Dyslipidemia - Sue's slides

Question 1

Differentiate primary and secondary hyperlipoproteinemia.

(online source)

Answer 1

Hyperlipoproteinemia can be a primary or secondary condition.

Primary hyperlipoproteinemia is often genetic. It’s a result of a defect or mutation in lipoproteins. These changes result in problems with accumulation of lipids in your body.

Secondary hyperlipoproteinemia is the result of other health conditions that lead to high levels of lipids in your body. These include:

diabetes
hypothyroidism
pancreatitis
use of certain drugs, such as contraceptives and steroids
certain lifestyle choices

Question 2

What are some symptoms of hyperlipoproteinemia? (elevated VLDL and triglycerides)

(online source)

Answer 2

Lipid deposits are the main symptom of hyperlipoproteinemia. The location of lipid deposits can help to determine the type. Some lipid deposits, called xanthomas, are yellow and crusty. They occur on your skin.

Many people with this condition experience no symptoms. They may become aware of it when they develop a heart condition.

Other signs and symptoms of hyperlipoproteinemia include:

pancreatitis
abdominal pain
enlarged liver or spleen
heart attack
stroke

Question 3

What is hypertriglyceridemia?

(some online sources)

Answer 3

Elevated blood triglycerides which can contribute to atherosclerosis, even without elevated total cholesterol.

Question 4

What is hypercholesterolemia?

(online source)

Answer 4

Defined as high levels of LDL in the blood.

Question 5

Management of dyslipidemia should always include____? Give examples

(big slide alert)

Answer 5

Management of dyslipidemia should always include dietary measures:

-Total fat, sucrose and especially fructose increase VLDL.

-ETOH can cause significant hypertriglyceridemia

• Limit calories from fat to 20-25% of daily intake, sat. fats to <7%, cholesterol to <200mg/day

-Dietary supplements (eg. omega 3) or consumption of specific foods (eg fresh salmon can significantly lower triglycerides

-More veggies

Also: increase cardiovascular exercise

Question 6

All dyslipidemia medications are contraindicated in pregnancy but are safe to use when breastfeeding.

True or false?

Answer 6

False, contraindicated in both pregnancy and breastfeeding.

Question 7

What are the 6 medication options/approaches to reducing lipid levels?

Answer 7

Statins

Fibrates

Niacin

Bile acid binding agents

Inhibitors of intestinal sterol absorption

Newer agents (not covered)

Question 8

Which drugs are competitive inhibitors of HMG-CoA reductase and what does this mean (what effect in the body)?

Answer 8

Statins.

By impairing the synthesis of isoprenoids, they induce an increase in high affinity LDL receptors which increases catabolism and extraction of LDL from the blood.

They say
Get the heLL-D-L outta here, STAT! (in)

Question 9

What time of day is it best to take a statin, and why?

Answer 9

IT is best to take it in the evening because cholesterol synthesis occurs primarily at night.
Absorption of statins is enhanced by food (except for pravastatin and pitavastatin).

Question 10

Statins should be used with caution and in reduced dosages in which populations?

Answer 10

Patients with hepatic parenchymal disease

Those or north Asian descent (due to genetic polymorphsm)

The elderly

Severe hepatic disease

Question 11

What is a risk associated with statin use?

How often should you monitor for this?

Answer 11

Elevated serum aminotransferase activity (up to 3x normal). Measure at baseline, a 1-2 months and then every 6-12 month if patient is stable.

As per text - d/c statin, levels will normalize to pre-drug level.

As per text, very rare risk of myopathy and rhabdo - can often experience muscle cramps but rarely leads to rhabdo. The CVS risks of dyslipidemia are greater that the risk of myopathy and rhabdo.

Question 12

What are 3 agents identified by Sue that affect statins and put a patient at risk for toxicity?

Answer 12

Macrolide antibiotics

Cyclosporine

Ketoconazole

(But then she adds “etc” so I don’t know if she will be asking for more in depth knowledge on the exam)

Question 13

______ have been shown useful in lowering VLDL and, in some patients, LDL as well.

Answer 13

Fibrates. (fibric acid derivatives)

Question 14

If a patient with dyslipidemia is not responding after making non-pharmacological changes and possibly using a statin, consider using a ______.

Answer 14

Fibrate.

Sue doesn’t specify adding a fibrate or changing out in place of a statin but I searched bit and see they are safe to use together and show benefit.

Question 15

How do fibrates work?

Answer 15

Fibrates function primarily as ligands (a molecule that binds to another) for the nuclear transcription receptor PPAR-alpha.

Fibrates increase lipolysis of lipoprotein triglyceride and increase oxidation of fatty acids in the liver and striated muscle.

Question 16

Fibrates are useful in treating hypertriglyceridemia in which ________ predominate.

Answer 16

VLDL

Question 17

How does niacin affect lipid levels?

Answer 17

Decreases triglyceride and LDL levels, and often increases HDL!

-inhibits VLDL secretion, in turn decreasing production of LDL.

-inhibits the intracellular lipase of adipose tissue via receptor-mediated signaling, possibly reducing VLDL production by reducing the the flux of free fatty acids to the liver.

Question 18

Combination therapy including niacin has been associated with regression of atherosclerotic coronary lesions.

True or false.

Answer 18

True

Question 19

In combination with a resin or reductase inhibitor, niacin normalizes LDL in most patients with ___________________.

Answer 19

Familial hypercholesterolemia (and other forms).

Question 20

There are multiple risks associated with niacin toxicity due to interactions with:

Answer 20

ASA, NSAIDS, antacids and antihypertensives.

Question 21

Is niacin a good choice for hypercholesterolemia, for people living with multiple comorbidities?

Answer 21

No because of the risk of niacin toxicity due to drug interactions with ASA, NSAIDS, antacids and antihypertensives.

Question 22

Are bile acid-binding resins commonly used in primary care?

Answer 22

No.

Question 23

When are bile acid-binding resins recommended?

Answer 23

For isolated increases in LDL (not used very often)

May be used pre-surgery

Question 24

What is a risk of using a resin if a patient has hypertriglyceridemia?

Answer 24

May increase VLDL levels.

Question 25

Where do bile acid-binding resins work in the body?

Answer 25

They bind bile acids in the intestinal lumen and prevent their reabsorption.

They are insoluble in water.

Question 26

Common side effects of bile acid-binding resins?

Answer 26

Constipation and bloating (often alleviated by adding dietary fibre)

Heartburn

Diarrhea

Question 27

Resins should be avoided in patients with ___?

Answer 27

Diverticulitis

Question 28

Malabsorption of Vitamin K and folic acid have been reported with the use of _____?

Answer 28

Bile acid-binding resins.

Question 29

Ezetimibe inhibits absorption of ______ and ______?

Answer 29

Phytosterols, cholesterol

Question 30

Added to statin therapy, ezetimibe provides additional effect by _____?

Answer 30

Decreasing LDL levels and further reducing dimensions of atherosclerotic plaques/

Question 31

Where is ezetimibe absorbed?

Peak blood levels reached in ______ hours?

Half life?

Answer 31

Readily absorbed and conjugated in the intestine to an active glucuronide.

Peak blood levels in 12-14 hours

Half life of 22 hours

Question 32

Ezetimibe is synergistic with ____________ ____________, providing additional decrements as great as 25% in LDL

Answer 32

Reductase inhibitors

Question 33

When combining dyslipidemia agents, how should you approach the dosing?

Answer 33

The lowest effective doses of each medication should be used.