dyslipidemia treatment

Question 1

List statin benefit groups and statin intensities recommended

Answer 1

1. Clinical ASCVD – high intensity. 2. LDL-C >190 mg/dL without secondary cause – high intensity. 3. Primary prevention – moderate or high intensity (Diabetes, age 40-75 years, LDL-C 70-189 mg/dL). 4. Primary prevention – moderate intensity (No diabetes, age 40-75 years, LDL-C 70-189 mg/dL + 7.5% risk of CVD event in the next 10 years.)

Question 2

statins MOA

Answer 2

Inhibit HMG CoA reductase. Decrease hepatic pool of free cholesterol. Increase expression of LDL receptors on cell membranes. Increase catabolism of VLDL and LDL. Decrease LDL-C concentrations

Question 3

What is the 6% rule?

Answer 3

With each statin dose doubling, LDL-C falls by 6%

Question 4

statins side effects

Answer 4

abnormal AST and ALT, myopathy, cognitive impairment, new onset T2D

Question 5

Determinant of statin myopathyq

Answer 5

SLCO1B1*5

Question 6

List bile acid sequestrants

Answer 6

cholestyramine, colestipol and colesevelam- aka resins. Clinical evidence

Question 7

Bile acid sequestrants MOA

Answer 7

Inhibit reabsorption of bile acids stimulating conversion of cholesterol to bile acids. Reduced cholesterol content in hepatic cells then stimulates LDL receptor synthesis and LDL uptake by liver

Question 8

Bile acid sequestrants side effects

Answer 8

bloating, nausea, anal irritation, inhibits RX absorption

Question 9

List agents that inhibit cholesterol absorption

Answer 9

plant stanol esters and sterol esters - no clinical evidence

Question 10

Function of Ezetimibe

Answer 10

selective cholesterol absorption inhibitor- blocks cholesterol absorption at intestinal brush border. Binds to Niemann-Pick C1-like 1 and inhibits it from incorporating into clathrin coated vesicle, blocking absorption

Question 11

management of very high LDL

Answer 11

Maximally tolerated statin + ezetimibe + resin + fenofibrate + niacin. If > 200 mg/dL on maximum therapy one of two newly approved drugs(mipomersen or lomitapide) and/or LDL apheresis.

Question 12

Mipomersen MOA

Answer 12

targets Apo B at point of synthesis and secretion

Question 13

Lomitapide MOA

Answer 13

inhibits MTP in liver and intestine

Question 14

Fibrates MOA

Answer 14

PPAR alpha agonist - reduces triglycerides by increasing fatty acid oxidation in muscle and liver (main)

Question 15

fibrates adverse reactions and contraindications

Answer 15

Fenofibrate: skin rash, myopathy, increased LFTs, increased creatinine. Gemfibrozil: cholelithiasis, myopathy, GI upset. Contraindicated in severe renal or hepatic dz

Question 16

fish oils- clinical evidence

Answer 16

Three secondary prevention studies have shown modest benefit in decreased CVD. No studies at present have demonstrated decreased CVD events in patients with hypertriglyceridemia

Question 17

components of fish oils

Answer 17

EPA and DHA omega-3 fatty acids

Question 18

Fish oils MOA

Answer 18

decrease hepatic triglyceride production and VLDL-TG secretion

Question 19

nicotinic acid clinical evidence

Answer 19

unknown

Question 20

Nicotinic acid MOA

Answer 20

Decreases lipolysis in adipose tissue (transiently). In liver, increases AMP kinase, FFA oxidation, decreases TG synthesis and decreases VLDL synthesis

Question 21

nicotinic acid contraindications and side effects

Answer 21

skin rash, liver disease, hyperuricemia or gout, active peptic ulcer of IBD, impaired glucose tolerance