7. Cholesterol Flashcards
What are the pro-atherogenic effects of Ox-LDL?
Inhibit macrophage motility, induce T cell activation, toxic to endothelial cells, enhances platelet aggregation.
What are the classes of lipid lowering drugs?
Statins, cholesterol lipase inhibitors, nicotinic acid/niacin, fibrates, resins, omega-3 fatty acids.
What is the action of statins?
Inhibit cholesterol synthesis in hepatocytes, increase clearance of IDL and LDL, decrease production of VLDL and LDL.
What is the mechanism of action of statins?
Blocks HMG-CoA reductase, increases LDL receptor synthesis.
What are the indications for use of statins?
CV risk prevention (CVD or diabetes), familial hypercholesterolaemia.
What are some of the ADRs of statins?
Increased transaminase levels (reversible and no evidence of liver disease), myopathy (muscle pain and CPK high, usually in higher doses), GI complaints, arthralgia, headaches.
What are some secondary benefits of statin treatment?
Anti-inflammatory, plaque reduction, improved endothelial cell function, reduced thrombotic risk.
What are fibric acid derivatives? (Structure).
Amphipathic carboxylic acids.
What receptors do fibric acid derivatives act on?
PPARa - peroxisome proliferator-activated receptor as an agonist.
What is the action of fibric acid derivatives?
Increased production of lipoprotein lipase - reduced triglyceride production, improved postprandial triglyceridaemia.
What is the mechanism of action of fibric acid derivatives?
Increased fatty acid uptake and oxidation, reduced TAGs levels, increased LDL size and HDL-C levels, vascular effects.
What are the indications for fibric acid derivatives use?
Adjunctive therapy to diet, hypertriglyceridemia, combined hyperlipidemia with low HDL who don’t respond to nicotinic acid.
How efficacious are fibric acid derivatives?
Decrease TAG 25-50%, LDL decreases but variable, increased HDL 15-25% in hypertriglyceridemia.
What are some ADRs of fibric acid derivatives?
GI upset, cholelithiasis, myositis, abnormal LFTs.
What are some contraindication for fibric acid derivative use?
Hepatic or renal dysfunction, pre-existing gallbladder disease.
What are the effects of nicotinic acid?
Reduce VLDL and increase HDL (high dose).
What is the mechanism of action of nicotinic acid?
Inhibits lipoprotein a synthesis and raises HDL-C.
What are the ADRs of nicotinic acid?
Flushing, itching, headache, hepatotoxicity, GI upset, activation of peptic ulcer, hyperglycaemia and reduced insulin sensitivity.
What are the contraindications of nicotinic acid use?
Active liver disease of LFT elevations, peptic ulcer disease.
What is the mechanism of action of ezetimibe?
Selectively inhibits intestinal cholesterol absorption so decreased delivery to liver, more LDL receptors expressed and reduced cholesterol in atherogenic particles.
What are the ADRs of ezetimibe?
Headache, abdominal pain, diarrhoea.
What should be considered in combination therapy for cholesterol lowering drugs?
Benefit in terms of CV risk reduction, cost, and ADRs.
What are the benefits of combining fibrates and statins as therapy to lower cholesterol?
Improve TAG, LDL-C, and HDL-C levels.
What are the risks associated with combining fibrates and statins?
Myopathy and rhabdomyolysis.
What are the positive additions to diet that may help cholesterol levels?
Fish oils, fibre, vitamin C/E, alcohol (increased HDL), plant sterols.
What are the negative additions to diet that may worsen cholesterol levels?
Dietary cholesterol/fat, alcohol.
