Lecture 13: Drugs to Treat Hyperlipidemia

Question 1

What are the 6 drug classes used to treat Hyperlipidemia? (S/E/P/B/F/N)

Answer 1

Statins, Ezetimibe, PCSK9-I, Bile Acid Sequestrants, Fibrates, Niacin

Question 2

Statins

What is its lipid lowering MOA and what are 4 Non-Lipid Lowering MOAs? (PS/RI/RED/DT)

Answer 2

MOA: competitively block active site of HMG-CoA reductase (no mevalonic acid production)

NL MOA: plaque stabilization, red. inflammation, reverse endothelial dysfunction, dec. thrombogenicity

Question 3

What are 3 contraindications of statin use? (HD/EAL/P)

What damage can statins cause to the body?

Answer 3

1. active hepatic disease
2. persistent elevations in aminotransferase lvls
3. pregnancy and breastfeeding

• statins can cause rhabdomyolysis without inc. creatine kinase (bilateral and symmetric)

Question 4

What are 3 adverse effects of statin use? (DM/LI/AKI)

Answer 4

1. inc. risk of developing diabetes
2. possible severe liver injury (rare)
   
   • ALT > AST (distinguish from liver from muscle)
3. AKI (rhabdomyolysis –> myoglobinuria)
   
   • more likely at higher doses
   • only in pts. with rhabdomyolysis

Question 5

What enzyme metabolizes statins and what drug should be reduced if taken with statins?

What pt. population are at inc. risk of myopathy from statins?

Answer 5

• uses CYP450 enzymes
• statins affect vitamin K antagonists, so pts. taking WARFARIN should reduce that dose
• older East Asian pts are at inc. risk of myopathy

Question 6

Ezetimibe

What is its MOA, what 2 drugs can it be used in combo with, and what are its 3 contraindications (AHD/SHI/P)

Answer 6

MOA: cholesterol absorption inhibitor at the brush border of intestines and liver (dec. LDL-C; 2nd most common after statin)
- inhibits NPC1L1 protein (sterol transporter)

Combo: with statins and fenofibrate

CI: active hepatic disease, moderate-severe hepatic impairment, pregnancy/breastfeeding (if being used with statin)

Question 7

Which drug, Ezetimibe or PCSK9-I, should be the second drug added to a statin regime?

Answer 7

EZETIMIBE

Question 8

PCSK9-Inhibitors

What are the 2 drugs of this family (A/E), what is its MOA, and what pts. is it indicated in?

Answer 8

Drugs: Alirocumab and Evolocumab

MOA: blocks serine protease that cleaves LDL receptors at serine residues, causing inc. in # of available LDL receptors

I: pts with Familial Hypercholesterolemia and atherosclerotic cardiovascular disease

Question 9

Bile Acid Sequestrants

What is their MOA, what is it contraindicated in, what is its adverse effect, and what pt. population should use caution with use?

Answer 9

MOA: reduce LDL-C lvls by binding to bile acids, causing fecal excretion and inc. hepatic synthesis of bile acids from cholesterol (inc. LDL use)

CI: pts. wit dysbetaproteinemia

AE: dec. absorption of fat soluble vitamins

• caution in pts. with phenylketonuria

Question 10

What are the 3 Bile Acid Sequestrant drugs? (C/C/C)

Answer 10

colesevelam, colestipol, cholestyramine

Question 11

Fibrates

What is their MOA, what enzyme does Fenofibrate effect and what does it lead to, and what should Gemfibrozil not be taken with and why?

Answer 11

MOA: activate PPARalpha which inc. liver enzymes that inc. triglyceride metabolism, inducing LPL activity and production of HDL

• Fenofibrate inhibits OCT2 activity which can inc. serum creatinine levels
• Gemfibrozil should not be taken with statins due to inc. muscle toxicity (Fenofibrates do not inc. risk)

Question 12

What are the 3 Fibrate drugs? (F/FA/G)

What is gemfibrozil used for?

Answer 12

fenofibrate, fenofibric acid, gemfibrozil

• gemfibrozil used for primary prevention of CAD

Question 13

What can fibrates lead to the formation of?

Who are fibrates contraindicated in (2)?

Answer 13

GALLSTONES –> leading to cholelithiasis

CI: pts with significant liver disease and breastfeeding/nursing pts

Question 14

What two drugs should fenofibric acid NOT be given with?

What enzyme does Gemfibrozil inhibit?

Answer 14

• should not be given with niacin and statins due to lack of cardiovascular benefit when treating high cholesterol
• Gemfibrozil inhibits CYP2C8

Question 15

What are the 2 Niacin drugs and how are they taken?

What are the 3 MOAs of Niacin?

What are 4 adverse effects of use? (DM/UA/LE/MT)

Answer 15

Niacor (oral tablet) and Niaspan (oral extended release tablet)

MOA: inhibit FFA from adipose tissue, inc. LPL activity (inc. chylomicron removal), and dec. VLDL/LDL synthesis

AE: inc. blood sugar (diabetes), inc. uric acid lvls, inc. liver enzyme lvls, muscle toxicity

Question 16

What drug is Niacin given with to promote regression of atherosclerotic disease with?

Answer 16

bile acid binding resin