3.2 Drug summary table and Playposit Q

Statins MOA

Inhibit HMG-CoA reductase → ↓ cholesterol synthesis (HMG-CoA Reductase Inhibitors)

Which are the most effective & best-tolerated LDL-lowering drugs?

Atorvastatin

Fluvastatin

Lovastatin

Pitavastatin

Pravastatin

Rosuvastatin

Simvastatin

Are Statins Contraindicated in pregnancy?

YES

Statins monitoring?

Measure liver enzymes (ALT) at baseline; repeat if clinically indicated

Statins ADRs

Myopathy and rhabdomyolysis possible (↑ risk with dose and interacting drugs)

Statins rare ADR

Hepatotoxicity: ~1 case per million person-years

For Statins, myopathy risk increases with?

- age

- renal/hepatic impairment

- CYP inhibitors

Ezetimibe MOA

Inhibits NPC1L1 in small intestine → ↓ cholesterol absorption (Cholesterol Absorption Inhibitor)

Ezetimibe is used as monotherapy in _____________

patients intolerant to statins

Ezetimibe commonly used as

combo with statin or bempedoic acid for an additive LDL reduction

Ezetimibe should be avoided with?

bile acid sequestrants (↓ absorption)

Ezetimibe ADRs

Generally well tolerated; rare rhabdomyolysis (esp. with fibrates)

Is Ezetimibe contraindicated in preganancy?

Yes when used with statins

Bile Acid-Binding Resins MOA

Bind bile acids → ↑ LDL clearance

Bile Acid-Binding Resins include

- Cholestyramine

- Colestipol

- Colesevelam

Cholestyramine / Colestipol ADRs

GI side effects: bloating, dyspepsia, constipation

Bile acid sequestrants are probably the ___________

safest lipid-lowering agents (not absorbed systemically)

Bile Acid Sequestrants are recommended for patients __________

11-20 years old

Bile Acid Sequestrants Drug interactions

Bind many drugs → give other meds 1 h before or 3-4 h after resin

Bile Acid Sequestrants Contraindications

Severe hypertriglyceridemia (↑ TG levels)

Niacin (Nicotinic Acid) effects

↑ HDL-C (most effective), ↓ LDL-C and TGs

Niacin contraindications?

- pregnancy

- peptic ulcer disease

- gout

- concurrent statin use

Niacin ADRs

Flushing, pruritus, dyspepsia

*these cause a ↓ adherence

Niacin can cause _____________

nausea, vomiting, diarrhea

Niacin can cause ________, which is seen by an increase in _____________

- Hepatotoxicity

- serum transaminases (esp. ER form)

Niacin effects on blood sugar?

Causes hyperglycemia and insulin resistance — monitor glucose

Niacin use in diabetics?

check glucose weekly until stable

Fibric Acid Derivatives MOA

Activate PPARα → ↑ lipoprotein lipase activity

Fibric Acid Derivatives include?

- Gemfibrozil

- Fenofibrate

- Ciprofibrate

- Bezafibrate

Fibrates are best for (indications)?

1. chylomicronemia

2. type III hyperlipoproteinemia

3. severe hypertriglyceridemia (>1000 mg/dL)

Fibrates contraindications

pregnancy and children

Fibrates ADRs

GI upset (~5%), myopathy

For Fibrates the FDA withdrew the approval for their use with __________

statins (coadministration ↑ myopathy risk)

Fibrates are relatively contraindicated in ______

renal failure, hepatic dysfunction, gallbladder disease

Omega-3 Fatty Acids (EPA, DHA, Icosapent Ethyl)

↓ TG synthesis, ↑ FA oxidation, ↑ VLDL clearance

Omega-3 is used for _________

severe hypertriglyceridemia (>500-1000 mg/dL)

Icosapent Ethyl (Vascepa) is used ____________

Adjunct to statins for CV event reduction (TG ≥150 mg/dL)

Omega-3 ADRs

- arthralgia

- dyspepsia

- fishy burps

- ↑ LDL, nausea

Omega-3 may ____________, important to monitor with __________

- prolong bleeding time

- anticoagulants

PCSK9 Inhibitors (Alirocumab, Evolocumab) MOA

Monoclonal antibodies inhibit PCSK9 → prevent LDL receptor degradation

PCSK9 Inhibitors Outcome reduction?

- ↓ risk of MI, stroke, and unstable angina

- used in ASCVD, HeFH, HoFH

PCSK9 Inhibitors come as a

Subcutaneous injection every 2-4 weeks

PCSK9 Inhibitors ADRs

- injection reactions

- URTI

- influenza-like symptoms

Evolocumab may _________, while alirocumab can __________

- ↑ diabetes risk (9%)

- ↓ LDL <25 mg/dL

PCSK9 Inhibitors have a _______________

Complementary mechanism to statins (used together)

Inclisiran MOA

siRNA suppresses PCSK9 synthesis → ↓ LDL-C

Inclisiran is used for ______ or _______

HeFH or ASCVD needing more LDL lowering

Inclisiran is used as _______________ (dose & frequency)

Subcutaneous 284 mg at 0, 3 months, then every 6 months

With Inclisiran ____________ are possible

Injection site reactions

Inclisiran causes ___________, which is ____________

- long-lasting PCSK9 suppression

- complementary with statins

Is Inclisiran contraindicated in pregnancy?

YES

Lomitapide MOA

Inhibits microsomal triglyceride transfer protein → ↓ LDL, TC, apoB

Lomitapide is used as ______________

Adjunct for HoFH (↓ LDL 40-50%)

Lomitapide ADRs

GI symptoms, ↑ liver enzymes, hepatic steatosis

Lomitapide is used under _______________

FDA REMS program (risk: hepatotoxicity)

Lomitapide use has to supplemented with?

- Vit E (400 IU)

- linoleic acid (200 mg)

- α-linolenic acid (210 mg)

- EPA (110 mg)

- DHA (80 mg)

Bempedoic Acid MOA

Inhibits ACL → ↓ cholesterol synthesis upstream of HMG-CoA reductase

Bempedoic Acid is used for __________ or _____________

statin-intolerant patients or those not reaching LDL targets

Bempedoic Acid can be used as a combo with?

ezetimibe or statins

Bempedoic Acid ADRs

Mild adverse effects overall

Bempedoic Acid may increase _______, which increases the risk of __________

↑ uric acid levels → risk of gout

Evinacumab-dgnb MOA

Monoclonal antibody inhibiting angiopoietin-like protein 3 (ANGPTL3 Inhibitor)

Evinacumab is used as ____________

Adjunct to lipid-lowering therapy in HoFH

Evinacumab effects on LDL?

↓ LDL-C by ~50%

Evinacumab may cause ____________

severe hypersensitivity reactions

Is Evinacumab contraindicated in pregnancy?

YES

Which of the following statins are primarily metabolized through CYP3A4?

A. Atorvastatin

B. Rosuvastatin

C. Simvastatin

D. Fluvastatin

E. Lovastatin

F. Pravastatin

A. Atorvastatin

C. Simvastatin

E. Lovastatin

What are the appropriate high intensity doses for Rosuvastatin and Atorvastatin?

Rosuvastatin 20-40 mg

Atorvastatin 40-80 mg

What is statin intolerance?

A) When a patient experiences adverse effects and not able to tolerate the associated side effects of statin therapy

B) When a patient says they do not want to take the medication because they do not feel their cholesterol improving

C) When a patient is unable to afford their statin medication

D) When a patient experiences gastrointestinal discomfort that occurs when the body ingests lactose-containing products

A) When a patient experiences adverse effects and not able to tolerate the associated side effects of statin therapy

What would be an appropriate counseling point when discussing PCSK9 inhibitors?

A) Take one pill by mouth once daily to ensure medication compliance

B) This medication should never be at room temperature prior to administration

C) Make sure to stay up to date with routine vaccinations

D) Due to its high cost, they should never be considered as a therapy option

C) Make sure to stay up to date with routine vaccinations

In the absence of ASCVD or associated risk factors, omega-3 fatty acids should generally be recommended when triglyceride levels are greater than ____ mg/dL.

A) 150

B) 300

C) 400

D) 500

D) 500

What is a possible adverse effect of niacin therapy?

A) Flushing

B) Hypouricemia

C) Hypoglycemia

D) Decreased HDL levels

A) Flushing

What is one way to decrease the risk for drug interactions and/or adverse effects with bile acid sequestrants?

A) Use a powder formulation as they are better tolerated

B) Take other medications 1 hour prior or 3-4 hours after

C) Take them with fat-soluble vitamins to help their absorption

D) They are very well tolerated with minimal drug interactions

B) Take other medications 1 hour prior or 3-4 hours after

What agent has a REMS program due to hepatotoxicity?

A) Bempedoic acid

B) Evinacumab

C) Lomitapide

D) Alirocumab

C) Lomitapide