Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

IMED3001 > lipid lowering therapies > Flashcards

lipid lowering therapies Flashcards

1
Q

What do lipoproteins do?

A

They carry fats around the bloodstream

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What percentage of cholesterol is carried by LDL?

A

70%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is Lp(a) concentration determined by and why is it important?

A

It is very atherogenic and it is purely determined by genetics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the good bad and ugly lipoproteins (not technical terminology by any means but helps understand better)?

A

Good: HDL

Bad: VLDL, IDL, LDL, Lp(a)

Ugly: IDL, chylomicron remnant, Lp(a)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is characteristic of the exogenous lipoprotein transport pathway?

A

Chylomicrons which interact with lipoprotein lipase (LPL) forming a chylomicron remnant which interacts with a receptor (apo(e)) on the liver. Chymomycron remnant has a higher percentage of cholesterol compared to triglycerides. Chylomicrons have lots of triglycerides.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Which body parts have Lipoprotein Lipase?

A

Muscles and adipose tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the endogenous lipoprotein pathway?

A

VLDL interacts with LPL to form IDL which can bind to remnant receptor. Hepatic lipase breaks IDL down into LDL which interacts with LDL receptor to release the cholesterol and triglycerides.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What receptor do VLDL, IDL, and LDL use in the endogenous pathway?

A

Apo(B100)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How can cholesterol be lowered?

A

Lower saturated fats

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How can triglycerides be lowered?

A

Low energy and weight loss

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How do statins work?

A

Sterol Regulatory Element Binding Protein (SREBP) increases the amount of production of LDL receptors and acts to decrease the liver’s ability to synthesize cholesterol.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Where do lipophilic statins tend to go more often?

A

To the brain and muscles more than hydrophilic statins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What P450 can we find on Atorvastatin?

A

3A4 (important to know)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What P450 receptor is present on Rosuvastatin?

A

2C9 (limited)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What do statins do?

A

They can effectively reduce LDL-cholesterol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How do LDL -C levels correlate with CHD events?

A

Lower LDL levels are associated with lower percentage of CHD events.

1mmol/L reduction in LDL-c = 22% reduction in CVD risk irrespective of starting LDL-c concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the hepatic side effects of statins?

A

Mild increase in transaminase (0.5 - 3%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the cognitive side effects of statins?

A

Memory lass (rare)

Others suggest may prevent dementia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What do statins do to diabetes risk?

A

9% increase and linked to HMG CoA reductase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are statin side effects on muscle injury?

A

Myositis (rare <5/1000)

Dose dependent

Hydrophilic statins don’t enter muscles much

P450 interactions are important for this

Pre-existing conditions such as neuromuscular and endocrine conditions

Ethnicity (chinese people interact negatively with fibrates)

No increase with exercise but CK is higher

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How does ezitimibe reduce cholesterol?

A

By decreasing the reuptake of bile (bile is high in cholesterol)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Where is ezetimibeglucuronidated?

A

In the intestine by UGT1A1, 1A3, 2B7

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the side effects of ezetimibe?

A

Fatigue in ~2%

GI diarrhea in 2 - 4%

Increase transaminases in ~1%

Arthralgia in 3%

URTI symptoms in 3%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How many doses of ezetimibe are needed daily?

A

Due to 22 hour half life it only needs to be taken once daily

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How potent is ezetimibe at reducing cholesterol?

A

Not very, but when combined with statins it can have a huge effect.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

How does ezetimibe affect triglycerides and HDL?

A

Minimal changes to TG and minimal increase to HDL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What was the CVD outcome of ezetimibe?

A

It improved the condition.

It is great for sparing statins in those with muscle symptoms

28
Q

What do PCSK9 receptors do?

A

Receptor present in liver and kidneys associated with hypercholesterolaemia. Loss of function mutations were associated with reduction in CVD risk (28.8% reduction in risk)

29
Q

What is PCSK9 gene expression regulated by?

A

SREBP2 in response to cholesterol levels

30
Q

What did monoclonal antibodies against PCSK9 do in phase 1 trials?

A

Reduced LDL-c by 50 - 70%

Active in addition to statins (compound effect)

No heterogeneity in studies

Reduce Lp(a) (25%)

Reduce TG (10-30%)

Increase HDL (10%)

31
Q

What is the function of PCSK9?

A

Recycling of LDL-Receptors. If PCSK9 loses function then receptors don’t get recycled resulting in less LDL binding and breakdown

32
Q

What are the side effects of PCSK9 inhibitors?

A

Nasopharyngitis

Injection site reactions 5%

GI 1 - 6%

Hypertension 3%

Neurocongnitive 1%

33
Q

What is the problem with using PCSK9 inhibitors?

A

They have to be injected every 2 - 4 weeks and taken in addition to statins

34
Q

What is evolocumab?

A

TGA approved cholesterol lowering drug.

New drug used to treat familial hypercholesterolaemia or clinical ASCVD (atherosclerotic cardiovascular disease)

35
Q

What are the TGA and PBS approved drugs to use for cholesterol?

A

Alirocumab

Evolocumab

36
Q

What did fourier test result in?

A

21-27% reduction in CVD events but did not reduce CV mortality or all cause mortality

37
Q

What were the problems with using an ApoB antisense?

A

Increased hepatic fat

90% injections site reactions

and 50% influenza symtoms

38
Q

What does ApoB do?

A

Stop production of ApoB which prevents export of lipoproteins from the liver

39
Q

What were the side effects of MTP inhibitor?

A

Increase in hepatic fat and transaminase levels due to decrease in formation and release of lipoproteins from the liver

40
Q

What are the secondary causes of hypercholesterolaemia?

A

Lifestyle

41
Q

What are the secondary causes of hypercholesterolaemia?

A

Lifestyle (Weight loss, alcohol, controlling diabetes)

42
Q

What are fibrates?

A

PPARalpha activators

They increase FFA beta oxidation

They down-regulate ApoCIII

Increase catabolism (B48 in chylomicrons and B100 in VLDL)

43
Q

What is the efficacy of fibrates like?

A

increased HDL by 5 - 20%

Reduced TG by 5 - 20%

If there is severe TG then it increases LDL severely

44
Q

What was the overall result of using fibrates?

A

Meta analyisis of 45000 people showed no CVD benefit and trend to nonCVD harm RR=1.10ns

45
Q

What are remnant lipoproteins

A

Total cholesteral - HDL - LDL. if that’s greater than 1.5mmol/L then same risk as someone with LDL greater than 5mmol/L

46
Q

Who benefits most from fibrates?

A

people with dyslipidaemia (abnormal amounts of fat in blood)

47
Q

What are n3 Polyunsaturated FAs?

A

They reduce fatty acid synthesis and are complex and multifactorial.

48
Q

What are some examples of n3 Polyunsaturated FAs?

A

EPA and DHA

49
Q

What do n3 Polyunsaturated FAs do?

A

They reduce triglycerides

VLDL and non-HDL cholesterol while increasing LDL-c

50
Q

What is the benefit of consuming more polyunsaturated FAs?

A

Consuming marine based PUFAs reduces CVD

Lower triglycerides with a dose response. 9 - 26% change

51
Q

What does Niacin do?

A

Reduces TG synthesis via decreased hepatic DGAT (diacylglycerol acyltransferase-2)

Also reduces FFA flux from adipose tissue and enhances TRL clearnance

52
Q

How effective is Niacin?

A

Lowers TG 5 - 40%

Lowers LDL-c and Lp(a)

Increases HDL

However, no improvement was seen in cardiovascular disease outcome.

53
Q

What are the side effects of Niacin?

A

flushing

Itch

GI

Hyperglycaemia

54
Q

What is GLP1?

A

Glucagon like peptide 1

Secreted in response to a meal. Increases insulin, decreases glucagon, slows gastric emptying, and reduces caloric intake

55
Q

What are the side effects of GLP1?

A

GI cramps, nausea, vomiting, and weight loss.

56
Q

How effective was GLP1 at reducing TGs?

A

Reduced postprandial TGs on diabetics and IGT

Unknown effects on CVD it’s undergoing trials as we speak

Reduces HbA1c

57
Q

What does DPP-4 do?

A

Prolong activity of GLP1

increasing insulin production

decreasing glucagon

slowing gastric emptying

reducing calorie intake

58
Q

How often are DPP-4 inhibitors taken?

A

once a day orally

59
Q

What are the side effects?

A

Hypoglycaemia if combined with GLP1

Headaches

Nasopharyngitis

Nausea

Vomiting

Weight loss

Heart failure

60
Q

How effective are DPP-4 inhibitors?

A

They reduce TGs effectively by ~15%

May reduce LDL-c slightly

Reduce post prandial triglycerides

Not trialed yet so unkown how effective they are on CVD

Reduces HbA1c by 0.5 - 1%

61
Q

What are the DPP-4 inhibitors called pharmacologically?

A

gliptins

62
Q

What are thiazolidinediones?

A

PPARgamma agonists

They act on adipose tissue, muscle and liver increasing glucose uptake and decreasing glucose production

63
Q

What are side effects of thiazolidinediones?

A

weight gain

Oedema

Long bone fractures

Bladder cancer

64
Q

What is the most fundamental way to lipid therapy?

A

Mediterranean diet

Exercise

and smoking cessation

65
Q

How can LDL-c be lowered?

A

Statins are first line therapy (More = better but SEs are problematic)

Ezetimibe is the second line (some CVD outcome benefit and is a statin sparing agent)

PCSK9 inhibition through monoclonal antibody therapy is important to reducing cholesterol

Triglyceride reduction should be done after CVD risk is improved with statins and other stuff.

Lifestyle should be fixed with alcohol reduction

Fish oil due to the EPA and DPA content

Fibrates reduce CVD morbidity in diabetic dyslipidaemia by 25%

Diabetes control

IMED3001 (46 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions