Dyslipidemia Flashcards
Drugs/conditions that raise LDL and TG
- Diuretics
- Efavirenz
- Steroids
- Immunosuppressants (cyclosporine, tacrolimus)
- Atypical antipsychotics (aripiprazole, quetiapine, olanzapine, risperidone)
- Protease inhibitors
Drugs that raise LDL only
Fish oils (except Vascepa)
Drugs that raise TG only
- IV lipid emulsions
- Propofol
- Bile acid sequestrants
Conditions that raise LDL and TG
- Obesity, poor diet, hypothyroidism, alcoholism, smoking, diabetes, renal/liver disease, nephrotic syndrome
Classification of cholesterol and TG levels
- Non-HDL: <130 (desirable)
- LDL: <100 (desirable), >=190 (very high)
- HDL: >=40 (men), >=50 (women)
- TG: <150 (desirable), >=500 (very high)
(>=): more than or equal to
Friedewald equation
LDL = TC - HDL - TG/5
**This formula is not used when the TGs are > 400 mg/dL
What factors included to calculate ASVD risk within the next 10 years?
Factors to calculate ASCVD risk:
* Gender, age (20-79 years), race
* TC and HDL
* SBP and whether antihypertensive tx
* The presence of diabetes and smoking
Notes:
– Should be repeated every 4-6 years
– The risk score is NOT needed for pts with ASVD, diabetes or LDL>=190
Which drugs should not be used if the AST or ALT is >3 times upper limit of normal?
- Niacin
- Fibrates
- Potentially statins
- Ezetimibe
What is the rate limiting step in cholesterol synthesis and what does statins do?
- Statins inhibit the HMG-CoA reductase which prevents it to convert into mevalonate. This is the rate limiting step.
Which patient population needs high intensity statin?
- Clinical ASCVD (CHD, stroke, TIA or peripheral artery disease
- Primary elevation of LDL >=190 mg/dL
- Diabetes and age 40-75 years with LDL between 70-189 mg/dL (multiple ASCVD risk factors)
- Age 40-75 years with LDL between 70-189 mg/dL (10-year ASCVD risk >=20%)
Which patient population needs moderate intensity statin?
- Diabetes and age 40-75 years with LDL between 70-189 mg/dL (regardless of 10-year ASCVD risk)
- Age 40-75 years with LDL between 70-189 mg/dL (10-year ASCVD risk 7.5-19.9% + risk-enhancing factors)
High-intensity statins
- Atorvastatin: 40-80
- Rosuvastatin: 20-40
Moderate-intensity statins
- Atorvastatin: 10-20
- Rosuvastatin: 5-10
- Simvastatin: 20-40
- Pravastatin: 40-80
- Lovastatin: 40
- Fluvastatin: 40 BID/ 80 XL
- Pitavastatin: 2-4
Low-intensity statins
- Simvastatin: 10
- Pravastatin: 10-20
- Lovastatin: 20
- Fluvastatin: 20-40
- Pitavastatin: 1
Statin equivalent doses
Pharmacists Rock At Saving Lives and Preventing Fatty deposits
- Pitavastatin 2 mg
- Rosuvastatin 5 mg
- Atorvastatin 10 mg
- Simvastatin 20 mg
- Lovastatin 40 mg
- Pravastatin 40 mg
- Fluvastatin 80 mg
Muscle damage from statins
Symmetrical:
* Occurs within 6 weeks of starting Tx.
Myalgias:
* Muscle soreness and tenderness
Myopathy:
* Muscle weakness +/- CPK elevations
Myositis:
* Muscle inflammation
Rhabdomyolysis:
* Very high CPK (>10,000) + muscle protein in the urine which can lead to acute renal failure
Reducing risk and Managing myalgias
Reducing risk:
* Avoid DDIs
* Don’t use Simvastatin 80 mg/day
* Don’t use Gemfibrozil+statin
Management:
1. Hold statin, check CPK, investigate
- After 2-4 weeks: re-challenge with same statin at same dose or lower dose
- If myalgias return, discontinue statin. Once muscle symptoms resolve, use a low dose of a different statin; gradually increase dose
Statins (brand/generic)
- Atorvastatin (Lipitor)
- Lovastatin (Altoprev): evening meal
- Pravastatin (Pravachol)
- Rosuvastatin (Crestor)
- Simvastatin (Zocor): evening
Statins CIs
- Pregnancy, breastfeeding
- CYP3A4 Inhibitors with simvastatin and lovastatin
- Liver disease
Statins warnings
Muscle damage:
* Myopathy/Rhabdomyolysis with increased CPK +/- acute renal failure
- Higher risk with higher dose, advanced age(>=65 years), niacin, gemfibrozil, CYP3A4 inhibitors
Diabetes:
* Increased A1C/FBG
Statins monitoring, SEs and lipid effect
SEs:
* Myalgia/myopathy
Monitoring:
* Lipid panel 4-12 weeks after starting Tx then every 3-12 months (usually annually)
- Myalgia: check CPK
- Little/no urine: check SCr/BUN
- Abdominal pain or jaundice: check LFTS for hepatotoxicity
Lipid effect: Decrease LDL, increase HDL, decrease TG
Statin DDIs (do not use with simvastatin and lovastatin)
GPACMAN
- Grapefruit
- Protease inhibitors
- Azole antifungals
- Cyclosporine, cobistat
- Macrolides (except Azithromycin)
- Amiodarone
- Non-DHP CCBs
Cyclosporine: Rosuvastatin 5 mg/day
Cobistat: Atorvastatin 20 mg/day
Amiodarone: Simvastatin 20 mg/day or Lovastatin 40 m/day
Non-DHP CCBs: Simvastatin 10 mg/day or Lovastatin 20 mg/day
Non-statin add-on treatment
Ezetimibe (preferred) or PCSK9 inhibitors
- Very high-risk, statin at max dose & LDL remains >= 70 mg/dL
- Primary hypercholesterolemia, statin at max dose & LDL remains >=100 mg/dL
- Hx of multiple ASCVD events or one ASCVD event in a high-risk pt (e.g.,diabetes)
Ezetimibe
MOA: Inhibits absorption of cholesterol in the small intestine
- Zetia
- SEs: myalgias
- Lipid effect: decreases LDL
PCSK9 Inhibitors
MOA: Monoclonal antibodies that block PCSK9 to bind to the LDL receptor
- Alirocumab: HeFH or ASCVD, SC injection
- Evolocumab: HeFH or ASCVD, SC injection
SEs: injection site reactions
Lipid effects: lowers LDL
Bile Acid Sequestrants
MOA: Bind bile acids in the intestine, forming a complex that is excreted in the feces
Colesevelam (Welchol) - with a meal and liquid
* CIs: bowel obstruction
- SEs: constipation, abdominal pain, cramping, bloating, gas, increased TG
- Lipid effects: increases TG
Notes:
* Cholestyramine packet - drink with 2-6 oz water or no -carbonated liquid. It may lead to teeth discoloration, erosion of the enamel or decay
- Colesevelam is an option for pregnant patients
Bile Acid Sequestrants DDIs
Cholestyramine or colestipol:
* Take all other drugs at least 1-4 hrs before or 4-6 hrs after
Colesevelam:
* Take levothyroxine 4 hrs prior
Bile acid sequestrants can decrease the absorption of fat-soluble vitamins (ADEK). Multivitamin may be needed but separate administration
Fibrates
MOA: PPARa activators. ApoC-II increases lipoprotein lipase activity leading to increased catabolism of VLDL particles which decrease TG.
Drugs - Fenofibrate, Fenofibric Acid (Antara, Tricor, Trilipix), Gemfibrozil (Lopid)
- CIs: severe liver disease, including primary biliary cirrhosis. Gallbladder disease
- Warnings: myopathy, increased risk when coadministered with a statin
- SEs: dyspepsia (gemfibrozil), increased LFTs
- Lipid effects: decreased TG (can increase LDL when TG are high)
Fibrates DDIs
- Gemfibrozil should not be given with statins or ezetimibe
- Fibrates can increase the effects of SUs and warfarin
Niacin
MOA: Decreases the rate of hepatic synthesis of VLDL (TG) and LDL. AKA nicotinic acid or vitamin B3
Warnings:
* Rhabdomyolysis, hepatotoxity, increases BG, uric acid
SEs:
* Flushing, pruritus, vomiting, diarrhea, increased BG, hyperuricemia(gout)
Monitoring:
* Check LFTs
- Lipid effects: increases HDL
Notes:
* IR: flushing/itching
- CR/SR: have less flushing but more hepatotoxicity
- ER Niaspan: less flushing and hepatotoxicity
- Take aspirin 325 mg 30-60 min before the dose to reduce flushing (take with food, but avoid spicy food, alcohol and hot beverages)
- Formulations are not interchangeable
- Titrate slowly, take at bedtime with a low-fat snack
Niacin DDIs
- Monitor for other concurrent drugs that are potentially hepatotoxic
- Take niacin 4-6 hrs after bile acid sequestrants
Fish Oils
Adjunct to diet when TG >=500 mg/dL
Drugs - Omega-3 Acid Ethyl Esters (Lovaza), Icosapent ethyl (Vascepa)
- Warnings: hypersensitivity to fish and/or shellfish
- SEs: eructation, dyspepsia, taste perversions
- Lipid effects: decreases TG, can increase LDL with Lovazo
Fish Oil DDIs
- Prolong bleeding time
- Monitor INR if patients are taking warfarin
Lomitapide
- BW: hepatotoxicity
- CIs: active liver disease, pregnancy
