Lipid Lowering Drugs part1

Question 1

What risk does high lipid level which can cause plaque in arteries put patients at risk for

Answer 1

Coronary heart disease-blockage of heart that gives oxygen and nutrients

Ischemic cerebrovascular disease-stroke

Peripheral vascular disease- which may start in leg; occluded blood flow pain because of ischemia

Question 2

Why can cause people to have high lipid levels

Answer 2

It’s mostly due to diet getting too much food with cholesterol which is a lipid and saturated fats
Genetics

Question 3

Name the five classes of lipoproteins

Answer 3

There are not five only four
Chylomicrons
Very low density lipoproteins
Low density lipoproteins 
High density lipoproteins

Question 4

What is the source and function of chylomicrons

Answer 4

Chylomicrons are formed in the intestine and they transport triglycerides

Question 5

What is the source and function of very low density lipoproteins

Answer 5

The source of vldl is the liver and it transports endogenously formed triglycerides

Question 6

What is the source of low density lipoproteins and what is their function

Answer 6

Formed by break down of IDL while in circulation; delivers cholesterol to peripheral tissues

Question 7

what is the source and function of high density liproproteins

Answer 7

they are formed in the liver and remove used cholesterol from the tissues and brings it back to the liver; also will donate its apolipoproteins to chylomicrons and very low density liproproteins

Question 8

Which class of liproproteins can apoliprotein B-100 be found on

Answer 8

LDL and VLDL

Question 9

Where can apolipoprotein C(I,II,III) be found on

Answer 9

its found on CM, VLDL, and HDL

Question 10

What is a unique apolipoprotein on chylomicrons

Answer 10

B48

Question 11

Explain how cholesterol is absorbed from the intestine

Answer 11

1. food is digested (cholesteryl ester or cholesterol)
2. the cholesterol and cholesteryl ester is broken down to free fatty acid and free cholesterol
3. the free fatty acid goes straight into the intestinal cells, cholesterol being slightly charged need to be emulsified by bile acid from gallbladeder
4. the cholesterol and bile acid form micelles which can now enter into the intestinal cell
5. in the intestinal cell the cholesterol and free fatty acid join again to form chylomicrons
6. the chylomicrons travel through the lymphatic channels into the blood
7. from the blood into the liver
8. in the liver chylomicrons are used to make bile acids and VLDL.

Question 12

What are the four ways to intervene and control cholesterol

Answer 12

1. lower cholesterol intake thru the diet-lower animal fat
2. decrease cholesterol reabsorption in the intestine (small intestine) by using drugs like Ezetimibe
3. decrease bile acid reabsorption by using bile acid sequestrants
4. increase fiber: lower cholesterol absorption

Question 13

What are bile salts and where are they stored

Answer 13

A1: amphipathic molecules that work as detergents to help break up dietary lipids
A2: they are stored in the gall bladder, w/ cholesterol and phospholipids

Question 14

How is fibre used to lower cholesterol

Answer 14

fibre can bind to bile salts and cholesterol and stop reabsorption

Question 15

How are sitostanol ester lower cholesterol

Answer 15

its from plants, similar in structure to cholesterol and stops cholesterol from entering micellar phase and reduces its adsorption into the blood stream

Question 16

What is enterohepatic circulation

Answer 16

reabsorption of bile salts and cholesterol are transported back to the liver bound to albumin and recycled

Question 17

What is an example of sitostaol ester

Answer 17

Benecol margarine

Question 18

What are bile acid sequestrants

Answer 18

group of medications used for binding bile in the gastrointestinal tract–the bound cholesterol will then be lost in the stool

Question 19

What are bile acids used to treat

Answer 19

hypercholesterolemia and in some cases chronic diarrhea because when large amounts of bile acids enter the large intestine, they stimulate water secretion and intestinal motility in the colon which can cause diarrhea

Question 20

Explain the mechanism of bile acid resins over all how does it effect the body

Answer 20

1. bile acids will no be adsorbed again after resins are administered
2. liver can deal with this in two ways make more cholesterol or increase receptors for LDL to get cholesterol from blood (liver receptors). The receptors recognize apolipoprotein B100 and capture LDL-cholesterol
3. liver enzymes such as cholesterol 7 alpha-hydroxylase increases to form bile acids
4. these bile acids will be transferred as usual to the gallbladder
5. Overall, decrease in LDL-cholesterol
6. Note: there will be an increase in VLDL-triglycerides

Question 21

What is colestipol

Answer 21

Colestipol is one type of bile acid sequestrant its huge and just sits in the GI tract it binds bile acid and is lost in the stool

Question 22

How do bile acid resins work

Answer 22

most are anion exchange resins; they are high positively charged and bind to the negative bile acids. In all they lower the bodies pool of bile acids. As stated on other quiz cards, they lower bile acids which causes the body to compensate and increase liver LDL-receptors, increasing clearance or removal of LDL and lowers its levels in the blood

Question 23

When bile acid production increases, what also increases

Answer 23

an increase in production of VLDL

Question 24

What do bile acid sequestrants affect the adsorption of

Answer 24

many types of drugs; lowers blood levels and therapy effectiveness. Also fat soluble vitamins because bile acids are not there to emulsify them

Question 25

Name the three types of bile acid resins

Answer 25

1. Cholestyramine (Questran) 2. Colestipol (Colestid) 3. Colesevelam (Welchol)

Question 26

How many grams of cholestyramine should be take every day

Answer 26

4-6 grams/day

Question 27

How many grams of Colestipol should be take per day

Answer 27

5-20 grams/dday

Question 28

How many tablets of Colesevelam should be taken per day

Answer 28

6-7 tablets per day

Question 29

How many grams are in each Colesevelam tablet

Answer 29

0.625 grams or 625 mg

Question 30

How has the use of bile acid resin changed

Answer 30

there use has decreased mostly because of the effectiveness of statins; they are sometimes used as an adjunct to statins.

Question 31

What is the benefit of bile acid sequestrants

Answer 31

lower coronary events and lack systemic toxicity

Question 32

What is an important side effect of bile acid sequestrants

Answer 32

GI intolerance leading to constipation, bloating, abdominal pain, flatulence(gas), irritation of hemorrhoids, and an increase of liver enzymes because more bile acid needs to be made

Question 33

What are drug interactions

Answer 33

Drugs interactions are mainly caused by colestipol and cholestyramine but because the resins are positive they bind to most negatively charged drugs and stop absorption of drugs and fat-soluble vitamins

Question 34

How can we work around drug interactions with bile acid

Answer 34

We can give other drugs 1 hour before of 4-6 hours after giving the resin

Question 35

What are the uses of bile acid sequestrants. | Hint its 8 things

Answer 35

1. primary hypercholesterolemia 2. pruritus-a sensation that causes a desire or reflex to scratch- get it from bile acid excess that is deposited into the skin, maybe due to block of bile duct (colistasis) 3. diarrhea with excess fecal bile acids 4. tropical diarrhea 5. binding toxic agents, overdose of drugs, decrease adsorption of GI tract 6. Pseudomembraneous colitis- major infection- broad spectrum antibiotics helps with symptoms 7. lowers oxaluria- which is excessive calcium in the urine

Question 36

Although this supplement is not fat soluble, how do bile acid resin impact it

Answer 36

folic acid is not fat soluble but the resin decrease its absorption so it need to be supplemented during drug therapy

Question 37

Name the six toxic drugs that bile acid resins can decrease adsorption of

Answer 37

1. phenobarbital 2. warfarin 3. Lindane 4. lorazepam 5. Methotrexate 6. chlordecone 7. digitoxin

Question 38

What beneficial drugs are inhibited because of bile acid sequestrants- bind to

Answer 38

1. thiazides (a few) 2. furosemide 3. propranolol 4. L-thyroxine (levo-thyroxine) 5. cardiac glycosides 6. Coumarin anticoagulants 7. statins

Question 39

How is colestyramine packaged

Answer 39

its in individual packets or in bulk- the scoop measures out 4 grams/dose

Question 40

What is a trick you can use to decrease indigestion with colestyramine

Answer 40

leave the water and powder suspended over night

Question 41

How is colestipol packaged

Answer 41

its in bulk or individual packets of 5 gramss or a tablet as 1 gram

Question 42

Colesevelam is packaged how

Answer 42

it only in tablet form (0.625 grams)

Question 43

On page 5, what does the graph Effect of colesevalam on LDL-C display

Answer 43

It shows a study to observe the effects of colesevelam on LDL cholesterol, patients started with a baseline LDL-cholesterol of 130-220 mg/dL high and triglycerides of less than 300mg/dL (because it increase VLDL although less than the other two drugs) After 24 weeks LDL-c was lowered by 15% in patients taking 3.8g/day and 4.5 g/day lowered by 18%. The max effect was about 30%-statin are better at 60%. So overall colesevelam is less potent but you do avoid muscle pain

Question 44

Explain how the various lipoproteins are made in the body. See diagram on page 6

Answer 44

1. VLDL is made in liver and broken down by lipoprotein lipase while circulating----> the triglycerides go to tissues 2. remnant is turned into IDL---> 50% goes to liver and the other half is broken down again by lipoprotein lipase to LDL 3. LDL: 75% goes to liver 24% to extrahepatic tissues (other tissues that need cholesterol) 1% to blood vessels but really don't want cholesterol into blood vessels---HDL can reverse this, but in a pathological situation it will be greater than 1%

Question 45

Explain how cholesterol is endogenously synthesized

Answer 45

its made in the body 1. acetyl CoA and acetoacetyl CoA combine to form 3-hydroxy-3 methyl glytaryl-CoA (HMG-CoA) 2. HMG-CoA reductase enzyme will reduce this to mevalonic acid and continue to cholesterol 3. Therefore statins will inhibit this step

Question 46

What is the order of statins that will decrease the dose equivalence by decrease 25-30% in LDL

Answer 46

``` Peter Rose and Sam Love Pringles with flavor Pitavistatin Rosuvastin Atorvastatin Simvastatin Lovastatin Pravastatin Fluvastatin ```

Question 47

What are the doses that will lower by 25-35% of LDL

Answer 47

2,5,10,20,40,40, 80mg

Question 48

How to statins impact the body

Answer 48

to make up for the cholesterol that is not being made endogenously, increase LDL receptors pull cholesterol from the blood, overall both bile acid sequestrants both increase LDL receptors

Question 49

Explain how LDL receptors work in the body

Answer 49

1. the receptors will be exocytosed one the Apo B-100 bind to receptor on liver 2. cholesterol inside the LDL will be used and the receptor recycled