Dyslipidemia Flashcards

1
Q

Drugs/conditions that raise LDL and TG

A
  • Diuretics
  • Efavirenz
  • Steroids
  • Immunosuppressants (cyclosporine, tacrolimus)
  • Atypical antipsychotics (aripiprazole, quetiapine, olanzapine, risperidone)
  • Protease inhibitors
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2
Q

Drugs that raise LDL only

A

Fish oils (except Vascepa)

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3
Q

Drugs that raise TG only

A
  • IV lipid emulsions
  • Propofol
  • Bile acid sequestrants
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4
Q

Conditions that raise LDL and TG

A
  • Obesity, poor diet, hypothyroidism, alcoholism, smoking, diabetes, renal/liver disease, nephrotic syndrome
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5
Q

Classification of cholesterol and TG levels

A
  • 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

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6
Q

Friedewald equation

A

LDL = TC - HDL - TG/5

**This formula is not used when the TGs are > 400 mg/dL

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7
Q

What factors included to calculate ASVD risk within the next 10 years?

A

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

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8
Q

Which drugs should not be used if the AST or ALT is >3 times upper limit of normal?

A
  • Niacin
  • Fibrates
  • Potentially statins
  • Ezetimibe
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9
Q

What is the rate limiting step in cholesterol synthesis and what does statins do?

A
  • Statins inhibit the HMG-CoA reductase which prevents it to convert into mevalonate. This is the rate limiting step.
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10
Q

Which patient population needs high intensity statin?

A
  • 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%)
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11
Q

Which patient population needs moderate intensity statin?

A
  • 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)
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12
Q

High-intensity statins

A
  • Atorvastatin: 40-80
  • Rosuvastatin: 20-40
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13
Q

Moderate-intensity statins

A
  • Atorvastatin: 10-20
  • Rosuvastatin: 5-10
  • Simvastatin: 20-40
  • Pravastatin: 40-80
  • Lovastatin: 40
  • Fluvastatin: 40 BID/ 80 XL
  • Pitavastatin: 2-4
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14
Q

Low-intensity statins

A
  • Simvastatin: 10
  • Pravastatin: 10-20
  • Lovastatin: 20
  • Fluvastatin: 20-40
  • Pitavastatin: 1
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15
Q

Statin equivalent doses

A

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
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16
Q

Muscle damage from statins

A

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

17
Q

Reducing risk and Managing myalgias

A

Reducing risk:
* Avoid DDIs
* Don’t use Simvastatin 80 mg/day
* Don’t use Gemfibrozil+statin

Management:
1. Hold statin, check CPK, investigate

  1. After 2-4 weeks: re-challenge with same statin at same dose or lower dose
  2. If myalgias return, discontinue statin. Once muscle symptoms resolve, use a low dose of a different statin; gradually increase dose
18
Q

Statins (brand/generic)

A
  • Atorvastatin (Lipitor)
  • Lovastatin (Altoprev): evening meal
  • Pravastatin (Pravachol)
  • Rosuvastatin (Crestor)
  • Simvastatin (Zocor): evening
19
Q

Statins CIs

A
  • Pregnancy, breastfeeding
  • CYP3A4 Inhibitors with simvastatin and lovastatin
  • Liver disease
20
Q

Statins warnings

A

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

21
Q

Statins monitoring, SEs and lipid effect

A

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

22
Q

Statin DDIs (do not use with simvastatin and lovastatin)

A

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

23
Q

Non-statin add-on treatment

A

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)
24
Q

Ezetimibe

A

MOA: Inhibits absorption of cholesterol in the small intestine

  • Zetia
  • SEs: myalgias
  • Lipid effect: decreases LDL
25
Q

PCSK9 Inhibitors

A

MOA: Monoclonal antibodies that block PCSK9 to bind to the LDL receptor

  1. Alirocumab: HeFH or ASCVD, SC injection
  2. Evolocumab: HeFH or ASCVD, SC injection

SEs: injection site reactions
Lipid effects: lowers LDL

26
Q

Bile Acid Sequestrants

A

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
27
Q

Bile Acid Sequestrants DDIs

A

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

28
Q

Fibrates

A

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)
29
Q

Fibrates DDIs

A
  • Gemfibrozil should not be given with statins or ezetimibe
  • Fibrates can increase the effects of SUs and warfarin
30
Q

Niacin

A

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
31
Q

Niacin DDIs

A
  • Monitor for other concurrent drugs that are potentially hepatotoxic
  • Take niacin 4-6 hrs after bile acid sequestrants
32
Q

Fish Oils

A

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
33
Q

Fish Oil DDIs

A
  • Prolong bleeding time
  • Monitor INR if patients are taking warfarin
34
Q

Lomitapide

A
  • BW: hepatotoxicity
  • CIs: active liver disease, pregnancy