Lipid Lowering Drugs part1 Flashcards
What risk does high lipid level which can cause plaque in arteries put patients at risk for
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
Why can cause people to have high lipid levels
It’s mostly due to diet getting too much food with cholesterol which is a lipid and saturated fats
Genetics
Name the five classes of lipoproteins
There are not five only four Chylomicrons Very low density lipoproteins Low density lipoproteins High density lipoproteins
What is the source and function of chylomicrons
Chylomicrons are formed in the intestine and they transport triglycerides
What is the source and function of very low density lipoproteins
The source of vldl is the liver and it transports endogenously formed triglycerides
What is the source of low density lipoproteins and what is their function
Formed by break down of IDL while in circulation; delivers cholesterol to peripheral tissues
what is the source and function of high density liproproteins
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
Which class of liproproteins can apoliprotein B-100 be found on
LDL and VLDL
Where can apolipoprotein C(I,II,III) be found on
its found on CM, VLDL, and HDL
What is a unique apolipoprotein on chylomicrons
B48
Explain how cholesterol is absorbed from the intestine
- food is digested (cholesteryl ester or cholesterol)
- the cholesterol and cholesteryl ester is broken down to free fatty acid and free cholesterol
- the free fatty acid goes straight into the intestinal cells, cholesterol being slightly charged need to be emulsified by bile acid from gallbladeder
- the cholesterol and bile acid form micelles which can now enter into the intestinal cell
- in the intestinal cell the cholesterol and free fatty acid join again to form chylomicrons
- the chylomicrons travel through the lymphatic channels into the blood
- from the blood into the liver
- in the liver chylomicrons are used to make bile acids and VLDL.
What are the four ways to intervene and control cholesterol
- lower cholesterol intake thru the diet-lower animal fat
- decrease cholesterol reabsorption in the intestine (small intestine) by using drugs like Ezetimibe
- decrease bile acid reabsorption by using bile acid sequestrants
- increase fiber: lower cholesterol absorption
What are bile salts and where are they stored
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
How is fibre used to lower cholesterol
fibre can bind to bile salts and cholesterol and stop reabsorption
How are sitostanol ester lower cholesterol
its from plants, similar in structure to cholesterol and stops cholesterol from entering micellar phase and reduces its adsorption into the blood stream
What is enterohepatic circulation
reabsorption of bile salts and cholesterol are transported back to the liver bound to albumin and recycled
What is an example of sitostaol ester
Benecol margarine
What are bile acid sequestrants
group of medications used for binding bile in the gastrointestinal tract–the bound cholesterol will then be lost in the stool
What are bile acids used to treat
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
Explain the mechanism of bile acid resins over all how does it effect the body
- bile acids will no be adsorbed again after resins are administered
- 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
- liver enzymes such as cholesterol 7 alpha-hydroxylase increases to form bile acids
- these bile acids will be transferred as usual to the gallbladder
- Overall, decrease in LDL-cholesterol
- Note: there will be an increase in VLDL-triglycerides
What is colestipol
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
How do bile acid resins work
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
When bile acid production increases, what also increases
an increase in production of VLDL
What do bile acid sequestrants affect the adsorption of
many types of drugs; lowers blood levels and therapy effectiveness. Also fat soluble vitamins because bile acids are not there to emulsify them
Name the three types of bile acid resins
- Cholestyramine (Questran)
- Colestipol (Colestid)
- Colesevelam (Welchol)
How many grams of cholestyramine should be take every day
4-6 grams/day
How many grams of Colestipol should be take per day
5-20 grams/dday
How many tablets of Colesevelam should be taken per day
6-7 tablets per day
How many grams are in each Colesevelam tablet
0.625 grams or 625 mg
How has the use of bile acid resin changed
there use has decreased mostly because of the effectiveness of statins; they are sometimes used as an adjunct to statins.
What is the benefit of bile acid sequestrants
lower coronary events and lack systemic toxicity
What is an important side effect of bile acid sequestrants
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
What are drug interactions
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
How can we work around drug interactions with bile acid
We can give other drugs 1 hour before of 4-6 hours after giving the resin
What are the uses of bile acid sequestrants.
Hint its 8 things
- primary hypercholesterolemia
- 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)
- diarrhea with excess fecal bile acids
- tropical diarrhea
- binding toxic agents, overdose of drugs, decrease adsorption of GI tract
- Pseudomembraneous colitis- major infection- broad spectrum antibiotics helps with symptoms
- lowers oxaluria- which is excessive calcium in the urine
Although this supplement is not fat soluble, how do bile acid resin impact it
folic acid is not fat soluble but the resin decrease its absorption so it need to be supplemented during drug therapy
Name the six toxic drugs that bile acid resins can decrease adsorption of
- phenobarbital
- warfarin
- Lindane
- lorazepam
- Methotrexate
- chlordecone
- digitoxin
What beneficial drugs are inhibited because of bile acid sequestrants- bind to
- thiazides (a few)
- furosemide
- propranolol
- L-thyroxine (levo-thyroxine)
- cardiac glycosides
- Coumarin anticoagulants
- statins
How is colestyramine packaged
its in individual packets or in bulk- the scoop measures out 4 grams/dose
What is a trick you can use to decrease indigestion with colestyramine
leave the water and powder suspended over night
How is colestipol packaged
its in bulk or individual packets of 5 gramss or a tablet as 1 gram
Colesevelam is packaged how
it only in tablet form (0.625 grams)
On page 5, what does the graph Effect of colesevalam on LDL-C display
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
Explain how the various lipoproteins are made in the body. See diagram on page 6
- VLDL is made in liver and broken down by lipoprotein lipase while circulating—-> the triglycerides go to tissues
- remnant is turned into IDL—> 50% goes to liver and the other half is broken down again by lipoprotein lipase to LDL
- 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%
Explain how cholesterol is endogenously synthesized
its made in the body
- acetyl CoA and acetoacetyl CoA combine to form 3-hydroxy-3 methyl glytaryl-CoA (HMG-CoA)
- HMG-CoA reductase enzyme will reduce this to mevalonic acid and continue to cholesterol
- Therefore statins will inhibit this step
What is the order of statins that will decrease the dose equivalence by decrease 25-30% in LDL
Peter Rose and Sam Love Pringles with flavor Pitavistatin Rosuvastin Atorvastatin Simvastatin Lovastatin Pravastatin Fluvastatin
What are the doses that will lower by 25-35% of LDL
2,5,10,20,40,40, 80mg
How to statins impact the body
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
Explain how LDL receptors work in the body
- the receptors will be exocytosed one the Apo B-100 bind to receptor on liver
- cholesterol inside the LDL will be used and the receptor recycled
