Dyslipidaemias: diagnosis, pharmacotherapy and prevention Flashcards
(83 cards)
1
Q
What does cholesterol mean?
A
- cholos = bile - steros = solid - ol = alcohol
2
Q
What does atherosclerosis mean?
A
- atheros = greek work for glue - sclerosis = german for hardening
3
Q
What is the basic structure of a triglyceride?
A
- glycerol backbone - three fatty acids
4
Q
What is a lipoprotein?
A
- proteins that are soluble in water - able to carry lipids around the body
5
Q
What are the 3 main components of lipproteins?
A
1 - cholesterol 2 - triglycerides 3 - apoproteins
6
Q
What is the primary aspect of lipoproteins that determines the structure and function?
A
- apoproteins
7
Q
What is the main element of the core of lipoproteins?
A
- cholesterol esters - triglycerides
8
Q
What is the main element of the outer surface of lipoproteins?
A
- apoproteins - phospholipids - cholesterol free
9
Q
What is the major difference between free and esterified cholesterol?
A
- free = biologically active but cytotoxic - ester = safe/protected form for storage
10
Q
What are the 2 different lipoproteins that we need to be aware of that are commonly measured in the blood?
A
- low density lipoproteins (LDL) - high density lipoproteins (HDL)
11
Q
Why are low density lipoproteins (LDL) classed as the bad lipoproteins?
A
- they contain the majority of the bodies cholesterol - stored in body as fat
12
Q
Where is the majority of the cholesterol in the body prodcued?
A
- liver
13
Q
What is 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA)?
A
- intermediate precursor of cholesterol
14
Q
What is the rate limiting step and the target of statins in an attempt to reduce cholesterol synthesis?
A
- 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase - HMG-CoA converted to Mevalonate
15
Q
How are bile acids formed?
A
- synthesised in liver from cholesterol
16
Q
What is the function of bile acids?
A
- secreted into GIT by gall-bladder - act as emulsifiers for fat digestion
17
Q
What is the basic principle of exogenous lipid transport?
A
- lipids digested in GIT - processed into chylomicrons - absorbed into lymphatic system
18
Q
Once chylomicrons have been absorbed during exogenous lipid transport, how are triglycerides and fatty acids absorbed by capillaries?
A
- lipoprotein lipase released from capillaries - triglycerides released from chylomicrons
19
Q
Once chylomicrons have moved throughout the body, what happens to the remnants of them during exogenous lipid transport?
A
- remnants rich in cholesterol return to liver - cholesterol and bile are secreted into GIT
20
Q
What is the basic principle of endogenous lipid transport?
A
- liver processing of lipoproteins - lipoproteins delivered around the body
21
Q
In endogenous lipid transport what are the 2 main lipoproteins released from the liver?
A
- very low density lipoproteins (VLDL) - low density lipoproteins (LDL)
22
Q
In endogenous lipid transport very low density lipoproteins (VLDL) are created and released from the liver into the circulation. What is the first thing that happens to them in the capillaries?
A
- lipoprotein lipase is released from capillaries - TAG and fatty acids are released from VLDL and absorbed by capillaries
23
Q
In endogenous lipid transport once very low density lipoproteins (VLDL) have had most of their TAGs absorbed by capillaries, what do VLDL become?
A
- intermediate lipoproteins
24
Q
In endogenous lipid transport what happens to the intermediate lipoproteins that are formed from VLDL?
A
- enter the liver - processed into low density lipoproteins
25
In endogenous lipid transport what happens to low density lipoproteins (LDL)?
- LDLs are transported to peripheries - LDL receptors bind to LDL - cholesterol is stored in tissues
26
What is the reverse pathway involved in lipid transport?
- free cholesterol in tissues is absorbed by high density lipoproteins (HDL) - HDL transport cholesterol to liver for processing
27
What are the 3 pathways for lipid transport in the body?
1 - exogenous 2 - endogenous 3 - reverse
28
What is included in total cholesterol, and what is the healthy target?
- LDL and HDL - \<5mmol/L - LDL/HDL ratio \>3.5
29
What is the healthy target for LDL?
- \<3mmol/L
30
What is the healthy target for HDL?
- \>1.5mmol/L
31
What is the healthy target for triglycerides?
- 0.5 - 2mmol/L
32
What is primary dyslipidaemia?
- error in metabolism - generally caused by genetics
33
What are the 2 most common things affected by primary dyslipidaemia?
- abnormal lipoprotein structure - abnormal lipoprotein receptors
34
What is the Frederick classification?
- classification of dyslipidaemia
35
What is familial hypercholesterolaemia type IIa?
- very high LDL cholesterol
- \>5mmol/L even from birth
- \>7/5mmol/L for total cholesterol
36
What causes familial hypercholesterolaemia type IIa?
- autosomal (non sex chromosome specific) dominant genes
- 1 inherited = bad
- 2 inherited = really bad
37
What do the specific mutations in familial hypercholesterolaemia type IIa cause?
- mutations causing absence or very low LDL receptors
- cholesterol remains in blood
- increased risk of atherosclerosis
38
Is familial hypercholesterolaemia type IIa common?
- no - 0.5% of the population
39
What is familial combined hyperlipidaemia type IIb?
- moderatley high levels of LDL, VLDL and triglycerides
40
What causes familial combined hyperlipidaemia type IIb?
- autosomal (non sex chromosome specific) dominant genes
- 1 inherited = bad
- 2 inherited = really bad
- can be a number of genetic causes
41
How common is familial combined hyperlipidaemia type IIb?
- relatively common
- 10% of population
42
What are 2 very common clinical presentations, what may be useful in identifing a patient with familial combined hyperlipidaemia type IIb?
- insulin resistance
- obesity
43
In familial combined hyperlipidaemia type IIb what is the most common apolipoprotein affected?
- mutated apolipoprotein B-100 (ApoB-100)
- overproduction of ApoB-100
- common in LDL and VLDL
44
Familial combined hyperlipidaemia type IIb accounts for 20% of what premature what?
- premature ischemic heart disease
- premature = anyone \<70%
45
What is familial hypertriglyceridaemia type IV?
- elevated triglycerides
- \>5mmol/L
- cholesterol can be normal
46
What are 3 very common clinical presentations of patients with familial hypertriglyceridaemia type IV?
- insulin resistance
- obesity
- eruptive xanthomas
47
What is one of the most common finding in patients with familial hypertriglyceridaemia type IV that is difficult to understand why it happens?
- acute pancreatitis
- seen in patients with triglyceride levels \>10mmol/L
48
What causes familial hypertriglyceridaemia type IV and is it common?
- multiple genetic defects
- 1% of population
49
What is familial hyperchylomicronamia type I?
- increased chylomicrons
- deficiency in lipoprotein lipase of capillaries
- blood is creamy
- genetic defects
50
What is familial dysbetalipoproteinemia type III?
- decreased apoprotein E
- poor clearance of cholesterol by liver
- causes palmar xanthomas
- genetic defects
51
What is xanthelasmata?
- xanthos is greek for yellow
- elesma greek for plate/near eye
- fatty deposits around the eyes
- normally macrophages containing lipids
52
What is tendon xanthoma?
- fatty build up in tendons
53
What is palmar xanthoma?
- fatty build up on palms of hands
- common in familial dysbeta-lipoproteinemia
54
What is eruptive xanthoma?
- red/pink lumps - itchy and raised
- common in hypertriglyceridaemia
55
Are there any operations for hyperlipidaemia?
- no
56
What is the most common advice given to someone with hyperlipidaemia?
- lifestyle interventions
57
What is the first line of defence for a patient with hyperlipidaemia?
- statins
58
What is the mechanism of action for statins?
- inhibit HMG-Coa reductase in liver - HMG-CoA does not become mevalonate
59
What are the main effects on lipoproteins and triglycerides following statins?
- ⬇️ LDL, total cholesterol and TAG - ⬆️ HDL
60
What are the 2 most common statins prescribed?
- atorvastatin (MOST COMMON) - simvastatin
61
Statins have been shown to reduce all cause mortality, but what does that mean?
- reduced death from any cause
62
In addition to reducing cholesterol what can statins do to atherosclerosis plaque formation?
- reducing inflammation from cytokines - reduce cholesterols in necrotic core - both stabilise the atherosclerosis
63
What is the most common side effect from statins?
- myalgia (muscle pain)
64
In addition to myalgia, what other side effects can be seen with statin use?
- rhabdomyolysis (muscle breakdown) - arthralgia (joint pain) - liver dysfunction
65
What is the Framlington study?
- study of CVD risk in the town of Framlington, USA
66
What was the first risk score for cardiovascular disease?
- Framlington risk score
67
What are the 2 most common risk scores used in the UK?
- Q-Risk - JBS3
68
Which cardiovascular risk score do NICE recommend using?
- Q-risk
69
When do NICE recommend someone should be prescribed a statin?
- patient has a \>10% risk of developing CVD in next 10 years
70
When patients are prescribed statins, how often do NICE recommend patients blood biochemistry should be tested?
- every 3 months
71
What is the target for LDL reduction recommend by NICE for someone taking a statin?
- \>40% reduction in LDL
72
Are statins the only drug recommended by NICE based on estimated risk?
- yes
73
What are fibrates?
- drugs that aim to increased catabolism (b oxidation) - increased uptake of fats
74
Bezafibrate is the first line drug of choice for patients with hypertriglycaemia. What is the mechanism of action for this drug?
- increased activation of lipoprotein lipase - reduces TAG and LDL - increased HDL
75
What are the common side effects of Bezafibrate?
- myalgia - GIT disturbances (diarrhoea)
76
Cholestyramine acts in the GIT and is a bile salt sequestrants, what is the mechanism of action of this drug?
- reduces bile absorption - reduces cholesterol and LDL
77
What are the side effects of Cholestyramine, a bile salt sequestrants?
- reduces all fat absorption - reduces fat soluble vitamines (ADEK) - GIT disturbances (diarrhoea)
78
Ezetimbe is an alternative to Cholestyramine, what is the mechanism of action of Ezetimbe?
- inhibits cholesterol absorption only - commonly used alongside statins
79
What are the side effects of Ezetimbe?
- mild GIT disturbances (diarrhoea)
80
What are PCSK9 receptors?
- enzyme that binds to LDL receptors - maintains cholesterol homeostasis
81
Evolocumab is a PCSK9 inhibitor, what does this drug do?
- monoclonal antibody (mab at end of name) - inhibits PCSK9 enzyme - increased LDL receptors and decreased cholesterol in blood
82
Evolocumab is a PCSK9 inhibitor that has been shown to be effective at reducing LDL, TAG and and increased HDL, but it is expensive. Which patients would generally be prescribed this drug?
- hypercholesterolemia patients - patients non-response to statin
83
What are the common side effects of Evolocumab a PCSK9 inhibitor?
- cough - flu like symptoms
