Hyperlipidemia

Question 1

Bile Acid Sequestrants (3 drugs)

Answer 1

• Cholestyramine
• Colesevalam
• Colestipol
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Question 2

HMG CoA Reductace Inhibitors (4 drugs)

Answer 2

(statins)

• Lovastatin
• Simvastatin
• Atorvastatin
• Rosuvastatin

Question 3

Fibrates (3 drugs)

Answer 3

• Gemfibrozil
• Fenofibrate
• Clofibrate

Question 4

Cholesterol Absorption Inhibitors (1 drug)

Answer 4

• Ezetimibe

Question 5

Bile Acid Sequestrants

• Drugs:
• Uses:
• MOA:
• Effectiveness:
• Dosing:
• ADRs:
• Contraindications:
• Monitoring:

Answer 5

• Drugs: cholestryramine [TQ], colesevalam, colestipol
• Uses: reduce major coronary events, reduce CHD mortality, decrease itching associated with cholestasis
• MOA: increase LDL catabolism
• Effectiveness:
  
  • Lowers LDL and TC 15-25%
  • Raises VLDL
  • NO effect on HDL
• Dosing: give 1 hour before or 4-6 hours after meds
• ADRs: GI distress, constipation, decreased absorption of drugs, vitamin K and folate affected
• Contraindications: dysbetalipoproteinemia, raised TG (especially >400mg/dL) [TQ]
• Slow titration and/or increased intake of fiber may decrease ADRs

Question 6

Niacin

• Drugs:
• Uses:
• MOA:
• Effectiveness:
• Dosing:
• ADRs:
• Monitoring:

Answer 6

• Nicotinic acid (NOT nicotinamide)
• Uses: reduces major coronary events and mortality
• MOA: decreases LDL and VLDL synthesis
• Effectiveness:
  
  • Lowers LDL 15-25%
  • Lowers TG 30-40%
  • Raises HDL 15-35% [TQ]
• Dosing: slowly increase dose, administer with aspirin or NSAIDs to offset vasodilatory effects
• ADRs: flushing/headache (prostaglandin-mediated vasodilation) [TQ], hyperglycemia, hyperuricemia, GI distress, hepatotoxicity
• Monitoring: monitor uric acid, LFT and blood glucose

Question 7

HMG CoA Reductase Inhibitors

• Drugs:
• Uses:
• MOA:
• Effectiveness:
• Dosing:
• ADRs:
• Contraindications:
• Monitoring:
• Other:

Answer 7

• Drugs: lovastatin, simvastatin, atovarstatin, rosuvastatin
• Uses: reduce coronary events and procedures, reduce CHD mortality, reduce stroke, reduce total mortality
• MOA: increases LDL catabolism [TQ]
• Effectiveness:
  
  • Lowers TC and TG 15-20%
  • Raises HDL 5-15%
  • Lowers LDL (dose dependent)
• Dosing: absorbed with food, LDL lowering is dependent on dose
• ADRs: GI, rash, headache, muscle pain (must check CPK) [TQ], increased LFTs
• Contraindications: avoid erythromycin, niacin and gemfibrozil, monitor PT with warfarin, digoxin concentrations increased, avoid grapefruit juice
• Monitoring: monitor LFTs 6-12 weeks [TQ], monitor creatinine kinase
• TG reduction is dependent predominantly on treatment of baseline TGs, discontinue if liver enzymes >3x upper limit

Question 8

Lovastatin

Answer 8

• HMG CoA Reductase Inhibitor
• Prodrug
• Recommended starting dose to lower cholesterol 20%
• Must be taken at night
• Patients on immunosuppressants need to adjust
• Avoid combo with fibrates and other statins

Question 9

Simvastatin

Answer 9

• HMG CoA Reductase Inhibitor
• Prodrug
• Must be taken at night
• ADRs: severe renal insufficiency
• Interacts with cyclosporine, niacin and fibrates

Question 10

Atorvastatin

Answer 10

• HMG CoA Reductase Inhibitor
• Active as given, not a prodrug
• Used for renal patients (?)
• Adjust doses every 4 weeks
  
  • Not required in renal impairment
• Avoid with active liver disease, check liver status [TQ]

Question 11

Rosuvastatin

Answer 11

• HMG CoA Reductase Inhibitor
• Adjust doses every 4 weeks
• Avoid in liver impairment

Question 12

Fibrates

• Drugs:
• Uses:
• MOA:
• Effectiveness:
• Dosing:
• ADRs:
• Contraindications:
• Other:

Answer 12

• Gemfibrozil, Fenofibrate, Clofibrate
• Reduce coronary lesions and coronary events
• MOA: increase VLDL clearance and decrease VLDL synthesis
• Effectiveness:
  
  • Lowers TGs 20-50%
  • Lowers TC
  • Lowers VLDL
  • Lowers LDL 5-20%
  • Raises HDL 10-20%
• Dosing: give before morning/evening meals (to prevent GI probs)
• ADRs: GI, myalgias, rash, increased risk of gallstone formation due to increased cholesterol concentrations in bile [TQ]
• Contraindications: avoid with lovastatin and use caution with other statins
• Fenofibrate is a uricosuric agent in the treatment of gout

Question 13

Cholesterol Absorption Inhibitors

• Drugs:
• Uses:
• MOA:
• Effectiveness:
• Dosing:
• ADRs:
• Contraindications:

Answer 13

• Ezetimibe
• Uses: reduces TC, LDL, and Apo-B in primary hypercholesterolemia, can treat famililial hypercholesterolemia
• MOA: inhibits absorption of cholesterol at brush border of SI via the sterol transporter NPC1L1 [TQ], active metabolite
• Effectiveness:
  
  • Liver: decreases delivery of cholesterol, reduces cholesterol stones
  • Blood: increases clearance of cholesterol
• Dosing: adjunctive to therapy to diet, can combine with a statin
• ADRs: abdominal pain, anaphylaxis, angioedema, cholelithiasis
• Contraindications: statins if active liver disease, may increase cyclosporine concentration

Question 14

Red Yeast Rice

Answer 14

• Yeast forms monocolons that inhibit HMG-CoA reductase
• Varies in potency

Question 15

Probucol

Answer 15

• Treatment of high cholesterol with only a modest effect on LDL
• Not proven to reduce CHD risks
• Prolongs QT interval

Question 16

Folate and Vitamin B₁₂

Answer 16

• Treat patients with increased homocysteine concentrations

Question 17

Estrogens

Answer 17

• Increase HDL by increasing Apo-A production and by inhibiting hepatic lipase activity
• Does reduce LDL but should NOT be used instead of lipid lowering therapy (adjunct only)

Question 18

Omega 3 Acid Ethyl Esters

• Drugs:
• Uses:
• MOA:
• Dosing:
• Contraindications:

Answer 18

• Drugs: Fish oil, Lovaza (from fish), Vascepa (icasapent ethyl ester)
• Uses: for patients with TG > 500mg/dL, adjunctive to diet
• MOA: decrease synthesis of VLDL and increase clearance of TG from VLDL, increase LPL
• Dosing: take with food, do NOT crush
• Contraindications: shellfish allergy [TQ], A fib (lovaza), monitor LFTs (vascepa)

Question 19

Major atherogenic lipoprotein

Answer 19

Low Density Lipoprotein (LDL)

Question 20

Elevations in _____ are associated with increased risk in patients with metabolic syndrome

Answer 20

Triglycerides

Question 21

A cholesterol-rich lipoprotein that transports cholesterol from tissues to the liver

Answer 21

High Density Lipoprotein

(High concentrations lower CDH risk)

Question 22

Proteins on the surface of lipoproteins that regulate metabolism of lipoproteins and are important to cellular uptake

Answer 22

Apolipoproteins

Question 23

HMG-CoA is AKA

Answer 23

3-Hydroxy-3-Methylglutaryl-Coenzyme A

Question 24

What is the Adult Treatment Panel III?

Answer 24

• Guidelines from National Cholesterol Education Program (NCEP)
• Management of hyperlipidemia in adults
• Recommends early identification of risk, then lifestyle modification, and then medication

Question 25

Risk Factors for Primary Dyslipidemia

Answer 25

* Modifiable (HD-PODS) * HTN * Obesity * Smoking * Physical inactivity * Diabetes * Drugs * Non-Modifiable (FAG.. you can't change them to be straight) * Age * Gender * Family history

Question 26

Risk Factors for Secondary Dyslipidemia

Answer 26

* Diabetes * Hypothyroidism * Obstructive liver disease * Chronic renal failure * Drugs that rase LDL and lower HDL

Question 27

Drugs that Affect Lipids

Answer 27

* Beta Blockers * Anabolic Steroids * Progestational Agents * Corticosteroids * Protease Inhibitors for HIV * Estrogens * Thiazide Diuretics * Antipsychotics (Olanzepine and Clozapine) (BEAT C-PAP)

Question 28

Diagnosis

Answer 28

* Fasting lipid panel every 5 years after age 20 * LDL * HDL * TG * NCEP: states there should be more frequent measurements in those with multiple risk factors

Question 29

Optimal LDL:

Answer 29

\<100

Question 30

* Low HDL: * High HDL:

Answer 30

* Low: \<40 (bad) * High: \>60 (good)

Question 31

Optimal TC

Answer 31

\<200

Question 32

What does the ATP III state about LDL goals for risk categories?

Answer 32

As the risks get higher, the LDL goal gets lower. ``` Low risk: LDL goal is \<160mg/dl High risk (CHD): LDL goal is \<100mg/dl ```

Question 33

NCEP Guidelines

Answer 33

* _Primary focus of therapy: LDL [TQ]_ * Treat elevated TGs with intensified weight management and increased physical activity * If TGs remain \>200mg/dl after LDL goal is reached, secondary goal: non-HDL cholesterol of 30mg/dl high than LDL goal * Non-HDL = TC - HDL

Question 34

ATP III First Steps: Non-Pharmacologic Therapy Recommendations * Saturated Fat: * Cholesterol: * Plant Stanols, Sterols: * Fiber * Total Calories * Physical Activity

Answer 34

* Saturated Fat: \<7% of total calories * Cholesterol: \<200mg/day * Plant Stanols, Sterols: 2gm/day * Fiber: 10-25gm/day * Total Calories: adjust to maintain desirable weight * Physical Activity: ~200kcal/day

Question 35

Weight and HDLs

Answer 35

* Inverse correlation between body weight and HDL * For every 3kg (7lb) of weight loss, HDL increases 1mg/dl

Question 36

Smoking and HDLs

Answer 36

* Smokers have 15-20% lower HDLs * Cessation increases HDLs * Levels return to normal within 30-60 days * HDL may increase 12mg/dl in 60 days * If patients return to smoking, HDL decreases to baseline * 2 in 5 smoking deaths are from CV disease * 1 in 5 deaths from CV disease is due to smoke * Risk of dying following an MI is 40% greater for smokers

Question 37

Exercise and HDLs

Answer 37

* Increasess HDL in a dose dependent manner * Encourage exercise

Question 38

ATP Recommendation Drug Therapy for Primary Prevention First Step:

Answer 38

* Initiate LDL-lowering drug (after 3 months lifestyle therapies) * Options: statins, bile acid sequestrant, nicotinic acid * Continue therapeutic lifestyle changes as well * Return in 6 weeks

Question 39

ATP Recommendation Drug Therapy for Primary Prevention Second Step:

Answer 39

* Intensify LDL-lowering therapy (if goal isn't achieved) * Options: higher statins, statin + bile acid sequestrant, statin + nicotinic acid * Return in 6 weeks

Question 40

ATP Recommendation Drug Therapy for Primary Prevention Third Step:

Answer 40

* Indensify LDL therapy or refer to lipid specialist (if goal still isn't met) * Treat other lipid risk factors: * High TGs (\>200mg/dl) * Low HDL (\<40mg/dl) * Monitor response and adherance every 4-6 months

Question 41

ATP Recommendation Drug Therapy for Secondary Prevention For CHD and CHD Risk Equivalents

Answer 41

LDL goal: \<100mg/dl * First: achivel LDL goal * Second: modify other lipid and non-lipid risk factors * Patients hospitalized for coronary events: * Measure LDL within 24 hours * Discharge on LDL-lowering drug if \>130mg/dl * Consider LDL-lowering drug if 100-129mg/dl * Start lifestyle therapies as well

Question 42

Determining LDL Goal

Answer 42

* If any of the following: * CAD * PVD * Abdominal aortic aneurysm * Symptomatic carotid disease * DM * Then: LDL should be \<100mg/dl and medication should be started at \>130mg/dl * If none of the above risks, count these factors: * HTN * Smoker * HDL \<40mg/dl * Age (40 in men, 55 in women) * Family history (55 in male relative, 65 in female)

Question 43

Treatment Gap Causes:

Answer 43

* Inadequate dose titration of existing treatment * Patient compliance * Lack of routine follow-up * Limited access to healthcare

Question 44

Improving Adherence

Answer 44

* Simplify med regimens * Provide explicit patient instructions * Encourage use of prompts to help patients to remember * Use systems to reinfore adherence and maintain contact with the patient * Encourage family/friends to support * Reinforce and reward adherence * Increase visits for patients unable to achieve goals * Increase convenience and access to care * Involve patients