Antihyperlipidemia
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