hyperlipidemias

Question 1

name 3 things that cholesterol makes / maintians

Answer 1

cell membrane integrity, steroid hormones, bile acids and Vit D

Question 2

Outline the pathogenesis of Atherosclerosis

Answer 2

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

Question 3

what is the role of HDL ?

Answer 3

transport excess cholesterol from cells to liver for recycling

Question 4

for every 1mmol/l of total cholesterol reduction =

Answer 4

20% decrease in risk CVD diease

Question 5

when can fatty streaks start to from?

Answer 5

20+ years onwards

Question 6

how do statins work ?

Answer 6

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

Question 7

Name 3 statins

Answer 7

Atorvastatin , simvastatin , Fluvastatin and Lovastatin

Question 8

Name 3 additional benefits of statins

Answer 8

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

Question 9

what is the half life of simvastatin and atrovastatin ?

Answer 9

Simvastatin - 2 hours, take at nigth

Atorvastatin - over 30 hours

Question 10

what are some ADRs of statins?

Answer 10

slight LFT increase
low-level myalgia with amiodarone
Rhabomyololysis
GI disruption , nausea and headaches

Question 11

what is NNT and what is the average NNT in statins?

Answer 11

NNT= Number needed to treat and is about 18 for statins which is quite low

Question 12

what is NICE guidelines of Statins?

Answer 12

Artorvastatin
20mg for people with 10% risk of CHD
80mg daily for people with heart disease

Question 13

why should you take simvastatin at night ?

Answer 13

low t1/2 , LDL receptor made at night due to circadian rhythm

Question 14

How do fibrates work ?

Answer 14

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

Question 15

Name 2 fibrates

Answer 15

Fenofibrate
ciprofribrate
gemfibrozil

Question 16

name 3 side effects of fibrates

when should you not use firbates ?

Answer 16

Upset GI, Gall stones, myositis, abnormal LFTs, warfarin inducer = bleeding
patients with Hepatic, renal disease or gall stones

Question 17

how does nicotinic acid work ?

Answer 17

Antiilipolytic = reduce FA = reduce TAG synthesis

decrease LDL but greatly increase HDL

Question 18

Name 3 ADRs of nicotinic acid (Niacin)

Answer 18

Flushing, headaches, itching (use aspirin to stop PGs)

hepatotoxicity , GI problems. poor tolerance due to hepatic metabolism creating metabolites

Question 19

how does ezetimibe work ?
what about its metabolism and elimination ?
what dose should you give ?

Answer 19

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

Question 20

name 2 ADRs of Ezetimibe

Answer 20

headaches, adbo pain, diarrhoea but well tolerated

Question 21

What multiple target therapy?

Answer 21

Combination of statin and ezetimibe

Question 22

when should you add fibrates or nicotinic acid to statins ?

Answer 22

Familial hypercholesterolaemia

Question 23

what is guide target for who have CVS event in terms of LDL and total cholesterol ?

Answer 23

2mmol/L

4mmol/L

Question 24

How does monoclonal antibody thearpy reduce LDL?

Answer 24

Inhibits PCSK9 protein , reduces degradation of LDL-R so more can attach and enter cells via receptor mediated endocytosis

Question 25

name 2 antibodies used for Hyperlipidemia

Answer 25

Alirocumab , Evolocumab

Question 26

name 3 non POM options for hyperlipidemia

Answer 26

plante sterols , grains (similar to cholestrol so competes for absorption )
Fish oils, fibre , vit c/e, alcohol (HDL only increase TAG)

Question 27

What 2 tools can be used to calculate CVS risk ?

Answer 27

Manchester table , QRISK