Cholesterol Flashcards
What is the impact of high cholesterol/LDLs on the body?
They are major risk factors for MI, CHD and stroke due to atherosclerosis involvement (see MoD/CVS notes)
What study showed a link between cholesterol/LDL and coronary atherosclerosis?
Framingham study
What are the normal total cholesterol, fasting LDL and HDL levels?
Total cholesterol - 5mmol/L or less
Fasting LDLs - 3mmol/L or less
HDLs - 1.2mmol/L or less
What foods are good for tackling high cholesterol?
Fish oils, fibre, vitamin C/E, alcohol (HDLs)
What foods are bad for cholesterol?
Dietary cholesterol/fat, alcohol (triglycerides)
Describe the mechanism of action for statins
Hepatocytes - inhibit HMG-CoA reductase which is required for the synthesis of cholesterol from acetyl-CoA. This leads to a reduction in plasma cholesterol and this increases LDL receptors (less internalised) and reduces plasma cholesterol further.
LDL levels fall, triglyceride levels fall, HDL levels increase
Describe the pharmacokinetics of statins stating some of the differences
Absorption varies and there is excessive hepatic first pass uptake so that only 5-30% reaches
Some metabolised by CYP3A4, others only phase II reactions
Simvastatin - half life of 1-4 hours, taken at night to match peak cholesterol production in the early morning
Atorvastatin and rosuvastatin - half life of 20 hours taken at any time of day
Are stating linear or non-linear?
Non-linear
What are the ADRs for statins?
Usually well tolerated
Increase in transminase levels
Myopathies and rhabdomyolysis - test CPK
What are the DDIs for statins?
CYP450 inducers decrease effect and inhibitors increase risk of ADR
What monitor is required for statin treatment?
LFTs, LDLs
What study showed reduced mortality taking statins?
4S Total Mortality
Name some other studies concerning statins
WOSCOPS - less non-fatal MI and CHD death
CARE - less non-fatal MI and CHD death
LIPID - reduced cumulative death from CHD
AFCAPS/TexCAPS - less non-fatal MI, sudden cardiac death and unstable angina
Name a cholesterol absorption inhibitor and when would it be used?
Ezetimibe - statin intolerance, or with statin can further reduce LDLs (better than increasing statin which increases risk of ADR)
What is the mechanism for cholesterol uptake inhibitors?
Block cholesterol transport protein NPC1L1 in the brush border thus reduces uptake of dietary cholesterol. This in turn increases LDL receptors and further reduces plasma cholesterol.
It circulates enterohepatically so can be recycled and limits systemic exposure.
What are the main ADRs of cholesterol uptake inhibitors?
Headache, abdominal pain, diarrhoea
What are the indications and contraindications for the use of fibrates?
Mainly used for hypertryglyceraemias but can be used in addition to statins (increased risk of myopathy and rhabdomyolysis)
Not to be used in renal dysfunction and gall bladder disease
What is the mechanism of fibrate drugs?
They stimulate PPAR-a which increases lipoprotein lipase which increases the uptake of fatty acids and reduces triglyceride production. Also lowers LDLs and raises HDLs.
What are the main ADRs of fibrates?
GI upset, gallstones, myositis, abnormal LFTs
What two studies looked at fibrate usage? What did they conclude?
BIP- reduced LDLs, triglycerides, increased LDLs, less non-fatal MI/CHD death in secondary prevention.
Helsinki heart study - less non-fatal MI/CHD death in primary prevention.
What are the contraindications for nicotinic acid? What is its mechanism of action? What are the main ADRs?
Contraindications - liver disease, unexplained raised LFTs, peptic ulcer.
Mechanism - inhibits lipoprotein a synthesis, reduces VLDL and increases HDL to reduce CHD.
ADRs - hepatotoxic, activation of peptic ulcer, hyperglycaemia, flushing, itching.
What are the 4 classes of drugs used to treat hyperlipidaemia?
Statins
Cholesterol uptake inhibitors
Fibrates
Nicotinic acid
