Lipid lowering drugs

Question 1

What does hypercholesterolaemia lead to?

Answer 1

Atherosclerosis which leads to IHD, peripheral vascular disease, cerebrovascular disease

Question 2

What are the risk factors for atherosclerosis?

Answer 2

Genetic 
Hypercholestrolaemia 
Hypertension
Smoking 
Obesity
Hyperglycaemia 
Reduced physical activity 
Infection (poor dental hygiene, increased CRP, low grade inflammation)

Question 3

What drugs induce dyslipidaemia?

Answer 3

B-blockers
Thiazides
Corticosteroids
Retinoids
Oral contraceptives
Anti HIV

Question 4

What are lipoproteins?

Answer 4

Central core of hydrophobic lipid, encased in phospholipid, cholesterol and apolipoproteins
HDL, LDL, VLDL

Question 5

What are chylomicrons?

Answer 5

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

Question 6

What does VLDL do?

Answer 6

Transports cholesterol and TGs to the tissues, where the TGs are removed

Question 7

What does LDL do?

Answer 7

Large component of cholesterol, taken up by liver and tissues, via endocytosis via an LDL receptor

Question 8

What does HDL do?

Answer 8

Absorbs cholesterol from cell breakdown and transfers it to VLDL + LDL

Question 9

What is an ideal cholesterol?

Answer 9

<5.0mmol/l

Question 10

What is atherogenesis?

Answer 10

Damage to the blood vessel 
Inflammatory response
Cholesterol-rich deposits form
Inflammatory mediators may lead to growth of VSM/connective tissue 
Plaques form

Question 11

What is the lifestyle management for atherosclerosis?

Answer 11

Stop smoking
Treat HT/DM
Exercise
Drug-induced?
Low cholesterol diet (only 25-30% cholesterol comes from diet)

Question 12

What is the pathway for cholesterol synthesis?

Answer 12

Hydroxymethylglutaryl TO mevalonate (synthesised by HMG-CoA reductase)
TO cholesterol

Question 13

What are statins?

Answer 13

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

Question 14

What are statins less effective in?

Answer 14

Homozygous familial hypercholesterolaemia, cannot make LDL receptor
Artorvastatin may be effective
Statins are effective in heterozygous disease

Question 15

What does it mean that statins are hepatoselective?

Answer 15

Liver is the main site of cholesterol synthesis, extra hepatic sites synthesise essential cholesterol
1st pass metabolism: 5% reaches systemic circulation

Question 16

What is hyperlipoproteinaemia?

Answer 16

IIa evevated LDL
IIb elevated LDL/VLDL
Statins are effective in both

Question 17

What did the 4S trial show?

Answer 17

35% reduction in LDL (increased HDL)

Over 5 years, 30% reduction in mortality, 42% reduction in death from CAD

Question 18

What can statins lead to the regression of?

Answer 18

Atherosclerosis
Lipid depletion leading to stabilisation of lesions
Improve endothelial function
Statins reduce progression of carotid disease and risk of stroke

Question 19

What did the 2002 heart protection study show?

Answer 19

40mg simvastatin to high risk patients

25% reduced MI, stroke, revascularisation even in patients with low/norma`l cholesterol

Question 20

What did the ASTEROID 2006 study show?

Answer 20

High dose rosuvastatin (40mg)
53% reduction in LDL
Regression of coronary atherosclerosis

Question 21

What did the JUPITER 2008 study show?

Answer 21

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?

Question 22

What do the 2014 NICE guidelines state about who should take statins?

Answer 22

> 10% risk of CVD
20mg atorvastatin (low intensity)
Secondary prevention/pts with CVD
80mg atorvastatin (high intensity)

Question 23

When should cholesterol be taken?

Answer 23

At night
Offsets a nocturnal increase in cholesterol synthesis
NOT atorvastatin

Question 24

What cautions should you take when prescribing statins?

Answer 24

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

Question 25

What drugs does simvastatin interact with?

Answer 25

Contraindicated with macrolides

Interacts with amlodipine, verapamil, dilitiazem

Question 26

Which statin can you prescribe with amlodipine?

Answer 26

Pravastatin doesn’t react

Use 20mg simvastatin as maximum dose

Question 27

Who are patients which are high risk for developing CVD?

Answer 27

Males 45-55 and females >55
Family history of IHD
Smokers
Overweight
S Asians Indian

Question 28

What are the implications of OTC statins?

Answer 28

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

Question 29

What are fibrates?

Answer 29

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

Question 30

What are cholesterol absorption inhibitors?

Answer 30

Ezetimbe
Prevents cholesterol absorption
For use on top of a statin

Question 31

What do fish oils do?

Answer 31

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

Question 32

What is sitostanol?

Answer 32

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

Question 33

What is the stepped management for hypercholesterolaemia?

Answer 33

Statin +reduce risks
Add a fibrate
Add ezetimibe

Question 34

What is the stepped management for hypertriglyceridaemia?

Answer 34

Lifestyle changes 
Fibrate or fish oil
Statin and reduce risks
Add a fibrate
Add ezetimibe