Antihyperlipidemia

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Bile Acid Resins fun facts

sequestered to the resin in the gut and excreted with the feces

Niacin (B3) MOA

strongly inhibits lipolysis of adipose tissue to decrease liver TG synthesis that is required for VLDL production

Fibrates MOA

works to activate peroxisome proliferator-activated receptors (PPAR-a) to decrease TAG concentration by increasing expression of lipoprotein lipase

PJ is a 5-year-old boy. At his checkup, the pediatrician notices cutaneous xanthomas and orders a lipid panel. Repeated measures confirm that the patient's serum cholesterol levels are high (936 mg/dL). Further testing confirms a diagnosis of homozygous familial hypercholesterolemia. Which of the following interventions will be least effective in this patient? (A) Atorvastatin (B) Ezetimibe (C) Lomitapide (D) Mipomersen (E) Niacin

(A) Atorvastatin

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 hav- ing angina of effort. The patient is somewhat overweight. He drinks alcohol most evenings and smokes about 1 pack of cigarettes per week. 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

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

A 35-year-old woman appears to have familial combined hyperlipidemia. Her serum concentrations of total cho- lesterol, LDL cholesterol, and triglyceride are elevated. Her serum concentration of HDL cholesterol is somewhat reduced. 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

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 hav- ing angina of effort. The patient is somewhat overweight. He drinks alcohol most evenings and smokes about 1 pack of cigarettes per week. 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 adher- ence 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

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

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 hav- ing angina of effort. The patient is somewhat overweight. He drinks alcohol most evenings and smokes about 1 pack of cigarettes per week. 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

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 hav- ing angina of effort. The patient is somewhat overweight. He drinks alcohol most evenings and smokes about 1 pack of cigarettes per week. 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

A 46-year-old woman with a history of hyperlipidemia was treated with a drug. The chart below shows the results of the patient's fasting lipid panel before treatment and 6 mo after initiating drug therapy. Normal values are also shown. Which of the following drugs is most likely to be the one that this patient received? (A) Colestipol (B) Ezetimibe (C) Gemfibrozil (D) Lovastatin (E) Niacin

(E) Niacin

A 35-year-old woman appears to have familial combined hyperlipidemia. Her serum concentrations of total cho- lesterol, LDL cholesterol, and triglyceride are elevated. Her serum concentration of HDL cholesterol is somewhat reduced. 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

HMG-CoA inhibitors (statins) MOA

Competitively inhibits HMG-CoA reductase to inhibit cholesterol synthesis

Niacin (B3) action

Decreased VLDL decreased LDL increases HDL (more than other medicines-benefit)

What is cholesterol absorption inhibitor?

Ezetimibe

Combinations worth consideration

Fibrate + Niacin used for increase TG and/or decreased HDL Fibrate + Bile resin used for increase LDL and TG

Excellent combinations

Statin + bile resin= synergy to decrease LDL Niacin + bile resin = decrease LDL, TG; increase HDL

What is HMG-CoA reductase?

atorvastatin

Cholesterol Absorption Inhibitor fun facts

can be combined with statins in one single tablet

Omega-3 fatty acids fun facts

can be found in aquatic foods or taken as a supplement EPA and DHA are components of polyunsaturated fatty acids

Fibrates fun facts

cannot administer in combination with statins or warfarin

What is a bile acid resin?

cholestyramine

Fibrates actions

decrease TG decrease LDL increase HDL

HMG-CoA inhibitors (statins) actions

decrease intracellular cholesterol increase number of LDL receptors on surface to promote uptake of LDL from blood decrease TAGs increases HDL Increases LDL catabolism

Cholesterol Absorption Inhibitor actions

decrease total cholesterol decrease LDL decrease TG

Bile Acid Resins MOA

exchange anions for bile acids in the small intestine to form an insoluble complex that can't be absorbed.

Niacin (B3) adverse effects

gastrointestinal irritation flushing hepatic toxicity hyperuricemia may reduce glucose tolerance

Fibrates contraindications

hepatic and renal dysfunction gallbladder disease pregnancy

Bile Acid Resins contraindications

high TG

HMG-CoA inhibitors (statins) fun facts

if liver enzymes 3x more than normal, discontinue the medicine

Omega-3 fatty acids actions

inhibit VLDL and TG synthesis increases HDL

HMG-CoA inhibitors (statins) contraindications

liver disease pregnancy category X

Bile Acid Resins action

loss of bile acids forces liver to use cholesterol endogenously to form new bile acids decrease LDL decrease TC increase TG

HMG-CoA inhibitors (statins) uses

lower cholesterol levels reduce risk of cardiovascular accidents slows progression of CAD

Gemfibrozil (fibrate) adverse effect

myopathy hepatic dysfunction cholestasis

HMG-CoA inhibitors (statins) adverse effects

myopathy hepatic dysfunction teratogen high doses=rhabdomyolysis

combine with caution

niacin + statin statin + fibrates

Niacin (B3) fun facts

niacin inhibits tubular secretion of uric acid so it can lead to gout


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