3.2 Cholesterol Pharmacology Flashcards
What is the relationship between cholesterol and CHD risk?
Positive
What is the primary target to prevent CHD?
LDL cholesterol
What are the pro-atherogenic effects of Ox-LDL?
Inhibits macrophage motility
Induces T cell activation and VSMC division
Toxic to endothelial cells
Enhances platelet aggregation
Effect of obesity on cholesterol, triglycerides and HDL cholesterol
Cholesterol and triglycerides increase
HDL cholesterol decrease
What do statins do?
Inhibit cholesterol synthesis in hepatocytes
Increase clearance of IDL and LDL
Decrease production of VLDL and LDL
What enzyme do statins block?
HMG-CoA reductase
What are the indications for statins?
CV risk prevention
Familial hypercholesterolaemia
What is a mechanism of action of statins?
Increased synthesis of LDL receptor
Decreases serum cholesterol
What are some ADRs of statins?
Liver function - Increased transaminase levels
Muscle - Myopathy, diffuse muscle pain
Can sometimes have elevated CK can lead to rhabdomyolysis
Seen when statins used in higher doses and in combination with cyclosporin, gemfibrozil and erythromycin and niacin
GI complaints, arthralgias and headaches
What are some secondary benefits of statin treatment?
Anti-inflammatory
Plaque reduction
Improved endothelial cell function
Reduced thrombotic risk
What is a problem with cerivastatin?
Its structure caused drug-drug interaction
What is the receptor that fibrates act on?
Peroxisome Proliferator-Activated Receptor agonist
Increases production of lipoprotein lipase
What do fibrates do?
Reduces triglyceride production
Some reduction in LDL, may increase HDL
What is the mechanism of action of fibrates?
Increases fatty acid uptake and oxidation
Reduces triglyceride levels
Increases LDL particle size and HDL-C levels
Direct vascular effects
What are the indications for fibrates?
Adjunctive therapy to diet
Hypertriglyceridmia