Dyslipidemia Flashcards
What is the Friedewald equation to calculate LDL from TC, HDL, and TG?
LDL = TC - HDL - (TG/5)
cannot use if TG > 400mg/dL
What type of lipoproteins carry triglycerides?
Very-low density lipoproteins carry triglycerides
What is the equation to determine total cholesterol?
TC = LDL + HDL + VLDL + TG
What are drugs that increase LDL and TG? (5 classes)
Protease inhibitors
Atypical antipsychotics
Steroids
Diuretics
Transplant drugs/Immunosuppressants (cyclosporine, tacrolimus)
What drugs increase LDL only (2) and TG only (3)
LDL only
- fibrates
- fish oils (except Vascepa)
TG only
- IV lipid emulsions (propofol)
- clevidipine
- bile acid sequestrants
What are the normal ranges for non-HDL, LDL, HDL (men vs women), TG
non-HDL: <130 is desirable
LDL: <100 is desirable
- ≥190 is very high
HDL:
- >40 in men
- > 50 in women
Triglycerides: <150 is normal
- ≥ 500 is very high
What natural products are not recommended (1) and what are good for patients (4)
- Red Yeast Rice -> NOT recommended
- plant stanols, sterols, fibrous foods -> GOOD!
- OTC fish oils -> GOOD!
- garlic -> meh
Do we want to limit unsaturated or saturated fat?
Limit saturated fat to 5-6% of the diet
What intensity of statin is recommended for:
- Clinical ASCVD
- Elevations of LDL ≥ 190 at any age
- diabetes & age 40-75 years & LDL 70-189 & multiple ASCVD risk factors
- diabetes & age 40-75 years & LDL 70-189 & no ASCVD risk factors
- age 40-75 with LDL 70-189 & ASCVD ≥ 20%
- age 40-75 with LDL 80-189 & ASCVD 7.5-19.9 + risk-enhancing factors
HIGH
- Clinical ASCVD
- LDL ≥ 190 at any age
- diabetes & age 40-75 years & LDL 70-189 & multiple ASCVD risk factors
- age 40-75 with LDL 70-189 & ASCVD ≥ 20%
MODERATE
- diabetes & age 40-75 years & LDL 70-189 & without ASCVD risk factors
- age 40-75 with LDL 80-189 & ASCVD 7.5-19.9 + risk-enhancing factors
What are the moderate intensity statins? (7)
(daily dose decreases LDL ~30-49%)
- atorva 10-20mg
- rosuva 5-10mg
- simva 20-40mg
- prava 40-80mg
- lova 40mg
- fluva 80mg
- pitava 2-4mg
What are the equivalent doses to atorvastatin 10mg? (pitavastatin, rosuva, sima, lova, prava, fluva)
pitava 2mg
rosuva 5mg
atorva 10mg
simva 20mg
lova 40mg
prava 40mg
fluva 80mg
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What is the MOAs of statins? Contraindications (4)? Effect of LDLs, HDLs, and TG?
MOA - inhibit HMG CoA Reductase, which inhibits the rate-limiting step of cholesterol synthesis
Contraindications
- active liver disease
- pregnancy category X
- breastfeeding
- taking concurrent strong 3A4 inhibitors (esp. simvastatin and lovastatin)
Decreases LDL
Increases HDL
Decreases TG
Which statins need to be in the evening?
Simvastatin
Lovastatin
Fluvastatin
(Sam Loathes the Flu)
What are the significant drug interactions with statins from the pneumonic G<3PACMAN? What statins should we avoid with these drug interactions?
Grapefruit
Protease inhibitors
Azole antifungals
Cyclosporin, cobicistat (rosuva 5mg max for cyclosporin, atora 20mg max for cobicistat)
Macrolides
Amiodarone (simva 20mg/day max, lova 40mg/day max)
Non-DHP CCBs (simva 10mg/day max, lova 20mg/day max)
Do not use simvastatin or lovastain with G through M
How do we reduce the risk of myalgias with statins (3)? How do we manage the symptoms of myalgia?
Reduce risk
- Avoid drug interactions
- Do not use simvastatin 80mg/day
- Do not combine gemfibrozil + statin
Manage symptoms
- Hold statin, check CPK
- After 2-4 weeks, rechallenge (use same statin at the same or lower dose)
- IF myalgias return, discontinue the statin. Once symptoms resolve, try a lower dose of a different statin and gradually increase the dose
What is ezetimibe’s MOA?
When do we add this med?
What are 2 warnings?
What medication should we NOT use with ezetimibe due to increased risk of cholelithiasis?
What does it do to LDL, HDL, and TG
MOA - blocks the absorption of cholesterol at brush border of small intestine
Warnings
- Avoid use in hepatic impairment
- Skeletal muscle effects with combined with a statin
DO NOT USE WITH GEMFIBROZIL
Decreases LDL
Increases HDL
Decreases TG
What is the MOA of bile acid sequestrants? What are the contraindications to cholestyramine (1) and colesevelam (3)? Side effects (3)? What do they do to LDL, HDL and TG?
cholestyramine, colesevelam, colestipol
MOA - bind bile acids in the intestine forming a complex that is excreted in the feces
Contraindications:
- cholestyramine: complete biliary obstruction
- colesevelam: bowel obstruction, TG > 500, hx of TG-induced pancreatitis
Side effects:
- conspitation
- abdominal pain/cramping/gas
- increased triglycerides
Decreases LDL
Increases HDL
Increases TG
Which bile acid sequestrant has the least drug interactions and is preferred in pregnancy? How do we separate med administration with the other BASs? Which BAS is also approved for T2DM?
colesevelam has the least drug interactions and is preferred in pregnancy
for cholestyramine or colestipol, separate all drugs by 1-4 hours before or 4-6 hours after the BAS
colesevelam is also approved for glycemic control in T2DM
What is the MOA of fibrates? What are the contraindications (4)? What are 3 side effects?
MOA - activates PPARα, which causes elimination and decreased synthesis of VLDL and TGs and increased HDL
**BUT if TGs are high, it can increase LDL
Contraindications
- severe liver disease
- severe renal disease (CrCl <30)
- gallbladder disease
- nursing mothers
Side effects
- increased LFTs
- myopathy (risk increased w/ statin
- increased SCr
What is the most important drug interaction for gemfibrozil?
Gemfibrozil should not be used with ezetimibe or statins due to increased risk of myopathy and rhabdomyolysis
What is the MOA of niacin? What are 2 dosing notes? What are 3 contraindications? What are 4 warnings? What are 3 side effects
MOA - decreases rate of hepatic synthesis of VLDL and LDL, increases HDL
Dosing
- tirate slowly
- take with food
Contraindications
- active liver disease
- active PUD
- arterial bleeding
Warnings
- rhabdomyolysis
- hepatoxicity
- increased BG
- increased uric acid
Side effects
- flushing (esp. IR form)
- pruritis
- vomiting/diarrhea
How can you reduce the flushing with niacin?
Take with aspirin 325mg about an hour before the dose or take the extended released formulation!
When are fish oils indicated? Which fish oil will not increase LDL?
Indicated as an adjunct to diet in patients with TGs > 500
Vascepa will not increase LDLs like the others
Decreases triglycerides
What is the MOA of PCSK9 inhibitors? When are they indicated?
Alirocumab (Praluent), Evolocumab (Repatha)
MOA - block PCSK9’s ability to degrade LDL receptors, which results in increased LDL clearance and lower LDL
Indicated in patients with established ASCVD or familial hypercholesterolemia
- alirocumab for heterozygous familial hypercholesterolemia
- evolocumab for homozygous or heterozygous
What is the MOA of bempedoic acid?
What is the MOA of inclisiran? When should you NOT use inclisiran?
Bempedoic acid - inhibits cholesterol synthesis by inhibiting adenosine triphosphate-citrate lyase (part of cholesterol synthesis pathway)
Inclisiran - inhibits production of PCSK9, which results in increased LDL receptor activity
- do not use with PCSK9 inhibitor since it would be duplicate mechanisms
