Dyslipidemia Flashcards
Triglycerides > _____ can cause pancreatitis
500
How to calculate non-HDL cholesterol
Non-HDL = Total - HDL
How to calculate LDL cholesterol and when should this equation not be used
LDL = TC - HDL - TG/5
Do NOT use this if TG > 400
What drugs can increase LDL and TG?
Diuretics, efavirenz, steroids, immunosuppressants, atypical antipsychotics, protease inhibitors, retinoids
What drugs can increase LDL
Fish oils (except Vacepa), anabolic steroids, fibrates, progestins, STLG2 inhibitors
What drugs can increase TG
IV lipid emulsions, propofol, bile acid sequestrants (~5%), estrogen, tamoxifen, clevidipine, beta-blockers
Goal levels for Non-HDL, LDL, HDL, TG
Non-HDL: <130
LDL: <100 (>190 is very high)
HDL: >40 (men) >50 (women)
TG: <150 (>500 is very high)
What lipid test can be falsely elevated if the patient did not fast?
TG
Can cause incorrect LDL calculation
What does ASCVD risk calculation estimate? What is the cutoff for a low score?
Risk of having a first CV event in the next 10 years
<7.5% is low
A coronary artery calcium score of ____ indicated a statin should be initiated
> 100
What 3 patient populations should always have a statin initiated
Clinical ASCVD
Diabetes
LDL > 190
OTC fish oils can reduce ____ but raise ____
lower TG
Increase LDL
Statins are the drug of choice in treating what?
High non-HDL and LDL
What are second line therapies if statins cannot be used?
ezetimibe and PCSK9 inhibitors
What are the statin benefit groups?
Clinical ASCVD - High intensity
LDL >190 - High intensity
Diabetes and 40-75 with LDL 70-189 - moderate/high
40-75 with LDL 70-189 - moderate (ASCVD risk 7.5-19.9%) or high (ASCVD risk >20%)
Which cholesterol lowering medications should not be used if AST/ALT are >3 times ULN?
niacin, fibrates, statins and ezetimibe
Statin MOA
inhibit HMG-CoA reductase, preventing conversion of HMG-CoA to mevalonate (rate limiting step for cholesterol synthesis)
What are the moderate intensity statin doses?
Pharmacists Rock AT Saving Lives and PReventing Fatty-deposits
Pitava 2 Rosuva 5 Atorva 10 Simva 20 Lova 40 Prava 40 Fluva 80
When can you see muscle pain from statins?
Any time but usually within 6 weeks
Myalgias vs myopathy vs myositis vs rhabdo?
Myalgias: soreness and tenderness
Myopathy: weakness +/- CPK elevations
Myositis: inflammation
Rhabdo: CPK >10,000 + muscle protein in the urine (myoglobinuria) which can lead to acute renal failure
What simvastatin dose is associated with myalgias?
Simva 80mg/d
What cholesterol lowering medication interacts with statins and causes myalgias?
Gemfibrozil
Statin contrindications
Pregancy
Use with strong CYP3A4 inhibitors (simva and lova)
Liver disease
What factors increase risk of myopathy with statins?
higher dose, advanced age (>65), niacin, CYP3A4 inhibitors, hypothyroidism (uncontrolled), renal impairment
When to check lipid panel after starting statin
4-12 weeks then every 3-12 months
What statins MUST be taken at night?
Lovastatin, fluvastatin and simvastatin
What statins have less drug interactions than other statins?
Rosuva and prava
Significant drug interactions with statins
G-PACMAN Grapefruit Protease inhibitors Azole antifungals Cyclosporine/cobicistat Macrolides (except azithromycin) Amiodarone Non-DHP CCBs
What should you add on if a patient is on a statin max dose and their LDL is still > 70?
Ezetimibe (preferred) or PCSK9 inhibitor
What should you add on if a patient is on a statin max dose and has primary hypercholesterolemia (LDL >190) and their LDL remains >100?
Ezetimibe (preferred) or PCSK9 inhibitor
What do fish oils and fibrates target?
high TG
Ezetimibe drug interactions
Cyclosporine: increases concentration of both statin and cyclosporine
Bile acid sequestrants: decrease ezetimibe concentration, separate 2 hours before or 4 hours after bile acid sequestrants
Increased risk of gallstones with fenofibrate and gemfibrozil (do NOT use with gemfibrozil)
Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) inhibitors MOA
LDL receptors clear the circulating LDL
PCSK9 enzyme increases LDL receptor degredation
PCSK9 inhibitors prevent the degradation of LDL receptors resulting in dramatic reduction in LDL (60%)
PCSK9 inhibitor medications and biggest downfall
Alirocumab (Praluent)
Evolocumab (Repatha)
EXPENSIVE (~$14,000 per year)
How are PCKS9 inhibitors administered and what are the most common side effects?
SQ every 2 weeks or monthly
SE: injection site reactions
Bile acid sequestrant/binding resins MOA
binds to bile acid and forms a complex that is not reabsorbed by enterohepatic circulation and is excreted in the feces
What drugs are bile acid sequestrants/binding resins?
Cholestyramine
Colesevelam (Welchol)
Colestipol
Contraindications for bile acid binding resins
Cholestyramine: biliary obstruction
Colesevelam: bowel obstruction, TG > 500, hx of hypertriglyceridemia induced pancreatitis
Bile acid binding resin side effects and clinical pearls
SE: constipation, abdominal pain, cramping, bloating, gas, INCREASED TG
Not recommended if TG > 300
Colesevelam can be used in pregnancy
Bile acid sequestrant drug interactions
Colesevelam - fewest drug interactions
For cholestyramine or colestipol - take all other drugs 1-4 hours before or 4-6 hours after
Warfarin: can affect INR
Decrease absorption of fat soluble vitamins (ADEK), folate, and iron
Fibrates MOA
peroxisome proliferator receptor apha activators which upregulate expression of apolipoprotein C2 and A1. ApoC-II increases lipoprotein lipase activity leading to catabolism fo VLDL particles (decreases TG)
Fibrate contraindications
severe liver disease
CrCl <30
Gallbladder disease
concurrent use of repaglinide or simvastatin (gemfibrozil only)
Fibrate warnings, SE
Myopathy (esp when given with statin), cholelithiasis, reversible increase in SCr
SE: dyspepsia (gemfibrozil), increased LFTs, increased LDL when TG are high
What medications are fibrates?
fenofibrate, gemfibrozil
Fibrate drug interactions
Gemfibrozil should not be given with ezetimibe or statins - myopathy and rhabdo
Colchicine - increase risk of myopathy
Repaglinide - contraindicated d/t hypoglycemic effects
Sulfonylureas and warfarin - increased effects when administered with fibrates
Niacin contrindications
Active liver disease
PUD o arterial bleeding
Niacin Warnings SE, clinical pearls
Warnings: rhabdo, hepatotoxicity, increased BG, increased uric acid
SE: flushing, pruritus, vomiting, diarrhea, increased BG, hyperuricemia
IR niacin - flushing/itching
CR/SR - more hepatotoxicity
How to reduce flushing/itching with niacin
ASA 325 mg (or ibuprofen 200mg) 30-60 minutes before the dose
With food
Avoid spicy food, alcohol, and hot beverages
When are fish oils indicated?
in addition to diet changes when TG > 500
Lomitapide MOA and indication
decreases apoB by binding to and inhibiting microsomal triglyceride transfer protein
Indication: homozygous familial hypercholesterolemia
Bempedoic acid MOA adn indication
inhibits cholesterol synthesis by inhibiting adenosine triphosphate-citrate lyase (ACL)
Indication: heterozygous familial hypercholesterolemia and in ASCVD requiring additional LDL lowering
Lomitapide boxed warning and contraindications
BBW: hepatotoxicity
Contraindication: active liver disease, pregnancy
