Dyslipidemias

Front 1

Functions of lipoprotein lipase

Back 1

i. Mediates several key steps of the cholesterol cycle.
ii. Hydrolyzes triglycerides in chylomicrons to make free fatty acids available to peripheral tissues.

Front 2

How is a patient's triglyceride level affected with a genetic deficiency of LPL?

Back 2

Patients with a genetic deficiency of LPL have extreme hypertriglyceridemia.

Front 3

Describe the role of the LDL receptor in the cholesterol cycle.

Back 3

i. Primary mediator of LDL clearance from the plasma.
ii. Located in hepatic and peripheral tissues.
iii. Binds LDL and IDL from the plasma through ApoB-100, resulting in metabolism of these lipoproteins.
iv. The hepatic LDL-receptor is up-regulated by low levels of cholesterol in the liver resulting in more clearance of plasma LDL when hepatic cholesterol stores are low. Plasma LDL thus decreases.

Front 4

LDL goal for High Risk: CHD or CHD risk equivalent

Back 4

<100 mg/dL (optional goal: <70 mg/dL)

Front 5

LDL goal for moderately high risk: 2+ risk factors

Back 5

<130 mg/dL
(optional goal of 100 mg/dL)

Front 6

LDL goal for moderate risk: 2+ risk factors

Back 6

<160 mg/dL

Front 7

HDL goal:

Back 7

>40 mg/dL

Front 8

Triglyceride goal

Back 8

<150

Front 9

MOA for fibric acid derivatives

Back 9

Activates peroxisome proliferator activated receptor alpha (PPAR-alpha)

Front 10

Lipid profile effects of fibric acid derivatives (aka fibrates)

Back 10

i. LDL: variable: ↓ 5-20% in many patients, but usually LDL increases in patients with very high triglycerides (i.e. >300 mg/dL).
ii. HDL: ↑10-35%
iii. Triglycerides: ↓ 20-50%

Front 11

Contraindications for fibric acid derivatives (aka fibrates)

Back 11

i. Pre-existing gallbladder disease
ii. Hepatic dysfunction
iii. Severe renal impairment

Front 12

Precautions for fibric acid derivatives (aka fibrates)

Back 12

i. Cholelithiasis
ii. Concomitant use of statins

Front 13

Drug interactions for fibric acid derivatives (AKA fibrates)

Back 13

i.Statins
ii.Ezetimibe (Zetia®)
iii.Glyburide (Micronase®, Diabeta®) and repaglinide (Prandin®)

Front 14

Adverse effects for fibric acid derivatives (AKA fibrates)

Back 14

i. Gallstones
ii. Myopathy
iii. Increased LFT’s

Front 15

Real world application for fibric acid derivatives

Back 15

i. Fibrates are first line therapy for treatment of high triglycerides. No agent lowers triglycerides more than fibrates. Niacin can lower them comparably.
ii. Caution must be used if these agents are combined with statins.
iii. Trilipix® (delayed release fenofibrate) was approved in December 2008 with an indication to be used with a statin.
iv. Administration: gemfibrozil twice daily with meals, fenofibrate once daily without regard to meals.
v. Watch for increases in LDL following initiation, especially in patients with very high triglycerides at baseline.

Front 16

MOA for bile acid sequestrants

Back 16

i. Bile acids, metabolites of cholesterol, are normally largely reabsorbed in the jejunum and ileum. They are then returned to the cholesterol cycle. Bile acid sequestrants are resins that complex with these bile acids preventing reabsorption. A negative feedback loop in the liver recognizes a decreased amount of bile acids resulting in increased hepatic uptake and catabolism of LDL, and thus lower levels of LDL.

Front 17

Lipid profile effects of bile acid sequestrants

Back 17

i. ↓ LDL 15-30%
ii. ↑ HDL 3-5%
iii. ↑ Triglycerides 0 to ~10%

Front 18

Contraindications for bile acid sequestrants

Back 18

i. Bowel obstruction
ii. Complete biliary obstruction
iii. Hypersensitivity

Front 19

Precautions for bile acid sequestrants

Back 19

i. Malabsorption disorders (particularly disorders of fat soluble vitamin absorption)
ii. Chronic constipation
iii. Triglycerides > 200 mg/dL

Front 20

Drug interactions for bile acid sequestrants

Back 20

i. BAS’s bind many/most drugs (too many to list) and impair absorption to varying degrees. Cholestyramine and colestipol are highly charged and have a strong binding affinity to anionic drugs. Colesevelam is not highly charged and appears to impair absorption of other drugs considerably less (or none at all).
ii. The effect is most clinically relevant for drugs that have a narrow therapeutic window, such as warfarin.
iii. The solution to this effect is to separate dosage of BAS’s from other drugs. This means other drugs should be taken 1 hr before or 4-6 hrs after a BAS. BAS drugs are administered 1-2 times/day.

Front 21

Adverse reactions for bile acid sequestrants

Back 21

i. Constipation/flatulence/bloating (infrequent with colesevelam)
ii. Steatorrhea
iii. Increased triglyceride concentration
iv. Malabsorption of fat soluble vitamins

Front 22

Real world info for bile acid sequestrants

Back 22

i. Side effects, drug interactions, and tablet burden result in the infrequent use of this class of agents.
ii. Colesevelam is preferred, due to less frequent drug interaction and reduced frequency of adverse effects.
iii. These drugs can be used in combination with statins.
iv. Have some glycemic reduction properties and are being used in some diabetics for this purpose.