Lipid lowering drugs Flashcards
What does hypercholesterolaemia lead to?
Atherosclerosis which leads to IHD, peripheral vascular disease, cerebrovascular disease
What are the risk factors for atherosclerosis?
Genetic Hypercholestrolaemia Hypertension Smoking Obesity Hyperglycaemia Reduced physical activity Infection (poor dental hygiene, increased CRP, low grade inflammation)
What drugs induce dyslipidaemia?
B-blockers Thiazides Corticosteroids Retinoids Oral contraceptives Anti HIV
What are lipoproteins?
Central core of hydrophobic lipid, encased in phospholipid, cholesterol and apolipoproteins
HDL, LDL, VLDL
What are chylomicrons?
Transport triglycerides and cholesterol from GI tract to liver
Free FA released and cholesterol is stored, oxidised to bile salts or released to VLDL, LDL, HDL
What does VLDL do?
Transports cholesterol and TGs to the tissues, where the TGs are removed
What does LDL do?
Large component of cholesterol, taken up by liver and tissues, via endocytosis via an LDL receptor
What does HDL do?
Absorbs cholesterol from cell breakdown and transfers it to VLDL + LDL
What is an ideal cholesterol?
<5.0mmol/l
What is atherogenesis?
Damage to the blood vessel Inflammatory response Cholesterol-rich deposits form Inflammatory mediators may lead to growth of VSM/connective tissue Plaques form
What is the lifestyle management for atherosclerosis?
Stop smoking Treat HT/DM Exercise Drug-induced? Low cholesterol diet (only 25-30% cholesterol comes from diet)
What is the pathway for cholesterol synthesis?
Hydroxymethylglutaryl TO mevalonate (synthesised by HMG-CoA reductase)
TO cholesterol
What are statins?
Simvastatin, pravastatin, atorvastatin, fluvastatin
Reduce plasma cholesterol
The reduction in hepatic cholesterol synthesis leads to an up regulation of hepatic LDL receptors, promoting LDL uptake
What are statins less effective in?
Homozygous familial hypercholesterolaemia, cannot make LDL receptor
Artorvastatin may be effective
Statins are effective in heterozygous disease
What does it mean that statins are hepatoselective?
Liver is the main site of cholesterol synthesis, extra hepatic sites synthesise essential cholesterol
1st pass metabolism: 5% reaches systemic circulation
What is hyperlipoproteinaemia?
IIa evevated LDL
IIb elevated LDL/VLDL
Statins are effective in both
What did the 4S trial show?
35% reduction in LDL (increased HDL)
Over 5 years, 30% reduction in mortality, 42% reduction in death from CAD
What can statins lead to the regression of?
Atherosclerosis
Lipid depletion leading to stabilisation of lesions
Improve endothelial function
Statins reduce progression of carotid disease and risk of stroke
What did the 2002 heart protection study show?
40mg simvastatin to high risk patients
25% reduced MI, stroke, revascularisation even in patients with low/norma`l cholesterol
What did the ASTEROID 2006 study show?
High dose rosuvastatin (40mg)
53% reduction in LDL
Regression of coronary atherosclerosis
What did the JUPITER 2008 study show?
Rosuvastatin (20mg) healthy patients with normal cholesterol but elevated CRP (CV risk)
Reduced cholesterol and CRP
Reduced risk of MI and stroke by 50%
Beneficial for normal population?
What do the 2014 NICE guidelines state about who should take statins?
> 10% risk of CVD
20mg atorvastatin (low intensity)
Secondary prevention/pts with CVD
80mg atorvastatin (high intensity)
When should cholesterol be taken?
At night
Offsets a nocturnal increase in cholesterol synthesis
NOT atorvastatin
What cautions should you take when prescribing statins?
Use with care in liver disease- monitor LFTs
May cause rhabdomyolysis- report muscle pains, increased by additional use of vibrates, pravastatin less likely to cause it
Simvastatin is now OTC
What drugs does simvastatin interact with?
Contraindicated with macrolides
Interacts with amlodipine, verapamil, dilitiazem
Which statin can you prescribe with amlodipine?
Pravastatin doesn’t react
Use 20mg simvastatin as maximum dose
Who are patients which are high risk for developing CVD?
Males 45-55 and females >55 Family history of IHD Smokers Overweight S Asians Indian
What are the implications of OTC statins?
Refer angina to GP Monitoring- hepatotoxicity Counsel re muscle pains Interactions- HIV protease inhibitors, ciclosporin, azoles, fibrates, anticoagulants, macrocodes Treatment won't be documented with GP
What are fibrates?
Bezafibrate, gemofibrozil
Activate PPAR-a alters lipoprotein metabolism
Promote breakdown in VLDL (small reductions in LDL and increase in HDL)
Reduce triglycerides- used with statins
Decrease glucose use in DM
Reduce IHD not mortality
Can cause rhabdomyolysis
What are cholesterol absorption inhibitors?
Ezetimbe
Prevents cholesterol absorption
For use on top of a statin
What do fish oils do?
Used for hypertriglyceridaemia
Increase LDL
Low incidence of coronary artery disease is eskimos (eicosapentaenoic and docosahexaenoic acid)
Fish diet after MI reduced mortality and reinfarction
Eicosapentaenoic acid competes with arachidonic acid for COX
What is sitostanol?
Functional food Present in benevolent margarine Prevents absorption of cholesterol Reduces LDL cholesterol by 10-15% Helpful add on to dietary restrictions and statin therapy
What is the stepped management for hypercholesterolaemia?
Statin +reduce risks
Add a fibrate
Add ezetimibe
What is the stepped management for hypertriglyceridaemia?
Lifestyle changes Fibrate or fish oil Statin and reduce risks Add a fibrate Add ezetimibe
