8) Cholesterol Flashcards
Describe the process of atheroma formation:
Endothelial dysfunction
Infiltration and entrapment of LDLs in arterial wall
LDL oxidation causes SMC proliferation and T cell activation
Formation of fibrous cap
What are some risk factors for atheroma development:
High BP, smoking, high cholesterol
What should normal cholesterol be?
<5mmol/L
Name some classes of lipid lowering drugs:
Statins Cholesterol lipase inhibitors Fibrates Nicotinic acid Resins Omega 3 fatty acids Plant sterols
What is the mechanism of action of statins?
HMG-CoA reductase inhibitors
When are statins prescribed?
Cardiovascular risk prevention and familial hypercholesterolemia
What are some side effects of statins?
Increased transaminase levels
Myopathy
GI issues, arthralgias, headaches
How can statins be monitored?
LFTs and creatine kinase
What are some secondary benefits of statins?
Anti-inflammatory
Plaque reduction
Improved endothelial function
Decreased thrombotic risk
Describe the pharmacokinetics of statins:
Extensive hepatic first pass metabolism
Eliminated by liver
Name one short acting and one long acting statin:
Simvastatin is short acting
Atorvastatin is long acting
What are fibrates and when are they used?
Ampipathic carboxylic acids
Used in hypertriglyceridemia
What is the mechanism of action of fibrates?
Peroxisome proliferator-activated receptor agonist - increase production of lipoprotein lipase
What are the side effects of fibrates?
GI upset, cholelithiasis, myositis, abnormal LFTs
When are fibrates contraindicated?
Hepatic/renal dysfunction
Previous gallbladder disease
What effects does nicotinic acid have on lipid profile?
Reduces VLDL and increases HDL
What are the side effects of nicotinic acid?
Flushing, itching, headache (give with aspirin)
Hepatotoxicity
Peptic ulcers
Hyperglycemia, decreased insulin sensitivity
When is nicotinic acid contraindicated?
Liver disease
Peptic ulcer disease
What is the mechanism of action of the cholesterol absorption inhibitor, Ezetimibe?
Blocks cholesterol transport protein NPC1L1 in brush border so less cholesterol to liver
How are the systemic side effects of ezetimibe reduced?
Enterohepatic circulation
What are the side effects of ezetimibe?
Headache
Abdominal pain
Diarrhoea
What combination therapies can be used in lipid lowering?
Statin and fibrate/nicotinic acid/ezetimbe
Why does extra care need to be taken when combining fibrates and statins?
Increased risk of myopathy and rhabdomyolysis
How do plant sterols reduce cholesterol?
Compete with cholesterol for absorption
What are some dietary factors that can reduce cholesterol?
Fish oil, fibre, vit C/E, alcohol (HDL)
After CHD assessment, who is offered atorvastatin?
Those with 10% or greater 10 year risk of CHD
