hyperlipidemias Flashcards
name 3 things that cholesterol makes / maintians
cell membrane integrity, steroid hormones, bile acids and Vit D
Outline the pathogenesis of Atherosclerosis
LDL oxidation = damage endothelium with monocytes (scavenger receptor) in the intima . Foam cells are made and SMC proliferate. Elastin and collagen form cap and central necrosis occurs. = fatty streak it has its own blood supply
what is the role of HDL ?
transport excess cholesterol from cells to liver for recycling
for every 1mmol/l of total cholesterol reduction =
20% decrease in risk CVD diease
when can fatty streaks start to from?
20+ years onwards
how do statins work ?
competitive inhibitor of HMG-CoA reductase (mevalonate pathway ) , rate controlling. low intracellular cholesterol leads to up-regulation of LDL receptors so increases clearance of LDL
Name 3 statins
Atorvastatin , simvastatin , Fluvastatin and Lovastatin
Name 3 additional benefits of statins
Improved endothelium - increase NO and VEGF, decrease Endothelin
Stabilise plaques - Decrease SMC proliferation , increased collagen
Improved haemostasis- decrease fibrinogen , platelets and increase fibrinolysis
decrease inflammation = less CRP
Antioxidant = Decreased superoxide
what is the half life of simvastatin and atrovastatin ?
Simvastatin - 2 hours, take at nigth
Atorvastatin - over 30 hours
what are some ADRs of statins?
slight LFT increase
low-level myalgia with amiodarone
Rhabomyololysis
GI disruption , nausea and headaches
what is NNT and what is the average NNT in statins?
NNT= Number needed to treat and is about 18 for statins which is quite low
what is NICE guidelines of Statins?
Artorvastatin
20mg for people with 10% risk of CHD
80mg daily for people with heart disease
why should you take simvastatin at night ?
low t1/2 , LDL receptor made at night due to circadian rhythm
How do fibrates work ?
Activation of transcription factors- PPAR alpha. increase Lipoprotein lipase = reduction in TAG in plasma
increase FA uptake in liver and LDL affinity for its
receptor
act at different site to statins
primary function = reduce TAG
Name 2 fibrates
Fenofibrate
ciprofribrate
gemfibrozil
name 3 side effects of fibrates
when should you not use firbates ?
Upset GI, Gall stones, myositis, abnormal LFTs, warfarin inducer = bleeding
patients with Hepatic, renal disease or gall stones
how does nicotinic acid work ?
Antiilipolytic = reduce FA = reduce TAG synthesis
decrease LDL but greatly increase HDL
Name 3 ADRs of nicotinic acid (Niacin)
Flushing, headaches, itching (use aspirin to stop PGs)
hepatotoxicity , GI problems. poor tolerance due to hepatic metabolism creating metabolites
how does ezetimibe work ?
what about its metabolism and elimination ?
what dose should you give ?
Cholesterol absorption inhibitors, act at brush border of SI stopping NCPCP1L1 transporter = reduces absorption of cholesterol by 50%
prodrug converted to glucuronide which goes into enterohepatic circulation = site of action limiting exposure, secreted by bile
10mg no escalation
name 2 ADRs of Ezetimibe
headaches, adbo pain, diarrhoea but well tolerated
What multiple target therapy?
Combination of statin and ezetimibe
when should you add fibrates or nicotinic acid to statins ?
Familial hypercholesterolaemia
what is guide target for who have CVS event in terms of LDL and total cholesterol ?
2mmol/L
4mmol/L
How does monoclonal antibody thearpy reduce LDL?
Inhibits PCSK9 protein , reduces degradation of LDL-R so more can attach and enter cells via receptor mediated endocytosis
name 2 antibodies used for Hyperlipidemia
Alirocumab , Evolocumab
name 3 non POM options for hyperlipidemia
plante sterols , grains (similar to cholestrol so competes for absorption )
Fish oils, fibre , vit c/e, alcohol (HDL only increase TAG)
What 2 tools can be used to calculate CVS risk ?
Manchester table , QRISK
