Pharm Lecture 5: Hyperlipidemia

Front 1

Which is good kind of lipoproteins?

Back 1

HDL

Front 2

Which is the greatest contributor to atherosclerosis?

Back 2

LDL

Front 3

Which probably contributes to atherosclerosis?

Back 3

VLDL

Front 4

major lipid core of three lipoproteins

Back 4

VLDL- trigs
LDL-cholesterol
HDL- cholesterol

Front 5

jobs of three lipoproteins

Back 5

VLDL- delivers trigs to non hepatic tissue
LDL- delivers cholesterol to nonhepatic tissue
HDL-transport cholesterol back to liver

Front 6

optimal levels of LDL, HDL, total chol?

Back 6

LDL: < 100
HDL: >=60: high
total: < 200

Front 7

six kinds of pharmacotherapy for hyperlipidemia

Back 7

HMG-CoA reductase inhibitors (Statins)
Fibrates
Niacin, Nicotinic acid
Bile acid sequestrants
Cholesterol absorption inhibitors
Omega-3 fatty acids

Front 8

statins MOA

Back 8

Inhibition of HMG-CoA reductase, whereby reducing cholesterol synthesis
Increasing the number of LDL receptors on hepatocytes, whereby  removal of LDL from the blood
Most effective drugs for lowering LDL

Front 9

statins nonlipid beneficial actions

Back 9

Promote plaque stability
Reduce inflammation at plaque site
Improve endothelial function

Front 10

should give statin when?

Back 10

evening

Front 11

dosage reduction for rosuvastatin in whom?

Back 11

Asian patients, untreated hypothyroidism, or anyone over 65

Front 12

statins AEs

Back 12

GI upset, rash, headache
Hepatotoxicity
Rhabdomyolysis
Acute renal failure

Front 13

statins DIs

Back 13

Increased risk of myopathy & rhabdomyolysis with fibrates, niacin and colchicine
Increased risk of liver failure with fibrates, niacin, ezetimibe & drugs that can cause hepatotoxicity.
Increased risk of renal failure with drugs that can cause renal damage.
CYP3A4 inhibitors (e.g. grapefruit juice, amiodarone, -azole antifungals, macrolide antibiotics) raise some statin levels.
CYP3A4 inducers (e.g. phenytoin) may decrease some statin levels.

Front 14

statins monitoring

Back 14

Lipid Panel: TC, TG, LDL, HDL
Liver enzymes: ALT/AST
Ok if <3x ULN
Creatinine Kinase
Only if patient develops muscle symptoms
Discontinue CK is >10x ULN
May continue if patient is asymptomatic and small CK elevation

Front 15

statins CIs

Back 15

Pregnancy (Category X)
Breast feeding
Active liver disease
Persistent elevations of serum transaminases
Concurrent use of potent inhibitors of metabolism (for some statins)

Front 16

temporarily d/c statin in:

Back 16

serious illness, trauma, or major surgery

Front 17

fibrates (fibric acid derivatives)

Back 17

Gemfibrozil (Lopid®) 600 mg BID

Fenofibrate (micronized)
Antara® 43-130 mg QD
Lofibra Caps® 67-200 mg QD

Fenofibrate
Tricor® 48-145 mg QD
Fenoglide® 40-120 mg QD
Lofibra Tabs®) 54-160 mg QD

Fenofibric acid
Trilipix® 45-135 mg QD
Fibricor® 35-105 mg QD

Front 18

fibrates MOA

Back 18

Peroxisome proliferator-activated receptor alpha (PPAR-α) agonist
Downregulates apoprotein C-III which inhibits lipoprotein lipase activity
Increased catabolism of VLDL and TG-rich particles
Decrease in TG alters LDL from small, dense particles (atherogenic) to large, buoyant particles (higher affinity for cholesterol receptors, more rapidly catabolized)
Also Increases synthesis of apoprotein A-I which transports fatty acids
The most effective drugs at lowering TGs.

Front 19

fibrates SEs

Back 19

Abdominal pain
Cholelithiasis
Rhabdomyolysis
Liver Failure
Blood dyscrasias

Front 20

fibrates DIs

Back 20

Statins
Warfarin
Repaglinide (Starlix®) contraindicated with gemfibrozil since strong 2C8 inhibitor, caution with others (monitor glucose)
Bile acid sequestrants

Front 21

fibrates CIs

Back 21

severe hepatic/renal dysfunction
gallbladder dz

Front 22

fibrates monitoring, periodic

Back 22

Lipid panel
Baseline renal function
LFTs
CBC

Front 23

Dose adjust fenofibrate in

Back 23

elderly

Front 24

nicotinic acid (niacin) MOA

Back 24

Exact mechanism unknown
Inhibits the synthesis of VLDL and LDL
Inhibits mobilization of free fatty acids from peripheral adipose tissue to the liver
Vasodilation at large doses
Increases HDL levels better than any other drug

Front 25

niacin SEs

Back 25

Skin (flushing, itching)
Gastrointestinal upset (nausea, heartburn, peptic ulcers)
Hepatotoxicity
Hyperglycemia, hyperuricemia

Front 26

niacin precautions

Back 26

gout, DM

Front 27

niacin CI

Back 27

Hepatic dysfunction
Active ulcer disease
History of serious hemorrhaging
Severe gout

Front 28

niacin DIs

Back 28

Statins
Increase risk of myopathy
Bile acid sequestrants decrease absorption

Front 29

niacin monitoring

Back 29

Lipid panel
Baseline LFTs, then every 6-8 wks
Baseline uric acid and glucose, then after stabilization

Front 30

bile acid sequestrants

Back 30

Cholestryamine (Questran®/Questran light®)
Colestipol (Colestid®)
Colesevelam (Welchol®)

Front 31

bile acid sequestrants MOA examples

Back 31

Exchange chloride ions for bile acids in the intestine, thus inhibiting reabsorption of bile acids in terminal gut
Disrupt the normal enterohepatic re-circulation of bile acids from the intestinal lumen to the liver
Convert hepatocellular cholesterol into bile acids

Front 32

note about bile acid sequestrants

Back 32

should be taken with food

Front 33

bile acid sequestrants SEs

Back 33

Constipation, nausea, cramping, bloating, flatulence, taste intolerability, hypertriglyceridemia

Front 34

bile acid sequestrants CIs

Back 34

Relative: TG>300 mg/dL
Absolute: TG>500 mg/dL
Absolute: Bowel or biliary obstruction, hypertriglyceridemia-induced pancreatitis, dysbetalipoproteinemia

Front 35

bile acid sequestrants DIs

Back 35

Agents w/ bioavailability <80%
Fat soluble vitamins, statins, folic Acid (reduced absorption)
NTI drugs (reduced absorption, decreased therapeutic effects): e.g. warfarin, digoxin, thyroid hormone, antiseizure, oral contraceptives, cyclosporin
Recommendation is to administer 4 hours prior to BAS

Front 36

bile acid sequestrants monitoring

Back 36

lipid panel
TG
PT

Front 37

selective cholesterol absorption inhibitor MOA and example

Back 37

Acts on cells of the brush border of the small intestine to inhibit cholesterol absorption. It blocks absorption of dietary cholesterol & cholesterol secreted in the bile.
Results in decreased delivery of cholesterol to the liver, reduction of hepatic cholesterol stores and increased clearance of cholesterol from the blood
Has been shown to improve lipid profiles, but impact on coronary events & mortality has NOT been established.
Zetia

Front 38

ezetimibe SEs

Back 38

Diarrhea, abdominal pain, arthralgias, cough, fatigue
Rhabdomyolysis
Pancreatitis
Increased LFTs

Front 39

ezetimibe DIs

Back 39

Fibrates may ↑ ezetimibe concentrations & hepatobiliary SEs
Bile acid sequestrants can ↓ ezetimibe absorption
Warfarin
Statins (↑ LTFs)
Cyclosporine (↑ levels of both)

Front 40

ezetimibe CIs

Back 40

hepatic insufficiency

Front 41

ezetimibe monitoring

Back 41

lipid panel
LFTs

Front 42

Ezetimibe Pearls

Back 42

Relatively few drug interactions
No effect on fat soluble vitamins
Some increases in LFTs
Initiate after statin is maximized
Has been shown to improve lipid profiles, but impact on coronary events & mortality has NOT been established.

Front 43

Omega-3 FAs MOA

Back 43

Reduce hepatic triglyceride production and increase triglyceride clearance
Modestly increases plasma levels of LDL cholesterol and increase HDL cholesterol levels

Front 44

Omega-3 FAs indication

Back 44

Adjunct to diet for hypertriglyceridemia; withdraw if no response in 2 months.
Each capsule contains eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)

Front 45

omega 3 FAs example

Back 45

Lovaza

Front 46

omega 3 FAs SEs

Back 46

fishy taste, rash, eructation, dyspepsia, taste perversion, allergic reaction

Front 47

omega 3 FAs DIs

Back 47

drugs that may enhance bleeding

Front 48

Omega-3 Fatty Acids Pearls

Back 48

Total EPA and DHA dose recommended for TG lowering is ~2–4 g/day
Patients concomitantly taking aspirin, clopidogrel, and/or warfarin may be at increased risk of bleeding
Refrigeration may help alleviate fishy taste
In patients with TG >500 mg/dl, ~4 g/day of EPA and DHA can significantly reduce TG and VLDL levels, but may increase LDL levels