Lipid-Lowering Medications

Question 1

Cholesterol recommendations:

Answer 1

Total <200
LDL <100
HDL 35-100

Question 2

What is the MOA of HMG CoA Reductase Inhibitors?

Answer 2

These drugs inhibit HMG CoA Reductase which is responsible for the rate limiting step in the body’s natural production of cholesterol in hepatocytes. By inhibiting the biosynthesis of cholesterol there is an upregulation in LDL receptor expression in hepatocytes which increases uptake of plasma LDL into the hepatocytes and out of the systemic circulation

Question 3

What are the HMG CoA Reductase Inhibitors in order of most potent to lease:

Answer 3

Rosuvastatin 
Atorvastatin 
Simvastatin 
Pravastatin 
Lovastatin 
Fluvastatin

Question 4

AE of HMG CoA inhibitors:

Answer 4

Myopathy, myositis, rhabdomyolysis
Elevated transaminases

Monitor CK, transaminases, muscle ache complaints

Question 5

What do atorvastatin, simvastatin, and lovastatin have in common?

Answer 5

They are all metabolized by CYP 3A4

Ex- Rotanavir is a potent CYP 3A4 inhibitor which can lead to toxic levels of simvastatin and lovastatin causing an increased risk for rhabdomyolysis

Question 6

Cholestyramine, Colesevelam, and Colestipol are all:

Answer 6

Bile acid sequesterants

Question 7

What is the MOA of bile acid sequesterants?

Answer 7

Cationic polymer resins that bind (noncovalent) to negatively charted bile acids in the small intenstine. The complex cannot be reabsorbed in the distal ileum and is excreted in the stool.
A decrease in the reabsorption of bile acids by the ileum partially interrupts enterohepatic bile acid circulation.
Hepatocytes up-regulate 7a-hydroxylase, the rate limiting step in bile acid synthesis.
The increase is bile acid synthesis decreases hepatocyte cholesterol concentration, LDL receptors increase, LDL clearance from the circulation increases

Question 8

When should doses of bile acid sequesterants be administered?

Answer 8

After meals (frequent dosing)

Question 9

Most AE of bile acid sequesterants are related to:

Answer 9

GI upset: bloating, dyspesia

Question 10

How can some drug interactions be avoided with bile acid sequesterants?

Answer 10

To avoid binding with other drugs, separate dosing (1-2hrs to avoid)

Question 11

MOA of Cholesterol Absorption Inhibitors:

Answer 11

Reduction of cholesterol absorption by the small intestine

This could cause increase in hepatic synthesis; often used in combination with another agent (statin)

Question 12

Cholesterol Absorption Inhibitors include:

Answer 12

Ezetimibe (manufactured)
Plant sterols (veg, fruit, supplements)

Question 13

What effect do Fibrates have on cholesterol/triglycerides?

Answer 13

Increase HDL

Decrease Triglyceride synthesis

Question 14

Fibrates include gemibrozil, fenofibrate, clofibrate. What are their AE:

Answer 14

GI discomfort
Increased transaminases
Myopathy, arrhythmia (rare)

*use with caution with statins d/t similarities in AE.

Question 15

Two drug interactions that fibrates have include:

Answer 15

Fibrates displace warfarin from albumin increases free warfarin and raising INR
Fibrates increase cyclosporine clearance

Question 16

What time of day should most statins be taken?

Answer 16

At bedtime

Question 17

How do fibrates work?

Answer 17

They bind to and activate PPARa which is a nuclear receptor expressed in hepatocytes, sk. muscle, macrophages, and the heart->affects lipid metabolism= increased HDL and decreased triglyceride synthesis.

Question 18

What is niacin most effective at doing?

Answer 18

Increasing HDL

Also decreases triglycerides and LDL

Question 19

What is the most common side effect of Niacin and how can it be prevented?

Answer 19

Cutaneous flushing (release of prostaglandins w/in the skin)
To avoid pretreat 30mins before with NSAIDS or ASA
SR can also decrease flushing 

This side effect dissipates with time

Question 20

Other AE of Niacin include:

Answer 20

Pruritis
Hyperuricemia
Myopathy (rare, but use caution with fibrates and statins)
Impaired insulin sensitivity

Question 21

How do Omega-3 Fatty Acids affect the body?

Answer 21

Reduce triglyceride biosynthesis and increased fatty acid oxidation in the liver

(these include fish oils, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA))
(Required 2-4grams/day to be effective, if no effect seen in 2months discontinue)

Question 22

If a person has high triglycerides which lipid lowering medication may be CI?

Answer 22

Bile acid sequesterants; they could actually increase TG

Question 23

What are the statin benefit groups:

Answer 23

1. Clinical ASCVD
(21-75= high)  
(>75= moderate)
2. LDL =>190mg/dL
(high) 
3. 40-75 y.o. with DM and LDL 70-189mg/dL 
(mod-high)
4. 40-75 y.o. without clinical ASCVD or DM with LDL 70-189mg/dL and est. 10-year ASCVD risk of =>7.5%
(mod-high)

Question 24

Which two statins are known as ‘high intensity statins’

Answer 24

Atorvastatin
Rosuvastatin
(at high doses)

Question 25

Niacin blocks_______ in adipose tissue to reduce _______

Answer 25

lipase

plasma free fatty acids