Dyslipidemia

Question 1

What is cholesterol?

Answer 1

Cholesterol is a waxy substance produced and released in the liver

Question 2

What does cholesterol do in the body?

Answer 2

Cholesterol is used in the body to form cell membranes, aid in digestion, convert vitamin D in the skin, and develop hormones

Question 3

What is the difference between low-density lipids (LDL) and high-density lipids (HDL)?

Answer 3

ApoA protein on HDL is not on LDL ( it has ApoB instead)

LDL: contains cholesterol, low density of phospholipids and triglycerides, and delivers cholesterol to peripheral tissues. often end up in arterial plaques

HDL: Contains cholesterol, high density of phospholipids and triglycerides , removes excess cholesterol from tissues to liver for storage and excretion back into the bile. does not cause circulatory problems

Question 4

What are the main inherited lipoprotein disorders?

Answer 4

familial hypercholesteremia , familial combined hyperlipidaemia, hypertriglyceridaemia

Question 5

What is the function in LDL and hdl?

Answer 5

hdl -remove cholesterol from the blood
LDL - deliver cholesterol to both peripheral and liver cells.

Question 6

What disease is low HDL linked to?

Answer 6

Coronary artery disease

Question 7

What happens if a patient has low levels of HDL?

Answer 7

There will be less HDLs to remove the cholesterol in the blood which will increase the risk of coronary artery disease

Question 8

How can we increase HDL levels?

Answer 8

Exercise, low alcohol, no smoking, lowering triglycerides

Question 9

What are statins?

Answer 9

HMG-CoA reductase inhibitors

Question 10

What do statins do to reduce cholesterol?

Answer 10

The liver synthesizes cholesterol with the enzyme HMG CoA reductase. Statins block the HMG CoA reductase enzyme so there is less intracellular pools of cholesterol in the liver. This triggers an increase in LDL receptor number and activity. LDLs bind to these receptors which pick up cholesterol circulating in the bloodstream and transport them back into the cell/liver. Once inside the cell, the LDL is broken down to release cholesterol. The cholesterol is then used by the cell, stored, or removed from the body.

Question 11

Why is pravastatin a good drug choice for cholesterol?

Answer 11

Low side effect profile

Question 12

What drug is most effective at lowering cholesterol in the body?

Answer 12

Atorvastatin

Question 13

What are the common side effects of statins?

Answer 13

Upset stomach, Nausea, Constipation, Abdominal pain

Question 14

What are some of the interactions of statins?

Answer 14

antifungals, grapefruit juice inhibits CYP3A4 (lova-, simva-, less w/atorva)

Question 15

What patients do we give a statin to?

Answer 15

Patients with an established vascular disease of any type
High LDL
QRISK score greater than 10%
Diabetic
Congestive Heart disease
Atherosclerosis (Atherosclerosis is where your arteries become narrowed, making it difficult for blood to flow through them)

Question 16

What does Ezetimibe do to cholesterol in the body?

Answer 16

Targets the absorption of the cholesterol in the GI tract

Ezetimibe blocks Niemann-Pick C1 like 1 (NCPC1L1) (a Transporter mechanism of cholesterol into hepatocytes). by blocking the transport of cholesterol into chylomicrons reduces the cholesterol absorption at the liver. Therefore less LDL levels produced.

Ezetimibe significantly suppresses cholesterol absorption from the small intestine via the Niemann-Pick C1-like 1 (NPC1L1) pathway, possibly by a transporter-facilitated mechanism. This effect of ezetimibe significantly diminishes the cholesterol content of the liver, which in turn remarkably decreases bioavailability of cholesterol for hepatic secretion into bile.

Question 17

Who cannot use Ezetimibe?

Answer 17

Those with renal and liver impairment

Also, careful with patients on cyclosporine and any immunosuppressive drug that alters renal function

Question 18

What drugs interact with Ezetimibe?

Answer 18

Gemfibrozil and fenofibrate increase levels of ezetimibe

Question 19

What drugs have a positive effect on HDL?

Answer 19

Verapamil (calcium channel blocker), Doxazosin; antihypertensive increases HDL

Question 20

What group of people should you give a 20mg atorvastatin to?

Answer 20

People with a Qrisk over 10%
People with TYPE 1 DIABETES
- are older than 40 or
- had diabetes for more than 10 years
- had cardiovascular disease factors
- nephropathy
People with type 2 diabetes
People with chronic kidney disease

Question 21

What group of people should you give an 80mg atorvastatin to? And why is it beneficial?

Answer 21

in people who have already had a CVD event, such as a heart attack or stroke. High intensity statins are the most clinically effective option for the secondary prevention of CVD – that is, reducing the risk of future CVD events

Question 22

How are dyslipidaemia, atherosclerosis and diabetes related?

Answer 22

look at pic on phone

Question 23

What is the function of the adipose tissue and what concern can this cause to patients with diabetes and hyperlipidaemia?

Answer 23

Adipose tissue is where we find free fatty acids production. The fats cells in adipose produce endocrine hormones. In patients with increased fat proliferating cells such as with diabetes, the increased fat cells produce increased hormone levels of TNF alpha, resistin, leptins and INT-6 which are all linked to atherosclerosis.

Question 24

Why do patients with diabetes have increased levels of trigylcerides?

Answer 24

because of the increased production of VLDL, Apo B and LDL, and decreased levels of HDL and Apo A. Is due primarily to the increased generation of VLDL and because of the increased free fatty acids in the liver.

Question 25

What are the second line treatment for hyperlididaemia?

Answer 25

Evolocumab or Alirocumab

Question 26

What is the mechanism for PCSK9?

Answer 26

PCSK9 plays an important role in LDL metabolism

A serine protease expressed by live and intestine which promotes the degradation of LDL receptor:

Prevents the LDL receptor being recycled to the cell surface

Reduces the LDL receptor population on the cell surface

Reduces clearance of LDL receptor from circulation

Binding of LDL with PCSK9 leads to degradation of the LDL receptor, and then less LDL is removed from the circulation. Inhibiting PCSK9 from being degraded therefore promotes removal of LDL cholesterol from circulation