Dyslipidemia

Front 1

LDL and atherosclerosis

Back 1

-excess LDL --> intima of blood vessels --> chemically modified creating free radicals that change ApoB100 on LDL; scavenger receptors on macrophages and other cells accumulate oxidized LDL --> foam cells --> release free radicals, incite inflammation and form major parts of atherosclerotic plaques

Front 2

mgmt of dyslipidemia

Back 2

-LDL is primary target of tx
-HMG CoA reductase inhibitors (statins)- first line agents to lower LDL
-once LDL target is met can look at other aspects like HDL, TG
-TG mostly affected by diet
-Use therapeutic lifestyle changes (TLC), dietary options, exercise in addition to drug therapy!
-in high risk pts start meds ASAP

Front 3

LDL goals

Back 3

1. CHD or CDH risk equivalent <100
2. >/= 2 Risk factors
-10 yr risk 10-20% moderately high risk <100; consider drugs >100
-10 yr risk <10%l consider drugs >160
3. <2 risk factors <160

Front 4

high risk pts

Back 4

-CHD, DM, PAD/carotid artery stenosis and 2 more more risk factors that give them <20% risk of having an MI within 10 yrs
-tx goal is LDL <100 but very high risk pts consider <70

Front 5

high triglycerides or low HDL in high risk pts...

Back 5

-add fibrates or nicotinic acid to LDL lowering drug

Front 6

Major risk factors that modify LDL goal

Back 6

1. smoking
2. HTN
3. HDL <40
4. FH (CHD in make first degree relative <55yrs or in female first-degree relative <65yrs)
5. Age (men >/=45 yrs; women >/=55yrs)

Front 7

Steps in mgmt of a pt with dyslipidemia

Back 7

1: determine LDL, TC, HDL
2. Identify if pt is high risk for CHD or risk equivalent
3: assess major risk factors that modify LDL goal
-if 2+ risk factors asses 10yr CHD risk
-determine risk category

Front 8

If LDL is above goal

Back 8

1. initiate TLC for all rish categories
2. Add drug + TLC to CDH/CHD equivalent group is LDL >100
3. Treat metabolic syndrome and elevated TGs
4. Non HDL goal (once the LDL goal is met and with high triglycerides)

Front 9

Progression of drug therapy for LDL-C lowering

Back 9

Visit 1: initiate LDL-lowerig drug therapy-> start Statin
Visit 2: if LDL goal not achieved intesify LDL-lowering therapy -> consider high dose of statin or add a bile acid resin or nicotinic acid
Visit 3: if LDL goal not acheived, drug therapy or refer to a lipid specialist -> if LDL goal achieved, tx other lipid risk factors
F/U q4-6mo: monitor response and adherence to therapy

Front 10

Metabolic syndrome (3+ risks)

Back 10

1. abd obesity (wait circumference)
-men >40in
women > 35in
2. TG >150
3. HDL
-men <40
-women <50
4. BP >130/85
6. Fasting glucose >110

Front 11

Triglycerdies

Back 11

-nml <150
-high 200-499
-very high >500 (can lead to pancreatitis)
-overwt, excessive EtOH, inactivity, insulin resistance, DM, genetic factors, smoking, renal diseases can all lead to high TG

Front 12

dyslipidemia drugs

Back 12

1. HMG-CoA reductase inhibitors (Statins)- most effective in lowering LDL
2. Bile acid sequestrants
3. Nicotinic acid
4. Fibric acid derivatives
5. Cholesterol absorption inhibitor

Front 13

The "statins"

Back 13

-lowers LDL
-Atorvastatin (Lipitor)-most potent
-Rosuvastatin (Crestor)- very potent
-Fluva, Lova, Prava, Simva
-decrease MI, CVA, and PAD, primary and secondary prevention of atherosclerosis

Front 14

Livalo (pitavastatin)

Back 14

-newest statin
-is only minimally metabolized by the liver though the C-P450 pathway
-few issues with D/I

Front 15

Statins MOA

Back 15

-inhibit hepatic enzyme HGM CoA reductase --> rate limiting step in cholesterol biosynthesis --> less cholesterol --> increased LDL receptors to increase LDL removal from circulation

Front 16

AE of Statins

Back 16

1. increased liver enzymes (stop therapy if AST and ALT >3 times UNL)
2. myopathy with elevated CK- monitor for muscle tenderness, soreness and weakness
-Rhabdomyolysis (rare)
-DI --> caution with fibrates and nicotinic acid

Front 17

Statins C/I in

Back 17

1. pregnancy
2. Nursing mothers
3. pts with active liver disease

Front 18

Statins + fibrates

Back 18

-may be associated with a greater risk of myopathy and rhabdomyolysis
-myopathy risk enhanced with:
1. high doses of statins
2. renal insufficiency
3. concomitant meds: itraconazole, ketoconazole, cyclosporin A, erythromycni
4. >70 yrs

Front 19

Statins- therapeutics

Back 19

-risk stratify and obtain fasting lipid panel and baseline LFTs
-If LDL level is moderately elevated (above goal) start at standard dose – if very high start higher dose
-Repeat fasting lipids in 6 weeks and if not at goal increase dose --> RTO 6 weeks and still not at goal consider adding another drug (BAS or nicotinic acid)
-LFTs at 12 weeks and annually thereafter

Front 20

Bile acid sequestrants (BAS)

Back 20

-MOA: lower LDL by binding bile acids -->less cholesterol to liver --> increased LDL receptors --> lower LDL
-15-30% reduction in LDL
-TG no effect or increase

Front 21

BAS AE and DI

Back 21

AE: GI, constipation, bloating, fullness, N, flatulence
-do not use in pts with high TG levels

DI: lack systemic toxicity; decrease absorption of many drugs so take other meds 1 hr before or 4 hrs after

Front 22

BAS/BARs

Back 22

1. Colesevelam- best tolerated (cat B)
2. Cholestyramine poweders
3. Colestipol (powder and tabs) (cat C)
-used as combo therapy and preg women

Front 23

Nicotinic Acid or NIacin

Back 23

-MOA: inhibits production of VLDL by liver, increases HDL production by increasing Apo A I; inhibits free fatty acid release from adipose tissue
-HDL inc 15-35%
-LDL dec 5-25%
-TG dec 20-50%
-reduce risk of recurrent MI & mortality

Front 24

Niacin AE

Back 24

-MANY
-flushing and HA: take aspirin 30 min before first daily dose to limit these sx
-N, dyspepsia, diarrhea and activation of PUD
-hepatotoxicity
-hyperuricemia
-hyperglycemia
-dose niaspan at bedtime to reduce AE

Front 25

Nicotinic acid derivatives CI and DI

Back 25

CI:
-chronic liver disease
-severe gout
-relative: DM and hyperuricemia

DI: caution with statins for myopathy

-preg cat C, dc when nursing

Front 26

Nicotinic acid- monitoring

Back 26

-baseline LFTs, uric acid, and FBS then 6-8 wks after therapy and as needed or at least annually
-available preps:
1. extended release nicotinic acid (Niaspan)
2. Crystalline nicotinic acid (OTC)

Front 27

Fibric Acid derivatives (Fibrates)

Back 27

-primary use is to lower TG
-combo therapy with statins to improve overall lipid profile
-Gemifibrozil
-Fenofibrate
-Clofibrate

Front 28

Fibrates MOA

Back 28

-Complex but may be agonists for nuclear transcription factor PPAR-alpha which alters transcription leading to decreased TG levels and secondary increases in HDL
-dec TG by 25-50%
-HDL 10-15% inc

Front 29

Fibrates AE

Back 29

-GI most common
-increase choleslithiasis
-renal excretion
-cat C
-interactions: monitor INH in pts on warfarin, inc risk of myopathy with statin and in renal pts

Front 30

Ezetimibe (Zetia)

Back 30

-Used alone with diet and in combination with statin therapy to lower TC, LDL-C
-MOA: inhibits intestinal absorption of cholesterol at the brush border
-AE: Slightly higher incidence of elevated liver enzymes with combo therapy
-preg cat C

Front 31

Vytorin

Back 31

-ezetimibe with simvastin
-oral

Front 32

Combination therapy

Back 32

-statins most effective for LDL lowering- max this first
-Zetia is controversial
-Niacin improves HDL, TG, and LDL
-BAS can be added to statin but not well tolerated
-Fibrates-mainly used to lower TG and improve atherogenic dyslipidemia *

Front 33

Concerns with combo therapy

Back 33

-Statin-fibrate combo therapy may increase risk for myopathy

Front 34

Omega 3 Fatty acids

Back 34

- Lovaza
-indicated as an adjunct to diet to decrease triglyceride levels of adults with very high triglyceride