Anti-lipid drugs

Question 1

HMG CoA reductase inhibitors have what functions?

Answer 1

• Block synthesis of cholesterol

- INCREASE uptake of LDL into hepatocytes via LDL-receptor

Question 2

What are some other HMG CoA reductase inhibitor functions?

Answer 2

1. Increase endothelial NO and vasorelaxation
2. Stabilize arterial plaques, and reduce risk of thrombosis
3. Reduce inflammation in atherogenesis
   * 4. Reduce Platelet activation and risk of VTE (43% reduction)*

Question 3

Some statins should only be taken at night, why is that so?

Answer 3

Because liver synthesis peaks between midnight and 2am

Question 4

Which statins should be taken at night?

Answer 4

lovastatin, simvastatin, fluvastatin

Question 5

Which statins can be taken anytime?

Answer 5

atorvastatin, rosuvastatin, and pravastatin

Question 6

What are some toxicities of statins?

Answer 6

Birth defects (class X), hepatotoxicity (particularly in patients with underlying disease or chronic alcohol use), myopathy (low baseline risk but increases with dose, age, hepatic and renal function, and other drug interactions). Myopathy can progress to rhabdomyolosis

Question 7

Phase 1 CYP2C19 metabolizes which statins?

Answer 7

Fluvastatin and rosuvastatin

Question 8

Phase 1 CYP3A4 metabolizes which statins?

Answer 8

Lovastatin, simvastatin, and atorvastatin

Question 9

Phase 2 sulfation metabolizes which statin?

Answer 9

pravastatin

Question 10

What are some drugs that inhibit CYP3A4 and therefore increase risk of myopathy with concomittant use of statins?

Answer 10

Gemfibrozil (anticholesterol), amlodipine, warfarin, macrolides, azoles, digoxin, cyclosporin

Question 11

Simvastatin dose should not exceed what amount with amlodipine?

Answer 11

20mg/day

Question 12

Bile acid binding agents help decrease cholesterol by what mechanism?

Answer 12

They increase elimination of bile acids, drawing more cholesterol out of liver and eliminates them rather than being reabsorbed as cholesterol

Question 13

True or false: Colestipol enters the blood stream

Answer 13

False, it only remains in the GI tract

Question 14

BABA drugs are a decent alternate to what drug class during pregnancy

Answer 14

statins, but can be used alongside with statins

Question 15

What are some issues with BABA drugs?

Answer 15

• They have high doses (grams) which can lead to GI toxicities like dyspepsia, flatulence/bloating, diarrhea/constipation
• They also reduce absorption of numerous other drugs

Question 16

When should you take your medications while on BABA agents?

Answer 16

1 hour before or 3 hours after BABA administration

Question 17

Statins and BABA agents together can bring LDL down by what percent?

Answer 17

40-60%

Question 18

Statins have what effect on LDL, TG, and HDL

Answer 18

Decreases LDL and TG; no effect on HDL

Question 19

BABA agents have what effect on LDL, TG, and HDL

Answer 19

Decreases LDL, No effect on TG, Increases HDL minimally

Question 20

True or false: daily vitamins of niacin provide adequate amount

Answer 20

False, they provide little niacin

Question 21

What is the mechanism of action of Niacin?

Answer 21

Inhibits the synthesis of TGs in the liver

Question 22

What are the toxicities of Niacin?

Answer 22

Common, not serious: Flushing/pruitis

Serious, not common: Hepatotoxicity, insulin resistance (use cautiously in DM)

Question 23

Niacin has what effect on LDL, TG, and HDL

Answer 23

Decreases LDL and TG. Increases HDL (does more so than others)

Question 24

Fibric acid derivatives have what mechanisms of action in lowering cholesterol?

Answer 24

• Increases LDL receptor expression in hepatocytes, promoting sucking up of free cholesterol
• Activate Lipoprotein Lipase, therefore breaking down TGs
• Promotes oxidation of FFAs downstream

Question 25

What are some Fibric Acid toxicities/drug interactions?

Answer 25

• Myopathy (5%) when used with statins as fibric acid deriviatives Inhibit statin absorption into liver leading to increased serum statin and potentially myopathy
• Fibric acid derivatives bind to albumin and when used concomitantly with warfarin, warfarin can get kicked off albumin leading to free warfarin in blood increasing bleeding risk

Question 26

Fibric acid derivatives have what effects on LDL, TG, and HDL

Answer 26

Decreases LDL (but is variable on type of dyslipidemia), Decreases TG, and Increases HDL

Question 27

Ezetimibe has what mechanism of action when it comes to cholesterol?

Answer 27

Blocks absorption of cholesterol from intestines (NPC1 cholesterol receptor inhibitor) and therefore stimulates LDL-R expression

Question 28

Inhibition of ezetimibe increases synthesis of cholesterol, however. What drug can be combined with ezetimibe to inhibit this production?

Answer 28

Statins

Question 29

Ezetimibe has what effects on LDL, TG, and HDL

Answer 29

Decreases LDL, No effect on TG and HDL

Question 30

Alirocumab and Evolocumab have what mechanism of action when it comes to cholesterol?

Answer 30

They are antibody drugs that inhibit PCSK9. PCSK9 is a protein that induces LDL-R degradation. These antibody drugs therefore increase number of LDL-R on hepatocytes

Question 31

PCSK9 inhibitors have what effect on LDL, TG, and HDL

Answer 31

Decrease LDL. No effect on TG or HDL