Lipid Metabolism and Pharmacology Quiz

Lipid Lowering Drugs

•  Lipid lowering drugs are used to treat conditions like atherosclerosis and hyperlipidemia.
•  Atherosclerosis is a condition where plaque builds up in arteries, which can lead to heart attack or stroke.
•  Hyperlipidemia is high lipid levels in the blood, including cholesterol and triglycerides.
•  Drugs to lower lipids include statins, fibrates, drugs that inhibit cholesterol absorption, nicotinic acid and fish oil derivatives.

Lipoprotein Metabolism and Dyslipidemia

•  Cholesterol and triglycerides are transported in the blood as lipoproteins.
•  There are four main classes of lipoproteins: HDL, LDL, VLDL and Chylomicrons.
•  HDL: High-density lipoproteins (contain apoA1 and apoA2)
•  LDL: Low-density lipoproteins (contain apoB-100)
•  VLDL: Very-low-density lipoprotein particles (contain apoB-100)
•  Chylomicrons: Contain apoB-48
•  High levels of LDL and lower levels of HDL cholesterol correlate with a higher risk of heart disease.

Cholesterol Metabolism

•  Cholesterol is produced endogenously by the liver (internal cholesterol production) and exogenously from diet.
•  Endogenous cholesterol production occurs via the HMG-CoA reductase enzyme pathway in hepatocytes.
• Dietary cholesterol is absorbed in the intestine with the help of NPC1L1 proteins.
• Bile acids aid digestion and transport of dietary fats and cholesterol.
•  LDL transports cholesterol to tissues; excess LDL is collected by the liver.
• HDL collects cholesterol from tissues and returns it to the liver.
• CETP transfers cholesterol esters between HDL and LDL.

Atheromatous Disease

•  Atheroma (atherosclerosis) is a condition where lipids (cholesterol, proteins, etc.) build up inside arteries compromising blood flow.
•  Atheromas are dangerous as they can lead to issues such as heart attacks, coronary artery disease, peripheral artery disease and stroke.
•  High levels of LDL and lower levels of HDL cholesterol contribute to atherosclerosis.
• Risk factors such as diabetes, dyslipidemia, and smoking cause endothelial dysfunction, which promotes the development of atherosclerosis.
• Healthy endothelium produces nitric oxide to protect blood vessels and maintain dilation, reducing risk of inflammation.
• Treatments like statins, PCSK9 inhibitors, and lifestyle improvements can slow down or prevent atherosclerosis progression.

Drug Treatments (STATINS)

•  Statins, like simvastatin, atorvastatin, and rosuvastatin, are HMG-CoA reductase inhibitors.
•  They specifically, reversibly and competitively inhibit HMG-CoA reductase, a key enzyme in cholesterol production.
•  Statins increase LDL receptors and cholesterol associated with HDL.
•  They reduce plasma LDL cholesterol.
•  Side effects (ADRs) can include myalgia (muscle pain), raised liver enzymes, insomnia, rash and more serious cases like skeletal muscle damage and hepatotoxicity.
•  Statin therapy is associated with a modest increase in the incidence of type 2 diabetes mellitus.
•  Statins are primarily used for primary and secondary prevention of arterial disease.
•  They can lower serum cholesterol in homozygous familial hypercholesterolaemia.
•  In severe drug-resistant hyperlipidemia, combined treatments (with ezetimibe, which inhibits cholesterol absorption, is often used) may be necessary.
• Short-acting statins are generally administered orally at night for optimal effectiveness.
• They are well absorbed by the liver.
• First pass effect may occur.

Drug Treatments (FIBRATES)

•  Gemfibrozil and fenofibrate are agonists at PPARα nuclear receptors.
•  These drugs regulate the expression of genes for lipoprotein lipases.
•  They markedly reduce circulating VLDL and triglycerides, also increase lipoprotein lipase activity and LDL uptake.
•  Rhabdomyolysis is associated with fibrate use, especially in patients with renal impairment or combined with statins.
•  Liver and kidney function must be assessed due to the risk of adverse reactions.
•  Fibrates, and combinations if needed, can be used for mixed dyslipidemia and severe hypertriglyceridemia in patients that haven't responded to other measures.

Drug Treatments (Bile Acid Binding Resins)

•  Bile acid-binding resins, like colestyramine, colestipol, and colesevelam, sequester bile acids in the intestine.
•  This prevents bile acid reabsorption, forcing the liver to use more cholesterol to produce more bile acids.
•  They reduce circulating LDL and cholesterol levels.
•  Side effects often include diarrhea.

Drug Treatments (Ezetimibe)

•  Ezetimibe blocks the transport protein NPC1L1, preventing cholesterol absorption in the intestines This prevents cholesterol from entering the bloodstream.
•  Often used in combination with statins
•  Reduces cholesterol levels by lowering intestinal cholesterol absorption.
•  Generally used as an additional agent when statin treatment response is insufficient.

Novel Drug Treatments (Bempedoic Acid)

•  Bempedoic acid is an inhibitor of ATP-citrate lyase.
•  This enzyme is upstream of HMG-CoA reductase in cholesterol synthesis.
•  Bempedoic acid causes further cholesterol reduction in patients already taking maximal statin doses.
•  Gout is a significant side effect. (hyperuricemia)

Novel Drug Treatments (PCSK9 Inhibitors)

•  PCSK9 inhibitors (evolocumab and alirocumab) inhibit PCSK9, a protein that breaks down LDL receptors.
•  Blocking PCSK9 increases LDL receptor availability for lipid clearance.
•  These are often used when other treatments do not adequately manage LDL.

Drug Treatments (Lomitipide)

•  Lomitipide inhibits the microsomal triglyceride transfer protein (MTP).
•  MTP is involved in loading triglycerides onto apolipoprotein B100 in lipoprotein formation. -Lomitipide reduce hepatic lipoprotein secretion and can be an additional agent in treatment of homozygous FH.

Clinical Uses (general)

•  Lipid-lowering drugs may be used for primary/secondary prevention of various cardiovascular events, when other risk factors exist, to treat severe hyperlipidemia, or in conjunction with other treatments when additional lipid lowering is needed.

Test your knowledge on lipid metabolism, lipoproteins, and the pharmacological agents affecting cholesterol levels, like bempedoic acid and PCSK9 inhibitors. This quiz covers the mechanisms of action, clinical uses, and health implications of various lipid-related compounds and processes.