Dyslipidemia

What statins are more CYP3A4 dependent?

simvastatin, atorvastatin and lovastatin

What are examples of statins?

simvastatin, atorvastatin, rosuvastatin

What are other side effects of niacin?

vasodilation that could potentiate antihypertensive, diarrhea, and drug-induced hepatitis

In 2018 guidelines what is the focus on statins on?

"Its all about risk"

I.4. Which of the following is a major toxicity associated with gemfibrozil therapy? (A)Bloating and constipation (B) Cholelithiasis (C) Hyperuricemia (D) Liver damage (E) Severe cardiac arrhythmia

(B) Cholelithiasis

Case study I: A 35-year -old woman appears to have familial combined hyperlipidemia. Her serum concentrations of total cholesterol, LDL cholesterol, and triglyceride are elevated. Her serum concentration of HDL cholesterol is somewhat reduced. I.1. Which of the following drugs is most likely to increase this patient's triglyceride and VLDL cholesterol concentrations when used as monotherapy? (A) Atorvastatin (B) Cholestyramine (C) Ezetimibe (D) Gemfibrozil (E) Niacin

(B) Cholestyramine

II.4. Six months after beginning atorvastatin, the patient's total and LDL cholesterol concentrations remained above normal, and he continued to have anginal attacks despite good adherence to his antianginal medications . His physician decided to add ezetimibe. Which of the following is the most accurate description of ezetimibe's mechanism of an action? (A) Decreased lipid synthesis in adipose tissue (B) Decreased secretion of VLDL by the liver (C) Decreased gastrointestinal absorption of cholesterol (D) Increased endocytosis of HDL by the liver (E) Increased lipid hydrolysis by lipoprotein lipase

(C) Decreased gastrointestinal absorption of cholesterol

Case study I: A 35-year -old woman appears to have familial combined hyperlipidemia. Her serum concentrations of total cholesterol, LDL cholesterol, and triglyceride are elevated. Her serum concentration of HDL cholesterol is somewhat reduced. I.3. The patient is started on gemfibrozil. Which of the following is a major mechanism of gemfibrozil's action? (A) Increased excretion of bile acid salts (B) Increased expression of high-affinity LDL receptors (C) Increased secretion of VLDL by the liver (D) Increased triglyceride hydrolysis by lipoprotein lipase (E) Reduced uptake of dietary cholesterol

(D) Increased triglyceride hydrolysis by lipoprotein lipase

II.2. If the patient has a history of gout, which of the following drugs is most likely to exacerbate this condition? (A) Colestipol (B) Ezetimibe (C) Gemfibrozil (D) Niacin (E) Simvastatin

(D) Niacin

Case study II: A 43-year-old man has heterozygous familial hypercholesterolemia. His serum concentrations of total cholesterol and LDL are markedly elevated. His serum concentration of HDL cholesterol, VLDL cholesterol, and triglycerides are normal or slightly elevated. The patient's mother and older brother died of myocardial infarctions before the age of 50. This patient recently experienced mild chest pain when walking upstairs and has been diagnosed as having angina of effort. The patient is somewhat overweight. He drinks alcohol most evenings and smokes about 1 pack of cigarettes per week. II.1. Consumption of alcohol is associated with which of the following changes in serum lipid concentrations? (A) Decreased chylomicrons (B) Decreased HDL cholesterol (C) Decreased VLDL cholesterol (D) Increased LDL cholesterol (E) Increased triglyceride

(E) Increased triglyceride

Case study I: A 35-year -old woman appears to have familial combined hyperlipidemia. Her serum concentrations of total cholesterol, LDL cholesterol, and triglyceride are elevated. Her serum concentration of HDL cholesterol is somewhat reduced. I.2. If this patient is pregnant, which of the following drugs should be avoided because of a risk of harming the fetus? (A) Cholestyramine (B) Ezetimibe (C) Fenofibrate (D) Niacin (E) Pravastatin

(E) Pravastatin

What are other recommendations from the 2013 guidelines?

1. CK should not be routinely measured 2. Measured baselines ALT and only remeasure if symptoms suggest hepatotoxicity 3. Screen for diabetes 4. No recommendations for add-on therapy 5. Recheck lipid panel 4-12 weeks after initiation to assess for adherence not be therapy 6. Consider hypertriglyceridemia treatment if TG is >500 mg/dl

What counts as clinical ASCVD, and what should their treatment be?

1. Stroke 2. TIA 3. coronary artery disease with stable angina 4. Acute coronary syndrome 5. Stents 6. Peripheral vascular disease 7. aortic aneurysm Treatment should be high-intensity statin

How much of cholesterol is made by the liver cells and how much is consumed from diet?

20% from diet, 80% from liver cells

What are cholesterol absorption inhibitors?

A new class of antilipemic drugs also known as ezetimibe or zetia

When should LFT be monitored?

At the start of the treatment and every 6-12 weeks

What are the doses for moderate-intensity statin therapy? (2013)

Atorvastatin 10-20 mg Rosuvastatin 5-10 mg Simvastatin 40 mg Pravastatin 40 mg Lovastatin 40 mg

What are the doses for high-intensity statin therapy? (2013)

Atorvastatin 40-80 mg Rosuvastatin 20-40 mg

II.3. After being counseled about lifestyle and dietary changes, the patient was started on atorvastatin . During his treatment with atorvastatin, it is important to routinely monitor serum concentrations of which of the following? (A) Blood urea nitrogen (B) Alanine and aspartate aminotransferase (C) Platelets (D) Red blood cells (E) Uric acid

B) Alanine and aspartate aminotransferase

Why should fibric acid derivatives not be used with statins?

Because it increases myopathy

What should the treatment be for age 40-75 y?

Clinician-patient risk discussion: 1. Estimate 2. Personalize 3. Reclassify with management: 1. Life-style modifcation only 2. mod-int statin or 3. High-int statin

What is high-intensity statin therapy? (2013)

Daily dose that lowers LDL-C by > 50%

Who is under the category for moderate intensity statins to lower LDL 30-50%?

Diabetics, 40-75 years old with LDL 70-189 mg/dL, those with a 10-year risk >7.5%

A 58-year-old man presented with striking hypertriglyceridemia, elevated VLDL cholesterol, and depressed HDL was treated with a drug . Six months after drug treatment was initiated, his triglyceride and VLDL cholesterol have dropped dramatically and his HDL cholesterol level has doubled. Which of the following drugs is most likely to be the one that this man received? (A) Colestipol (B) Ezetimibe (C) Gemfibrozil (D) Lovastatin (E) Niacin

E. Niacin

What are omega-3 fatty acids?

Fish oils that help with hypertriglyceride and lead to decreased triglyceride synthesis by the liver

What are side effects of resins?

Flatulence, bloating, constipation and increased triglycerides

What is the major side effect of niacins and what can it be treated with?

Flushing This can be decreased with ASA such as aspirin

What are examples of fibric acid derivatives?

Gemfibrozil and fenofibrate

What should LDL-C >190 receive?

High intensity statins, no ASCVD risk is needed. if LDL remains >100, then add ezetimibe, but if multiple risk factors of future ASCVD occur then add PCSK9-1

What are fibric acid derivatives used for?

High triglycerides

Who falls under the category of very high risk of future ASCVD events and what is their treatment?

History of mult. major ASCVD events or 1 major ASCVD event and mult. high risk conditions Treatment includes high statins and if LDL-C remains >70, then non-statin therapy should be added first with ezetimibe and then PCSK9-I

Who is under the category of primary prevention?

LDL-C >190 Diabetes 40-7 years old Ages 40-75 with LDL-C 70-190 Ages 0-19 y Ages 20-39 y

When should statins be discontinued?

If the LFT increase to more than 3 times normal

When are PCKS9 inhibitors usually given with statins?

In order to furhter lower the LDL levels in patients with familial hypercholesterolemia and whenever the max tolerated statin theapy is not enough to control LDL-C levels in "very high risk" ASCVD patients

What the side effect of resins?

Increased triglycerides

What is special about resins?

It binds to other medications, so it much be taken 2 hours before those meds because it decreases their absorption and bioavailability

What is the benefit of resins?

It decreases the return of cholesterol to the liver, thus causing an uptake of LDL by the liver

What is the mechanism of action of cholesterol absorption inhibitors?

It inhibits cholesterol absorption from small intestine, thus emptying the hepatic free cholesterol pool

What is niacin?

It is a vitamin B that is given 100-300 times the dose to decrease LDL and TG and increase HDL

What should the treatment be for diabetes 40-75 years old ?

Moderate intensity statin, no need for 10 year ASCVD risk If they are at highest risk, or mult risk factors, high-intensity statin should be considered

What are contraindications to cholesterol absorption inhibitors?

Moderate to severe hepatic insufficiency

If a pt 40-75 without DM and LDL?70, and 10-year ASCVD risk of >7.5%, what should be the treatment?

Moderate-intensity statin if discussion of treatment options favors statin therapy

What is the very first recommendation before initiated statin therapy?

Pts should adopt a heart-healthy lifestyle: Eat less, eat smart, move more daily, don't smoke and don't gain weight

What happens if 0-19 y has diagnosis of familial hypercholesterolemia?

Statin

What is important to know about muscle symptoms in the 2013 guidelines?

Statins should be temporarily stopped, and be assessed for rhabdo; a lower dose of a different statin can be prescribed to see if a particular statin causes the muscle pain aka can be rechallenged with lower os same dose of statin

What causes dyslipidemia?

The hepatic cholesterol is full and satisfied with cholesterol, so then LDL remains in the endothelial cells, causing a build up

What are bile acid sequestrants? (resins)

They are chelating agents that bind bile acids int he intestines, forming an insoluble complex excreted in the feces

What is special about statins?

They are the best med to protect against IHD, decreases hepatic cholesterol resistance and best lipid drug that lowers mortality

What is the MOA of fibric acid derivatives?

They stimulated lipoprotein lipase, promoting the breakdown of VLDL and TG

Who is under the category for high intensity statins to lower LDL >50%? (2013)

Those with ASCVD and LDL >190

When should statins be given?

Those with a short half-life should be given at night since cholesterol synthesis is a nocturnal event

What is the MOA of niacin?

Unknown; Decreased VLDL synthesis and increase LPLase activity

When are cholesterol absorption inhibitors normally taken?

Usually given with statins to further lower the LDL levels using lower doses of statins

What are contraindications for statins?

active liver disease, pregnancy and lactation

What is the MOA of PCKS9 inhibitors?

as it inihibits the PCKS9 genes, more LDL receptors are recycled and present on the surface of liver cells to remove LDL from the blood

What are examples of resins?

cholestyramine and colesevelam

Who falls under the category of secondary prevention?

clinical ASCVD Very high risk of future ASCVD events Age >75 y

What is the goal for moderate-intensity statin therapy? (2013)

daily dose lowers LDL-C by 30% to <50%

What are PCSK9 inhibitors?

drugs that inhibit the PCSK9 enzyme in hypercholesterolemia patients

What are the most common side effects from statins?

elevated liver enzympes, myositis, myalgia and rhabdomyolysis

How often are PCSK9 inhibitors given?

every 2 weeks or once monthly as SC injection

What are side effects of fibric acid derivatives?

gall stones, LFT abnormalities, acute pancreatitis

If a pt 40-75 without DM and LDL>70, and 10-year ASCVD risk of 7.5%-19.9%, what should be the treatment?

if they have risk enhancing factors that favor initiation of statin therapy, but also consider measuring coronary artery calcium

What is the mechanism of statins?

inhibits HMG-CoA reductase to empty hepatic cholesterol free pool and reuptake LDL in the liver, decreasing LDL in the plasma

What are the side effects of PCSK9 inhibitors?

injection site reaction, "flu" like symptoms, increased blood sugar levels, nausea, fatigue and diarrhea.

What change does the 2013 ACC/AHA blood cholesterol guide focus on?

patients will no longer be treated to LDL targets

Which statins are less CYP dependent?

pravastatin, rosuvastatin