (subQ injections), flu-like reactions (fatigue, headache, fever)
What is Evolocumabs MOA?
PCSK-9 inhibitor, allows for more LDL receptors to be placed on the membrane of cells, increasing LDL intake and decreasing circulating LDL levels
What are the main changes to the ACC/AHA guidelines?
Hint, there’s 6
- 4 groups named that would benefit from statin therapy
- New perspective on LDL and non-HLD treatment goals
- Global risk assessment for primary prevention
- Updated safety recommendations
- Role of biomarkers and noninvasive tests
- Future updates to cholesterol guidelines
MUST KNOW THIS!
What are the 4 statin benefit groups?
- Individuals w/ clinical ASCVD >21yrs old
- Individuals w/ LDL >190 mg/dL and >21 yrs old
- Individuals 40-75 yrs old w/ diabetes and LDL between 70-189 mg/dL
- Individuals 40-75 yrs old w/ LDL 70-189 mg/dL and an estimated 10 year ASCVD risk >7.5% (basically everyone else who is high needs a statin)
What is the definition of ASCVD?
PASS to a statin
P: peripheral artery disease
A: acute coronary syndromes (MI, angina)
S: stent; coronary revascularization
S: stroke and TIA
In the new global risk assessment for primary prevention what are the two event predicted and the 8 risk factors assessed?
Events: nonfatal/fatal MI or nonfatal/fatal stroke
Risk factors: sex, age, TC, HDL, systolic BP (Tx, Y or N), smoking (Y or N), race (white/other or AA), diabetes (Y or N)
Epidemiology of Hyperlipidemia
- TCs and LDLs increase throughout life
- Almost half of Americans > 20 yrs have a TC >200mg/dL
- Half of those at boarder line for high risk are unaware they have hypercholesterolemia
