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Flashcards in Dyslipidemia Deck (20)
0

Classification of dyslipidemia

1. Primary or familial
2. Secondary or acquired: diet, drugs, diseases, disorders in altered states of metabolism

1

Drugs that cause elevated LDL and triglyceride

LDL: diuretics, cyclosporine, tacrolimus, glucocorticoids, Amiodarone

Triglycerides: oral estrogen, glucocorticoids, bile acid resins, protease inhibitors, anabolic steroids, sirolimus, raloxifene, tamoxifen, beta blockers, thiazides, atypical antipsychotics, alpha interferons, propofol

2

4 key groups of patients that need statins

1. Clinical ASCVD, including (CHD, S/P MI, stable/unstable angina, coronary or arterial revascularization, stroke, TIA, PAD): HIGH IF 75 yo
2. LDL >\= 190: HIGH INTENSITY
3. Diabetes and 40-75 years of age with LDL between 70-189: HIGH
4. 40-75 years of age with LDL between 70-189 and an estimated 10 yr risk of ASCVD of >\= 7.5%: MODERATE TO HIGH
5. <\= 7.5 risk vs benefit

3

Other risk factors to consider

LDL >\= 160 with genetic hyperlipidemia

Family hx of premature ASCVD (2

Coronary artery calcium score >\= 300

Ankle brachial index <0.9

4

Parts of ASCVD assessment tool

Gender, age (40-79), race (white/black), total cholesterol, HDL, systolic BP, BP meds, diabetes, and smoking status

5

High intensity statin

Response: dec LDL by ~50%

Atorvastatin 40-80mg daily
Rosuvastatin 20-40 mg daily

6

Moderate intensity statin

Response: dec LDL by 30-49%

Atorvastatin (Lipitor) 10-20mg
Rosuvastatin (Crestor) 5-10mg
Simvastatin (Zocor) 20-40mg
Pravastatin (Pravachol ) 40-80 mg
Lovastatin (mevacor, altoprev) 40 mg
Fluvastatin XL (lescol XL) 80mg
Fluvastatin 40 mg BID
pitavastatin (Livalo) 2-4mg daily

7

Statin considerations

MOA: inhabit the enzyme HMG Kalaiwa reductase preventing the conversion of HMG Coatue to mevalonic the rate limiting step and cholesterol synthesis

Hepatotoxicity is a major concern: stop if AST or ALT become greater than three times the upper limit of normal

If muscle symptoms: discontinue statin and see if the symptoms go away. If symptoms resolve and if no contraindication restart the same Statin at the same or lower dose. If pain returns discontinue and choose a different statin once symptoms resolve

Contraindications: active liver disease, pregnancy, breast-feeding, concurrent use of strong 3A4 inhibitors

Warnings: skeletal muscle effects

If diabetes: can increase A1C and fasting blood glucose

Side effects: myalgias, arthralgias, myopathy, diarrhea, increased CPK, rhabdomyomalysis, cognitive impairment, increased blood glucose and A1C, possible increased risk of cataracts, increased LFTs

Notes: pregnancy category X, can take Crestor, Lipitor, Livalo, Lescol and Pravachol at any time of day

Effects: dec LDL (~20-55%), inc HDL (~5-15%), dec TG (~10-30%)

8

Combo statin products

Atorvastatin + amlodipine: Caduet
Atorvastatin + ezetimibe: Liptruzet

Simvastatin +ezetimibe: vytorin
Simvastatin + niacin: simcor
Simvastatin + sitagliptan: juvisync

Lovastatin + niacin: adicor

9

Interactions

Avoid use of statins with gemfibrozil and niacin due to inc in conc and inc risk of myopathies

10

Simvastatin, lovastatin, and atorvastatin

Major 3A4 substrates

Simvastatin: avoid 80mg per day due to myopathy
1. Do not exceed 10mg/day with verapamil, diltiazem, or dronedarone
2. 20mg/day with Amiodarone, amlodipine, or ranolazine

Lovastatin:
1. 20mg/day: danazol, diltiazem, verapamil, dronedarone
2. 40mg/day: Amiodarone

Atorvastatin: avoid with cyclosporine, tipranivir plus ritonavir or telapravir.

Digoxin levels may inc with statins

11

Rosuvastatin, pravastatin, fluvastatin

Cyclosporine can inc their levels

12

Pitavastatin

Few Cyp interactions but contraindicated with cyclosporine

13

Strong 3A4 inhibitors: avoid with simvastatin and lovastatin

Itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, protease inhibitors, telaprevir, cyclosporine, gemfibrozil, grapefruit juice

14

Ezetimibe

MOA: inhibits absorption of cholesterol in small intestines

Warning: avoid using moderate or severe hepatic impairment; skeletal muscle effects when combined with a Statin

Side effects: URTIs, diarrhea, arthralgias, myalgias, pain in extremities, sinusitis

Monitoring: liver function test at baseline and clinically thereafter

Notes: pregnancy category C; clinical trial show a decrease in Elidio but no reduction in clinical outcomes

Effects: LDL-18-23%; HDL 1-3%; TG 8-10%

15

Bile acid sequestrants

MOA: binds bile acids in the intestine forming a complex that is excreted in the feces

Drugs: cholestyramine, colesevelam (welchol), colestipol (Colestid)

Contraindication: bowel exception or biliary obstruction

Side effects: constipation, dyspepsia, nausea, abdominal pain, cramping, gas, bloating, hypertriglyceridemia, esophageal attraction, increased LFTs

Notes: pregnancy category B, may decrease LDL by 10 to 30% and increase HDL by 3 to 5% but may increase triglycerides

16

Bile acid sequestrants drug interactions

Cholestyramine and colestipol, separate all other drugs by 1-4 hours before or 4-6 hours after

Take the following medications four hours prior to welchol: cyclosporine, oral contraceptives, levothyroxin, olmesartan, phenytoin, sulfonylureas and tetracyclines

May decrease the absorption of fat soluble vitamins, folic acid and iron (separate from any multivitamin)

17

Fibrates

MOA: Ppar Alpha activators leading to enhanced elimination and decreased synthesis of VLDL causing a decrease in triglycerides and increasing HDL

Drugs: fenofibrate (TriCor, Trilipix); gemfibrozil (lopid)

If dec TG a lot could inc LDL

18

Niacin

MOA: decrease the rate of hepatic synthesis of VLDL the Sadik Reese and triglycerides and LDL and may increase the rate of triglyceride removal from plasma

AKA: nicotinic acid or vitamin B3

Side effects: Flushing, pleuritis, nausea, vomiting, diarrhea, G.I. distress, hyperglycemia, hyperuricemia, increased cough, hepatotoxicity, orthostatic hypertension, hypophosphatemia

Notes: pregnancy category C; me at least nice and has poor colorability due to Flushing and itching but extended release forms have less therefore the best clinical choices Niaspan which it has less flushing and less hepatotoxicity but is more expensive

Niaspan: take it bedtime after a low-fat snack; less associated with adverse effects

19

Lomitapide (Juxtapid)

New agent for familial homozygous hypercholesterolemia

MOA: Binds to and inhibits microsomal triglyceride transfer protein in the endoplasmic reticulum dust preventing the assembly of Apo-b containing lipoprotein's in the enterocytes and hepatocytes resulting in reduced production of chylomicrons and VLDL and subsequently reduced plasma LDL

Blackbox warning: hepatotoxicity

Contraindications: pregnancy; moderate or severe hepatic impairment; active liver disease

Pregnancy category X