Hyperlipidemia

Question 1

Liver maintains a pool of cholesterol at all times. What are the routes of what happens to that cholesterol

Answer 1

1. broken down into bile acids to be secreted into intestine
2. packaged into VLDL to go into circulation

Question 2

Liver maintains a pool of cholesterol at all times. What are the various sources of this cholesterol

Answer 2

1. remnants of chylomicrons
2. from LDL taken up through LDL receptors on liver
3. make cholesterol from acetyl CoA using HMG-CoA

Question 3

Where does HDL come from? what it is function?

Answer 3

• extrahepatic takes up LDL and excretes HDL which is then ready to scavenge any free cholesterol found in the blood stream

Question 4

What is IDL?

Answer 4

• intermediate density lipoprotein
• formed from
  
  • HDL that has picked up cholesterol
  • VLDL after it has given free fatty acid to tissues

Question 5

what happens to intermediate density lipoprotein

Answer 5

They are cleared from the plasma into the liver by receptor-mediated endocytosis, or further degraded to form LDL particles.

Question 6

cause of familial hypercholesterolemia

Answer 6

LDL receptor deficiency -> leads to high LDL

Question 7

what happens to cholesterol levels during weight loss

Answer 7

• cholesterol levels are low during weight loss
  
  • check after weight loss has stabilized for one month

Question 8

in patients with hyperlipidemia, dietary changes should always be instituted first except in patients wtih

Answer 8

• coronary or peripheral vascular disease
• familial hypercholesteremia

Question 9

MOA of statins

Answer 9

• blocks de novo synthesis of cholesterol
• statins are the structural analog of HMG-CoA reductase
• reduced plasma LDL by inhibiting the reductase to increase high affinity LDL receptors

Question 10

DOC for decreasing LDL levels

Answer 10

statins

Question 11

which two of the statin drugs are inactive and hydrolyzed to active form

Answer 11

• Lovastatin
• Simvastatin

Question 12

why should patients take statins in the evening

Answer 12

• diurnal pattern of cholesterol synthesis; de novo cholesterol synthesis peaks at night

Question 13

What are the hallmark adverse effects of statins

Answer 13

• increase levels of serum aminotransferase (LFTs)
• Myopathy and muscle pain

Question 14

when are statins contraindicated

Answer 14

• pregnancy (category X)
• active hepatic disease

Question 15

metabolism of statins

Answer 15

liver by P450s

Question 16

P450 inhibitors have what effect on statins

Answer 16

• will increase the plasma concentrations of statins
• ex: grapefruit juice, macrolides, ketoconazole

Question 17

list the bile acid-binding resins

Answer 17

• Cholestyramine
• Colestipol
• Colesevelam

Question 18

MOA of bile acid-binding resins

Answer 18

• bind to bile acids and prevent their intestinal reabsorption
• decrease in bile acids -> increased expression of hepatic LDL receptors -> increased uptake of plasma LDL to make more bile acids
  
  • decreased LDL levels will decrease plasma cholesterol (20%)

Question 19

why does bile acid binding resins have no effect in homozygous familial hypercholesterolemia

Answer 19

there are no functional LDL receptors

Question 20

indications to use bile acid binding resins

Answer 20

• whenever LDL is elevated

Question 21

why is bile acid binding resins not effective in hypertiglyceridemia

Answer 21

may increase VLDL

Question 22

hallmark adverse effect of bile acid binding resins

Answer 22

constipation and bloating

• only stays in GI, not absorbed

Question 23

List the Niacins

Answer 23

• Nicotinic Acid
• Vitamin B3

Question 24

MOA of Niacin

Answer 24

• lowers VLDL and LDL by inhibiting VLDL secretion

Question 25

indications to use Niacin

Answer 25

* increases levels of HDL (most effective agent)

Question 26

hallmark adverse effects of Niacin

Answer 26

* cutaneous vasodilation -\> warm sensation, pruritus * impairs glucose tolerance

Question 27

List the Fibric acid derivatives (Fibrates)

Answer 27

* Gemfibrozil * Fenofibrate * Fenofibric acid

Question 28

MOA of Fibric acid derivatives (Fibrates)

Answer 28

* PPAR-a ligand (nuclear receptor) * upregulates LDL and other genes involved in fatty acid oxidation

Question 29

indications/theraputic use of Fibric acid derivatives (Fibrates)

Answer 29

* **decreased triglycerides** by lowering VLDL concentration * effective in **hypertriglyceridemia**

Question 30

hallmark adverse effect of Fibric acid derivatives (Fibrates)

Answer 30

* increased incidence of cholelithiasis or gallstones

Question 31

MOA of Ezetimibe

Answer 31

selectively blocks intestinal absorption of cholesterol and related phytosterols

Question 32

when is Ezetimibe used

Answer 32

* decreases LDL (18%) * combining Ezetimibe with a statin -\> synergism

Question 33

List the PCSK9 inhibitors

Answer 33

* Alirocumab * Evolocumab

Question 34

MOA of PCSK9 inhibitors

Answer 34

* normally, PCSK9 binds to LDLR and leads to LDL receptor degradation * Inhibiting the binding of PCSK9 to LDLR, the number of LDLRs available to clear LDL increases, thereby lowering LDL-C concentrations.

Question 35

how is PCSK9 inhibitors given

Answer 35

monthly, subcutaneous injections