Untitled Quiz

Hyperlipidemia

• Elevated levels of circulating lipids, specifically cholesterol and triglycerides (TG)
• Correlated with an increased incidence of atherosclerosis and coronary artery disease (CAD)

Factors Influencing Hyperlipidemia

• Age
• Sex
• Family history
• Smoking
• Alcoholic
• Hypertension
• Diabetes
• Obesity
• Low HDL levels

Treatment of Hyperlipidemia

• Non-Pharmacological Therapy (First Line)
  • Diet modification:
    • Decrease intake of total fat and especially saturated fat
    • Increase fiber intake
    • Increase Omega-3-fatty acids (found in fish)
    • Increase fruits and vegetables (antioxidants)
    • Decrease simple sugars (sucrose)
  • Exercise (↑ HDL levels)

Antihyperlipidemic Drugs

• Statins
• Niacin
• Fibrates
• Bile acid sequestrants
• Cholesterol absorption inhibitors
• Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors

Statins

• Competitive inhibitor of HMG CoA reductase, the rate-limiting step in cholesterol synthesis
• Reduce hepatic cholesterol, resulting in:
  • Increased LDL receptor expression
  • Increased removal of LDL-C from the blood
  • Decreased cholesterol synthesis
  • Decreased VLDL synthesis and secretion
• Side effects:
  • Elevated liver enzymes
  • Myopathy and rhabdomyolysis
  • Enzyme CYP-3A4 interaction
  • GIT disturbance
  • Contra-indicated in pregnancy
• Indications:
  • Used in hypercholesterolemia
  • Used in Coronary Artery Disease (CAD)
  • Used in patients with triglycerides levels higher than 250 mg/dL and with reduced HDL-C levels

Niacin (Nicotinic acid)

• Inhibits lipolysis in adipose tissue, resulting in:
  • Decreased hepatic VLDL synthesis
  • Decreased production of LDL in the plasma
  • Decreased LDL and TG levels by 25 and 50%, respectively
  • Increased HDL by 35%
• Side effects:
  • Prostaglandin-mediated flushing and pruritus
  • Nausea and abdominal discomfort
  • Hyperuricemia and hepatotoxicity
• Indications:
  • Familial hyperlipidemia
  • Mixed elevation of LDL-C and TG (in combination with statins)
  • Elevation of TG (VLDL) and low levels of HDL

Fibrates (gemfibrozil and fenofibrate)

• Primarily used for reducing TG and increasing HDL serum levels
• Mechanism of action:
  • Activators of the nuclear transcription factor peroxisome proliferator-activated receptor α (PPARα)
  • Increased LPL expression
  • Increased TG clearance from circulating VLDL
  • Increased expression of HDL levels
• Side effects:
  • Mild GI disturbances
  • Gallstones (increased biliary cholesterol excretion)
  • Myalgia and rhabdomyolysis have been reported in patients taking gemfibrozil and statins together
  • Both fibrates may increase the effects of warfarin

Bile Acid Sequestrants (Cholestyramine, colestipol, and colesevelam)

• LDL-C lowering effects
• Mechanism of action:
  • Bind negatively charged bile acids and bile salts in the small intestine
  • Resin/bile acid complex is excreted in the feces
  • Lowering bile acid concentration leads to:
    • Increased conversion of cholesterol to bile acids
    • Increased hepatic uptake of cholesterol-containing LDL-C particles
    • Decrease in plasma LDL-C
• Indications:
  • Type IIA and type IIB hyperlipidemias
  • Cholestyramine can also relieve pruritus caused by biliary stasis
  • Colesevelam is also indicated for type 2 diabetes due to its glucose-lowering effects
• Side effects:
  • GI disturbances (constipation, nausea, and flatulence)
  • Impairment of absorption of fat-soluble vitamins (A, D, E, and K)
  • Interference with the absorption of many drugs (digoxin, warfarin, and thyroid hormone)

Inhibitors of Cholesterol Absorption (Ezetimibe)

• Mechanism of action:
  • Prevention of absorption of dietary cholesterol and cholesterol that is excreted in bile
  • Increased LDL receptors in liver and increased removal of LDL-C from the blood
• Indications:
  • Used in hypercholesterolemia
  • As monotherapy, ezetimibe reduces LDL-C by about 18%
  • When combined with a statin, it is even more effective
• Side effects:
  • Well tolerated

Proprotein Convertase Subtilisin Kexin Type 9 Inhibitors (Alirocumab and Evolocumab)

• Mechanism of action:
  • Inhibit the PCSK9 enzyme, leading to:
    • Increased LDL receptors on the surface of hepatocytes
    • Increased clearance of LDL-C from the serum
• Indications:
  • Used in addition to maximally tolerated statin therapy in patients with heterozygous or homozygous familial hypercholesterolemia
  • Clinical ASCVD who require additional LDL-C lowering

Fibrates

• Increase HDL by 35%
• Indications: Familial hyperlipidemia, Mixed elevation of LDL-C and TG, Elevation of TG and low levels of HDL
• Side effects: Prostaglandin-mediated flushing and pruritus, Nausea and abdominal discomfort, Hyperuricemia and hepatotoxicity
• Mechanism of action: Activators of PPARα, increase LPL expression, increase TG clearance from circulating VLDL, increase expression of HDL levels
• Adverse effects: Mild GI disturbances, Gallstones, Myalgia and rhabdomyolysis (with statins), Increased effects of warfarin

Bile Acid Sequestrants

• Mechanism of action: Bind negatively charged bile acids and bile salts in the small intestine, reduce bile acid concentration, increase conversion of cholesterol to bile acids
• Indications: High LDL-C, Statin intolerance
• Side effects: GI disturbances, Impaired absorption of fat-soluble vitamins (A, D, E, K), Interference with absorption of certain drugs

PCSK9 Inhibitors

• Mechanism of action: Inhibit PCSK9 enzyme, increase LDL receptors, increase clearance of LDL-C from serum
• Indications: Familial hypercholesterolemia, Clinical ASCVD, High ASCVD risk and statin intolerance
• Side effects: Injection site reactions, Immunologic or allergic reactions, Nasopharyngitis, Upper respiratory tract infections

Inhibitors of Cholesterol Absorption

• Mechanism of action: Prevent absorption of dietary cholesterol and cholesterol in bile, increase LDL receptors in liver, increase removal of LDL-C from blood
• Indications: Hypercholesterolemia
• Side effects: Well tolerated

Hyperlipidemia

• Hyperlipidemia is a condition characterized by elevated levels of circulating lipids, specifically cholesterol and triglycerides (TG).
• It is correlated with an increased incidence of atherosclerosis and coronary artery disease (CAD).

Risk Factors

• Age
• Sex
• Family history
• Smoking
• Alcoholic
• Hypertension
• Diabetes
• Obesity
• Low HDL levels

Treatment of Hyperlipidemia

Non-Pharmacological Therapy

• Diet modification:
  • Decrease intake of total fat and especially saturated fat
  • Increase fiber intake
  • Increase Omega-3-fatty acids (found in fish)
  • Increase fruits and vegetables (antioxidants)
  • Decrease simple sugars (sucrose)
• Exercise (increases HDL levels)

Pharmacological Therapy

Antihyperlipidemic Drugs

• 1. Statins
• 2. Niacin:
  • Increases HDL by 35%
  • Indications:
    • Familial hyperlipidemia
    • Mixed elevation of LDL-C and TG (in combination with statins)
    • Elevation of TG (VLDL) and low levels of HDL
  • Side effects:
    • Prostaglandin-mediated flushing and pruritus
    • Nausea and abdominal discomfort
    • Hyperuricemia and hepatotoxicity
• 3. Fibrates (gemfibrozil and fenofibrate):
  • Primarily used for reducing TG and increasing HDL serum levels
  • Mechanism of action: Activators of the nuclear transcription factor peroxisome proliferator-activated receptor α (PPARα)
  • Adverse Effects:
    • Mild GI disturbances
    • Gallstones (increase biliary cholesterol excretion)
    • Myalgia and rhabdomyolysis have been reported in patients taking gemfibrozil and statins together
• 4. Bile acid sequestrants (Cholestyramine, colestipol, and colesevelam):
  • Mechanism of action: Bind negatively charged bile acids and bile salts in the small intestine
  • Indications:
    • Type IIA and type IIB hyperlipidemias
    • Cholestyramine can also relieve pruritus caused by biliary stasis
    • Colesevelam is also indicated for type 2 diabetes due to its glucose-lowering effects
  • Side effects:
    • GI disturbances, such as constipation, nausea, and flatulence
    • Impair the absorption of the fat-soluble vitamins (A, D, E, and K)
• 5. Inhibitors of cholesterol absorption (Ezetimibe):
  • Mechanism of action: Prevention of absorption of dietary cholesterol and cholesterol that is excreted in bile
  • Indications:
    • Hypercholesterolemia
    • As monotherapy, ezetimibe reduces LDL-C by about 18%
    • When combined with a statin, it is even more effective
  • Side effects: Generally well-tolerated
• 6. Proprotein convertase subtilisin kexin type 9 inhibitors (Alirocumab and evolocumab):
  • Mechanism of action: Inhibit the PCSK9 enzyme, leading to an increase in LDL receptors on hepatocytes
  • Indications:
    • Used in addition to maximally tolerated statin therapy in patients with heterozygous or homozygous familial hypercholesterolemia
    • Clinical ASCVD who require additional LDL-C lowering