1. Treatment options for dyslipedemia
1.1. Cholesterol absorption inhibitors
1.1.1. Examples
1.1.1.1. Ezetimibe
1.1.1.1.1. azetidinone cholesterol absorption inhibitors
1.1.2. MOA
1.1.2.1. inhibits absorption of cholesterol (and of plant stanols)
1.1.2.1.1. Block NPC1L1 in brush border of enterocytes
1.1.3. Adverse effect
1.1.3.1. Diarrhoa
1.1.3.2. Abdominal pain
1.1.3.3. Headache
1.1.3.4. Myalgia (muscle damage)
1.2. Statins/HMG-CoA reductase inhibitors
1.2.1. Examples
1.2.1.1. Pitavastatin
1.2.1.2. Atorvastatin
1.2.1.3. Simvastatin
1.2.1.4. Rosuvastatin
1.2.2. MOA
1.2.2.1. Inhibits HMG-CoA reductase
1.2.2.1.1. Decrease cholesterol synthesis & up-regulate LDL receptors on hepatocytes; decrease VLDL secretion
1.2.3. Adverse effects
1.2.3.1. Myopathy
1.2.3.2. Rhabdomyolysis
1.2.3.3. Raised liver enzymes
1.2.3.4. Jaundice
1.3. Bile Acid Sequestrants (BAS)
1.3.1. Example
1.3.1.1. Colestipol
1.3.2. MOA
1.3.2.1. Binds to bile acids in gut, prevents reabsorption.
1.3.2.1.1. Increase cholesterol catabolism, up-regulates LDL receptors
1.3.3. Adverse effects
1.3.3.1. Constipation
1.3.3.2. Diarrhea
1.3.3.3. Hypertiglyceridemia
1.4. PCSK9 Inhibitors
1.4.1. Example
1.4.1.1. Alirocumab
1.4.1.2. Evolocumab
1.4.2. MOA
1.4.2.1. PCSK9 protein bind to LDL receptor in liver --> endocytosis --> degradation of LDL( instead of being recycled) in lysosomes
1.4.2.1.1. PCSK9 inhibitor bind to PCSK9 protein --> PCSK9 cannot bind to LDL receptor --> more LDL receptor on cell surface --> increase LDL uptake --> LDL levels reduced
1.5. Omega 3 Fatty Acids
1.5.1. MOA: Reduce production of VLDL & increase VLDL clearance -> reduce triglycerides levels
1.5.1.1. Reduce ischaemic heart disease & improves survival in myocardial infarction patients
1.5.2. Can also inhibit platelet function & prolong bleeding + anti-inflammatory effects & decrease plasma fibrinogen
1.5.3. Omega 3 acid ethyl esters
1.5.3.1. combination of Omega 3 Fatty acids + ethanol
1.5.3.1.1. Prevention of recurrent events after myocardial infarction + treatment of hypertriglyceridaemia
1.5.3.1.2. Less increase in LDL & less problems with fishy odour, weight gain & dyspepsia than the older fish oil preparations
1.5.4. Some convert VLDL -> IDL which increases LDL -> cholesterol levels may increase
1.6. Fibrates
1.6.1. MOA: Reduces circulating LDL
1.6.1.1. increased hepatic LDL uptake
1.6.1.2. decreased transcription of the genes for apoC2, apoC3
1.6.1.2.1. decrease VLDL
1.6.1.3. increased transcription of the genes that codes for
1.6.1.3.1. lipoprotein lipase
1.6.1.3.2. apoA1 and apoA2
1.6.2. Agonists at PPARα nuclear receptors
1.6.3. Reduces plasma C-reactive protein and fibrinogen
1.6.4. Improves glucose tolerance
1.6.5. Inhibits vascular smooth muscle inflammation
1.6.6. Examples
1.6.6.1. Fenofibrate
1.6.6.2. Gemfibrozil
1.6.7. Adverse Effects
1.6.7.1. Raised liver enzymes
1.6.7.2. Myopathy
1.6.7.3. Lithiasis
2. Hypercholesterolemia
2.1. Statin
2.1.1. add ezetimibe if lipids still not at target
3. Mixed Dyslipidaemia
3.1. Total Cholesterol > 6.2mmol/L
3.2. LDL Cholesterol >3.4 mmol/L
3.3. Statin
3.3.1. add ezetimibe if lipids still not at target
3.4. Fibrate
3.4.1. add Niacin if lipids still not at target
4. Hypertriglyceridemia
4.1. > 4.5 mmol/L or 400mg/dL
4.2. Fibrate
4.3. Omega Fatty 3 Acids
4.3.1. if triglyceride > 4.5 mmol/L or 400 mg/dL