Lipids Flashcards by Marc Duke

What was the result of the “Mr. Fit” trial (ASCHD Mortality and Cholesterol)

Total cholesterol levels have a strong correlation to 10 year coronary heart disease

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How can you tell the extent of CAD risk?

Calcification (CAC score) from a Heart Saver CT

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Describe the overall process of atherosclerotic vessel changes/lesion development.

Infiltration into intima
Worsening build-up develops
Thrombus formation and increased calcification
Vessel rupture –> loosened thrombus
Embolism formed –> MI, CVA, PE

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Describe how Bile Acid Resins (BARs) reduce LDL cholesterol.

BARs bind bile acids released that solubilize fats for absorption
Bile acids can’t be reabsorbed –> pooped out
Liver utilizes serum LDL to form new cholesterol –> ↓ serum level

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↑↓ ≥ ≤

[symbols to copy/paste]

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What are the BAR ADRs?

What % get SE? Why?

1) constipation, flatulence, bloating, epigastric fullness, nausea (not as much with newer)
2) 100% of ppl get SE. Because the SE are dose related and occur with every administration

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How to manage SE of BARs?
What % of people d/c use? Why?
Suggestions to ↓ aversions to powdered formula?

1) Start w/ small doses and titrate up
2) ~40% d/c w/in a year b/c of GI ADRs
3) Suggestions:
- Mix powder with pulpy beverage and serve cold
- Do not mix w/ carbonated beverage (gas + gas)

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What are some warnings associated with BARs?

A lot of Rx interactions (complexation interactions)
Fat soluble vitamins may not get absorbed (A,D,E,K)
Take vitamins/meds 4 hour before BARs

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1) Describe Niacin’s MoA.
2) What is the immediate max dose/day?
3) What is the sustained release max dose/day?

1) ↓ liver production of VLDL –> ↓ LDL because of ↓ precursors
2) 4000 mg/day max for immediate release
3) 2000 mg/day max for sustained release

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1) Which dosage form of Niacin has more common SE? Why?

2) Which of Niacin’s dosage forms is of more concern for serious ADRs? Why?

1) Immediate release; b/c higher max peak concentration
2) Sustained release
- Because longer DoA and larger area under curve = ↑ concentration over time and longer build-up
- –> Hepatotoxicity

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1) What MoA occurs 100% of the time to some extent when taking Niacin? What SE does it cause?
2) Approx onset and duration of this SE?

1) vasodilation of vessels in skin; flushing

2) 15 min onset, 15-30 min duration

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1) What are the common SE of Niacin?
2) What are the serious SE of Niacin?
3) Which serious SE occur only if certain conditions already present?

1) flushing, itching, rash, hives
2) liver toxicity, muscle damage, gastritis/GI bleed (ulceration)
3) Hyperglycemia and DM
- BGL may be harder to control or may ↑ if already ↑
Gout
- Symptoms may be worsened if ↑ uric acid levels already present

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1) How can Niacin SE be prevented/reduced?

2) Which prevention method is not longer recommended? Why?

1) small doses and titrate ↑ (get used to slowly)
- take w/ food (slows absorption)
- XR –> ↓ SE (but concern for liver tox)
- avoid admin w/ hot fluids and EtOH (worsen Sx)
2) 325 mg ASA; not recomm d/t concerns w/ NSAID overuse

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What is the definition of myalgia?

Muscle pain without ↑ in CK-MB

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1) Define potency

2) If a drug is potent, what does that mean?

1) How much of a drug it takes to achieve a desired effect
2) If an extremely small dose of drug “A” –> desired effect versus and a large dose of drug “B” for the same effect, then drug “A” is more potent than “B”.

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1) Cholestyramine lipid average effects:

1) TRG ↑ and LDL-C ↓

- approx. 10-25%

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1) Niacin lipid average effects:

1) TRG ↓ about double of HDL-C ↑ and LDL-C ↓ (15-25%)

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1) Statin lipid effects (Atorvastatin):

1) TRG ↓ good and LDL-C ↓ great

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Summary of Lipid Effects By Drug Class:

1) BARs (Cholestyramine)
2) Niacin
3) Statins
4) Fibric Acids (Gemfibrozil)
5) Omega-3 Fatty Acids (Lovaza)
6) Ezetimibe
7) PCSK9 Inhibitors

1) TRG ↑↑, LDL ↓↓
2) TRG ↓↓, HDL ↑↑, LDL ↓↓
3) TRG ↓↓, LDL ↓↓↓
4) TRG ↓↓↓, HDL ↑↑
5) TRG ↓↓, HDL ↑,
* may ↑↑ LDL in some
6) (solo or combo) LDL ↓↓
7) (solo or combo) LDL ↓↓↓

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1) Fibric Acid lipid effects (Gemfibrozil):

1) TRG ↓ A lot and HDL-C ↑ some

1) Omega-3 FA lipid effects (Lovaza):

1) TRG ↓ A lot and HDL-C ↑ 10%

- can LDL-C ↑ substantially, so check lipids at least once

1) Ezetimibe lipid effects (Zetia):

1) LDL-C ↓ 15-20%

- monothpy or w/ statin

1) PCSK9 Inhibitor lipid effects:

1) LDL-C ↓ 50-60% mono;

LDL-C ↓ 40% w/ statin

Why are statins considered the drug of choice?

“Statin magic”

- ↓ LDL alone more than all other Rx

Common statin ADRs

- GI intol - Myalgia - Flu-like Sx - Fatigue

Statin hepatotoxicity ADR three monitoring key points.

- Watch for >3x upper limit of LFTs on 2 consecutive occasions - Routine LFT monitor no longer req'd b/c serious liver problems are now rare - ↓ dose or D/C until levels = nml then re-challenge

What is the spectrum of statin-induced myopathy and CK levels?

- Small ↑ in CK is nml - > 10x ↑ in CK = myopathy - > 10,000x ↑ in CK = Rhabdo

What factors can ↑ incidence of myopathy with statins?

1) Higher statin doses - r/t [statin] in blood - ↓ incidence w/ ↑ potency 2) Renal impairment 3) Statin + Fibrate 4) Rx interfering w/ Statin metabolism - Macrolide, cyclosporin, -azole's

Management of unexplained severe muscle Sx or fatigue in Statins?

1) D/C Statin 2) Address possible Rhabdo - CK, SCr, UA for myoglobinuria

Management of mild-moderate muscle symptoms in Statins?

1) D/C statin until Sx eval - consider other causes (HoTSH, renal/hepatic, RA, steroid-induced) 2) If >2 mo and Sx not resolved or CK still ↑ = not Statin 3) **Resume Statin if not cause**

1) How is Cognitive impairment different from Dementia? | 2) What is the prognosis if a patient develops cognitive impairments on a Statin?

1) Cognitive impairment involves reduced cognitive functions (processing speed, etc..) while Dementia involves memory-based Sx 2) Risk goes away following D/C, fxn should return to nml after D/C

1) What is the MoA for Fibric Acids? | 2) What is its primary activity?

1) ↑ activity of lipoprotein lipase --> ↑ breakdown of VLDLs and chylomicrons 2) Lowers TRGs

What are the Fibric Acid ADRs?

- Dyspepsia, ABD pain - Myopathy (↑ w/ renal impairment and concurrent statin) - ↑ hypoglycemic effect w/ sulfonylureas

What are the indications for Omega-3 Fatty Acids?

Adjunct to diet to ↓ TRG if severe ( >500)

What are the common ADRs for Omega-3 FAs?

- eructation (burping) - flu-like Sx - dyspepsia - taste sensation changes

What are some warnings to know about Omega-3 FAs?

- Possible hepatic impair - May ↑↑ LDL in some - Seafood allergy - May ↑ bleeding risk on anticoags

Ezetimibe: 1) MoA 2) Indications 3) ADRs

1) Inhibits chol absorption 2) Monothpy or w/ Statin to ↓ LDL 3) No diff from placebo **GASP**

PCSK9 Inhibitors: 1) MoA 2) Route 3) Efficacy 4) Other important notes

1) inhibits enzyme that bkdwn LDL receptors 2) Subcut, can be self-admin 3) Mono ↓ LDL 50-60%; w/ Statin ↓ LDL 40% 4) Puts a price tag on life $$$$ and QAYL; great additive but not proven to ↓ M/M, esp w/ familial HLD

PCSK9 Inhibitor ADRs

- Injection site swelling/rash - Limb/back pain - fatigue, cold/flu-like Sx - Neurocognitive (conf, memory impair, diff focus)

Overall message of "Old Way", ATP 3?

- optimal LDL approx 40 mg/dL | - At this level, showed same risk as ppl w/out LDL issues

Overall message of "New Way", AHA/ACC?

1) HDL : LDL more important - --> No LDL goal 2) ↑ Statin --> ↑ benefits - --> No Statin --> No proven risk reduction in ASCVD

What are the 4 Statin Benefit Groups?

1) Individ w/ ASCVD: ACS + Hx 2) ≥ 21 yo w/ LDL ≥ 190 3) DM, 40-75 yo, LDL 70-189 4) No DM, 40-75, LDL 70-189, ASCVD risk ≥ 7.5%

Statin Therapy Intensity for High, Mod, and Low: - % LDL ↓ - One of the Drugs + Dose

1) High: ↓ LDL by ~50%; Atorvastatin 40-80 mg 2) Moderate: ↓ LDL by 30-50%; Atorvastatin 10-20 mg 3) Low: ↓ LDL by < 30%; Simvastatin 10 mg

When is one of the only instances when Low-Intensity Statin Thpy is indicated?

When SE at High and Moderate levels not tolerated

How does a patient meet Very-High Risk criteria for Secondary Prevention?

2 major ASCVD events or 1 major ASCVD event + 2 High Risk Conditions

What are the major ASCVD events for Secondary Prevention?

1) ACS w/in past 12 mo 2) Hx of MI, CVA 3) Hx/Sx of PAD - ABI < 0.85 w/ claudication - prev revascularization - arthroplasty - amputation

What are the Very High RIsk Conditions for Secondary Prevention?

1) ≥ 65 yo 2) HLD family Hx 3) Hx of PCI 4) DM 5) HTN 6) CKD 7) Current smoking 8) Persistent LDL ≥ 100 despite Statin and ezetimibe 8) Hx of CHF

What to do if goals not met?

1) eval adherence to statin thpy and efforts at lifestyle changes 2) ↑ statin dose if possible 3) Add ezetimibe and/or PCSK9 4) Address other risk factors - Tobacco, DM, HTN