Dyslipidemia Flashcards
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
Classification of dyslipidemia
- Primary or familial
2. Secondary or acquired: diet, drugs, diseases, disorders in altered states of metabolism
4 key groups of patients that need statins
- Clinical ASCVD, including (CHD, S/P MI, stable/unstable angina, coronary or arterial revascularization, stroke, TIA, PAD): HIGH IF 75 yo
- LDL >= 190: HIGH INTENSITY
- Diabetes and 40-75 years of age with LDL between 70-189: HIGH
- 40-75 years of age with LDL between 70-189 and an estimated 10 yr risk of ASCVD of >= 7.5%: MODERATE TO HIGH
- <= 7.5 risk vs benefit
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
Parts of ASCVD assessment tool
Gender, age (40-79), race (white/black), total cholesterol, HDL, systolic BP, BP meds, diabetes, and smoking status
High intensity statin
Response: dec LDL by ~50%
Atorvastatin 40-80mg daily
Rosuvastatin 20-40 mg daily
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
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%)
Combo statin products
Atorvastatin + amlodipine: Caduet
Atorvastatin + ezetimibe: Liptruzet
Simvastatin +ezetimibe: vytorin
Simvastatin + niacin: simcor
Simvastatin + sitagliptan: juvisync
Lovastatin + niacin: adicor
Interactions
Avoid use of statins with gemfibrozil and niacin due to inc in conc and inc risk of myopathies
Simvastatin, lovastatin, and atorvastatin
Major 3A4 substrates
Simvastatin: avoid 80mg per day due to myopathy
- Do not exceed 10mg/day with verapamil, diltiazem, or dronedarone
- 20mg/day with Amiodarone, amlodipine, or ranolazine
Lovastatin:
- 20mg/day: danazol, diltiazem, verapamil, dronedarone
- 40mg/day: Amiodarone
Atorvastatin: avoid with cyclosporine, tipranivir plus ritonavir or telapravir.
Digoxin levels may inc with statins
Rosuvastatin, pravastatin, fluvastatin
Cyclosporine can inc their levels
Pitavastatin
Few Cyp interactions but contraindicated with cyclosporine
Strong 3A4 inhibitors: avoid with simvastatin and lovastatin
Itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, protease inhibitors, telaprevir, cyclosporine, gemfibrozil, grapefruit juice
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%
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
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)
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
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
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
