Hypolipidemics

Question 1

What is the mechanism of action of Niacin?

Answer 1

Reduction of liver triglyceride synthesis–leading to less hepatic VLDL production
Decreases lipolysis in adipose tissue–leading to lowered FFA transport to liver
Reduced hepatic clearance of APOAI–raising HDL

Question 2

What are the uses of Niacin?

Answer 2

Best agent to increase HDL
As good as vibrates and statins at lowering triglycerides
Lowers LDL
Hypertriglyceridemia and low HDL

Question 3

What are the side effects of Niacin?

Answer 3

Flushing
Pruritis of face and upper trunk
Rashes
Acanthosis nigricans–hyperpigmentation

Question 4

The use of Niacin is contraindicated in?

Answer 4

DM and gout pts

Question 5

Name the fabric acid derivatives (Fibrates)

Answer 5

Clofibrate
Gemfibrozil
Fenofibrate

Question 6

What is the mechanism of action of the fibrates?

Answer 6

Interacts with peroxisome proliferator activated receptor–PPARa to stimulate LPL synthesis –enhancing TG-rich lipoprotein clearance

Inhibits apoC III expression–enhancing VLDL clearance

Stimulation of apoAI and apoAII–increasing HDL

Question 7

What are the uses of the fibrates?

Answer 7

Reduction in VLDL–thus triglycerides
Little effect on LDL
small increase in HDL

Question 8

What are the side effects of the fibrates?

Answer 8

Potentiate oral anticoagulants
increase bile lithogenicity
Myositis flu-like syndrome

Question 9

Name the bile acid sequestrants

Answer 9

Colestipol
Cholestyramine
Colesevelam

Question 10

What is the mechanism of action of the bile acid sequestrants?

Answer 10

Very positively charged resins binds negative charged bile acids–inhibiting reabsorption and increasing cholesterol loss

Leads to increase in LDL receptors in liver–to make more cholesterol–decreasing LDL in blood

Question 11

What do the bile acid sequestrants do?

Answer 11

Decrease LDL

Slight increase in TG and HDL

Question 12

What are the side effects of the bile acid sequestrants?

Answer 12

Very safe –Only hypolipidemic indicated for children

Impaired fat soluble vitamin absorption

Question 13

When are the bile acid sequestrants contraindicated?

Answer 13

in hypertriglyceridemia

Question 14

What is the mechanism of action of the statins?

Answer 14

Inhibit HMG-CoA reductase formation of mevalonate

• -leads to activation of SREBP–a membrane-bound transcription factor that increases LDL-R synthesis and lessen degradation
• -reduction in cholesterol decreases VLDL synthesis–lowering TG

Question 15

What do the statins cause?

Answer 15

Reduce LDL and TG while increasing HDL

Used in the tx of dyslipidemia–reduces fatal and nonfatal CHD and strokes

Question 16

What are the newer statins with a longer half-life that allow them to be taken anytime of the day rather than at night like the older ones?

Answer 16

Atovastatin
Rosuvastatin
Pitavastatin

Question 17

Drug that inhibits enterocyte absorption of cholesterol in intestine?

Answer 17

Ezetimbe

Question 18

What is the mechanism of action of Ezetimbe?

Answer 18

Inhibits cholesterol absorption by enterocytes in jejunum leading to less cholesterol in chylomicrons–reduction in chylomicron remnant cholesterol delivery to liver

Question 19

What does ezetimbe cause?

Answer 19

Decreases LDL-C

Question 20

PCSK9 inhibitors that are 2nd line therapy for hypercholesterolemia not controlled by diet and statins?

Answer 20

Alirocumab and evolucumab

Question 21

What is the mechanism of action of Alirocumab and evolucumab?

Answer 21

Inhibits an endopeptidase–PCSK9 responsible for LDL-R degradation–results in higher numbers of LDL-Rs on hepatocytes