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Textbook
Introduction
1. Anatomy
2. Microbiology
3. Physiology
4. Pathology
5. Pharmacology
5.1 Pharmacokinetics
5.2 Pharmacodynamics
5.3 Receptors, agonists and antagonists
5.4 Types of drug receptors
5.5 Anti-neoplastic drugs
5.6 Adverse effects of chemotherapeutic drugs
5.7 Newer chemotherapeutic drugs
5.8 Important drugs of the cardiovascular system
5.8.1 Drugs affecting coagulation
5.8.2 Drugs used in the treatment of hypertension
5.8.3 Anti-anginal drugs
5.8.4 Antiarrhythmics
5.8.5 Lipid lowering agents
5.8.6 Miscellaneous
5.9 Antimicrobials
5.10 Drugs acting on the renal system
5.11 Drugs acting on the respiratory system
5.12 Drugs acting on the gastrointestinal system
5.13 Antidiabetics and insulin
5.14 Miscellaneous
5.15 Additional information
6. Immunology
7. Biochemistry
8. Cell and molecular biology
9. Biostatistics and epidemiology
10. Genetics
11. Behavioral science
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5.8.5 Lipid lowering agents
Achievable USMLE/1
5. Pharmacology
5.8. Important drugs of the cardiovascular system

Lipid lowering agents

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Lipid lowering agents

Drug Mechanism of action Adverse effect Indication
Hydroxymethyl-glut-aryl coenzyme A (HMG CoA) reductase inhibitors: statins such as atorvastatin, lovastatin, rosuvastatin, simvastatin, etc. Decrease cholesterol synthesis by inhibiting the rate-limiting enzyme in cholesterol synthesis. This indirectly activates SREBP 2*, which increases LDL receptor expression on the cell surface and increases cellular uptake of LDL. Myalgia, myopathy, increased creatine kinase, myositis, rhabdomyolysis, hepatotoxicity, elevated liver enzymes; combining a statin with gemfibrozil or niacin increases the risk of severe myopathy. Lower LDL; lower triglycerides; raise HDL
Ezetimibe Inhibits NPC1L1 (Niemann-Pick C1-like 1), an intestinal protein that promotes cholesterol absorption. Elevated liver enzymes, diarrhea Lower LDL
Fibrates: gemfibrozil, fenofibrate Activate PPAR** alpha, which increases oxidation of free fatty acids, decreases hepatic triglyceride synthesis, and increases expression of lipoprotein lipase. Myopathy, cholesterol gallstones Lower triglycerides; increase HDL; lower LDL
Bile acid sequestrants/resins: cholestyramine, colestipol Prevent enterohepatic recycling of bile acids. This increases hepatic use of cholesterol to form bile acids, which decreases serum cholesterol levels and increases LDL receptor synthesis. Nausea, GI upset, decreased absorption of drugs and fat-soluble vitamins Lower LDL
Niacin (vitamin B3) Inhibits release of fatty acids from adipose tissue, decreases hepatic uptake of fatty acids, and decreases hepatic triglyceride synthesis. Skin flushing, dizziness, hypotension, tachycardia, itching, gout, diarrhea, hyperglycemia/diabetes, liver damage; flushing occurs due to increased arachidonic acid and prostaglandin D2 and E2 with cutaneous vasodilation. Aspirin taken 30 minutes before niacin prevents flushing. Lower triglycerides; lower LDL; increase HDL
Omega three fatty acids Decrease hepatic synthesis and secretion of VLDL; increase activity of lipoprotein lipase; decrease lipogenesis; anti-inflammatory. Headache, nausea, diarrhea, heartburn, bleeding tendency if used with anticoagulants Lower triglycerides
PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors: evolocumab and alirocumab (monoclonal antibodies to PCSK9) Inhibit PCSK9, an enzyme that degrades LDL receptors. Myalgia, delirium, dementia Lower LDL; lower triglycerides; increase HDL
Inhibitors of apolipoprotein B synthesis: mipomersen Inhibits Apo B synthesis in the liver. Injection site reactions, flu-like syndrome, headache, elevation of liver enzymes Lower LDL; lower VLDL; lower Lp(a)
Inhibitors of microsomal triglyceride transfer protein (MTP): lomitapide Binds to and inhibits MTP, preventing transfer of triglycerides to Apo B. Nausea, gastrointestinal upset, elevation of liver enzymes Lower LDL, especially in patients who lack LDL receptors

*SREBP 2 is sterol regulatory element binding protein

**PPAR alpha is peroxisome proliferator activated receptor alpha

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