Anti-dyslipidemic agents

Question 1

What is hyperlipidemia?

Answer 1

It means that there are elevated levels of triglycerides and cholesterol, and reduced levels of HDL-C levels, this might be due to genetic, lifestyle, or metabolism like diabetes mellitus

Question 2

What is the goal when treating hyperlipidemia?

Answer 2

To lower the levels of LDL and VLDL, and increase the levels of HDL in order to prevent the buildup of atherosclerotic plaque

Question 3

What are the examples of lipid-modifying drugs?

Answer 3

1) Statins (most effective)

2) Bile acid sequestrants (resins)

3) Fibrates

4) Nicotinic acid

5) Non-prescription agents (plants sterols)

6) Agents reducing the absorption of cholesterol from the intestine (Ezetimibe)

• Combination of these groups might be used

Question 4

What is the mechanism of action of statins?

Answer 4

They inhibit the activity of the HMG-CoA reductase enzyme, reducing the endogenous synthesis of cholesterol and increasing LDL receptors in the liver

• They are effective in reducing cholesterol levels in both familial and non-familial hypercholesterolemia
• They also have a weak anti-inflammatory activity improving the endothelial function

Question 5

What are the adverse effects of statins?

Answer 5

1) Nausea, epigastric fullness, constipation, headache

2) Mild elevation of transaminases

3) Myositis, rhabdomyolysis and myoglobinuria

4) Hypotension

Question 5

What are the examples of drugs that are considered statins?

Answer 5

1) Lovastatin

2) Simvastatin

3) Pravastatin

4) Atorvastatin

5) Fluvastatin

Question 6

what are the clinical effects of statins?

Answer 6

1) Reduces LDL cholesterol by 20-60%

2) Reduces plasma triglycerides by 10-30%

3) HDL cholesterol increases by 5-15%

Question 7

What is the mechanism of action of bile acid sequestrants?

Answer 7

They release chloride ions which bind to bile acids resulting in a bile acid complex that cannot be absorbed and the bile acids are excreted in the feces preventing the reutilization of the bile acids which will force the liver to synthesize more bile acids from cholesterol

Question 8

What are the different drugs of bile acid sequestrants?

Answer 8

1) Cholestyramine (Questran)

2) Colestipol (Colestid)

3) Colesevelam (Colesevelam)

Question 9

What are the adverse effects of bile acid sequestrants (cholestyramine, colestipol)

Answer 9

1) Constipation, heartburn, abdominal pain, nausea

2) Impairs the absorption of fat-soluble vitamins (D, A, K, E) and other substances like IRON & FOLATE

3) They bind with other fat-soluble drugs and weak acidic drugs like naproxen and thiazide diuretics

Question 10

What are the examples of fibrates drugs?

Answer 10

1) Gemfibrozil

2) Clofibrate

3) Bezafibrate

4) Fenofibrate

Question 11

What is the mechanism of action of fibrates?

Answer 11

1) They stimulate the activity of peroxisome proliferating activating receptors (PPARa), where the activation of those genes alters the transcription of genes involved in the triglyceride metabolism, by:

1) stimulating lipoprotein lipase (increases the clearance of TGs)

2) Increases the production of Apo-A-1 (Increases HDL)

3) Decreases Apo-C3 “lipoprotein lipase inhibitor” (decreases the clearance of VLDL)

• It also increases the oxidation of fatty acids in the liver

Question 12

What are the therapeutic uses of fibrates?

Answer 12

Dysbetalipoproteinema (Type-3)

Question 13

What are the adverse effects of fibrates?

Answer 13

1) Fenofibrate produces cholelithiasis and cholecystitis (inflammation of the gallbladder which could be life-threatening)

2) Abdominal discomfort

3) Slightly elevates liver enzymes

4) Muscle tenderness with raised serum creatine kinase

Question 14

What is the mechanism of action of nicotinic acid (Niacin, Vitamin B3)

Answer 14

1. It is a water soluble vitamin
2. It reduces the production of VLDL in the liver and thus lowering the LDL levels (Reduces plasma VLDL via the inhibition of the synthesis of fatty acids in the liver)
3. Reduced lipolysis from the adipose tissue by inhibiting adipose tissue lipase (decreasing the plasma levels of fatty acids and triglycerides)

⁃ nicotinic acid at high doses can lower the levels of triglycerides and cholesterol but it’s different when it’s converted to nicotinamide the vitamin used in the biosynthesis of NAD and NADP

⁃ In small doses nicotinic acid is used a vitamin B3 supplement to treat pellagra

Question 15

What are the clinical effects of niacin?

Answer 15

1. At high doses (1.5-3 grams) it affects all plasma lipid subtypes reducing the plasma LDL by 10-25%, TGs by 5-30%, and increases HDL by 10-20%

Question 16

When is niacin contraindicated?

Answer 16

1) In diabetes (reduces insulin sensitivity)
2) gout (it increases uric acid)

Question 17

What are the Adverse effects of niacin?

Answer 17

1. Flushing, tingling, headache (PG induced, give aspirin to reduce sensitivity and this side effects as it inhibits Cox2)
2. Nausea, diarrhea
3. Contraindicated in gouts and diabetes as it induces insulin resistance
4. Hepatotoxicity
5. Reversible effects on the liver
6. Niacin can also inhibit PGs, increasing gastric acids which could lead to peptic ulcers

Question 18

What is mechanism of action of ezetimibe (zetia)?

Answer 18

1. Acts in the intestine reducing cholesterol absorption, which in return will cause less production of VLDL and thus LDL
2. Blocks cholesterol transport
3. When used alone it reduces the plasma cholesterol by 18% and 10% in TGs
4. When combined with a statin it reduces the cholesterol level up to 72%

Question 19

What are the adverse effects of ezetimibe?

Answer 19

It is well tolerated and the only side effects are fatigue, abdominal pain, and diarrhea

Question 20

Which drug is the most effective in reducing the levels of TGs and LDL together?

Answer 20

Statins, reducing it by 20-60%

Question 21

Which drug is most effective in reducing the levels of triglycerides mainly?

Answer 21

1. Fibric acid derivatives 20-50%
2. Niacin 20-50%

Question 22

Which drug is most effective in increasing the levels of HDL?

Answer 22

Niacin 15-35%

Question 23

Bile acid sequestrants are most effective in reducing which hyperlipidemia?

Answer 23

TG and LDL by 10-30%

Question 24

What is the mechanism of action of (protein convertase subtitlisn/Kexin type 9) PCSK9 inhibitor?

Answer 24

PCSK9 degrades the LDL receptor in the liver inhibiting it and increasing the LDL receptors which will reduce the levels of cholesterol in the blood like evolocumab and alirocumab

Question 25

What is the role of omega-3 FA in the treatment of hyperlipidemia?

Answer 25

They improve CVS health by lowering the levels of TGs and the chances of atherosclerosis, they also increase the levels of HDL, & lower the inflammatory response via increasing the expression of LDL receptors and increasing the beta-oxidation of the TGs