Module 4: Unit B Lipid

Question 1

What are examples of Statins (HMG-CoA Reductase Inhibitors) and what is their MOA?

Answer 1

-STATIN
lovastatin
atorvastatin
Fluvastatin (lescol)
Simvastatin

MOA: Inhibits HMG-CoA reductase, ultimately leading to ↑ LDL receptors in the liver which ↓ LDL (mildly lowers triglycerides and increases HDL)

Question 2

What side effects are associated with statins (HMG-CoA Reductase Inhibitors)?

Answer 2

Hepatotoxicity
Cataracts
New onset dm (elevated A1C and FBG)
Myopathy/rhab

Question 3

What are the indications for statins (HMG-CoA Reductase Inhibitors)?

Answer 3

hypercholesterolemia,
1° & 2° prevention of CV events,
1° prevention of CV events for pts. w/ normal LDL and no ASCVD but + for other CV risk factors, 
post-MI therapy, 
slowing the progression of CAD, 
prevention of MI/stroke in DM

Question 4

What do CYP3A4 inhibitors (grapefruit juice, macrolides, azole antifungals) do to lovastatin, simvastatin, and atorvastatin levels?

Which statins are not affected?

Answer 4

Raise serum levels.

Pravastatin, rosuvastatin, and fluvastatin

Question 5

When can we NOT use statins (HMG-CoA Reductase Inhibitors)?

Answer 5

Pregnancy
Lactation
Active liver disease
Unexplained elevated ALT/AST
Unexplained severe muscle symptoms/ fatigue

Question 6

What are risks with Myopathy/rhabdomyolysis with statins? How should we respond if a patient experiences it? Which Statin has the lowest risk?

Answer 6

Can injure muscle tissue. May progress to myositis (rarely) and rhabdomyolysis (very rare)

If patients experience muscle pain/fatigue, discontinue immediately and test creatinine and urinalysis for myoglobinuria. Can resume statin if rhabdo is ruled out.

Question 7

When should statins (HMG-CoA Reductase Inhibitors) be used cautiously?

Answer 7

Excess alcohol, use of cyp3a4 inhibitor (clari/eryth-romycin), increased risk of rhabdo and muscle injury (renal impairment, uncontrolled hypothyroidism, myopathic drugs (colchicine)), vitamin d and coenzyme deficiency, >65 y/o/

Question 8

What condition can statins (HMG-CoA Reductase Inhibitors) cause?

Answer 8

New-onset DM: many pts. in studies had prediabetes.

Question 9

What are examples of PCSK9 Inhibitors and what is their MOA?

Answer 9

-CUMAB
alirocumab (Praluent)

evolocumab (Repatha)

MOA: Inhibit PCSK9 lead to ↑ availability of LDL receptor sites and ↓ circulating LDL

Question 10

Indication of PCSK9 (alirocumab (Praluent) and evolocumab (Repatha))

Answer 10

Hypercholesterolemia-however statins are the gold standard

Question 11

Why don’t we use PCSK9 Inhibitors more often?

Answer 11

Unclear data about effectiveness at lowering cvd/mortality and very expensive.

Statins are still the gold standard

Question 12

What adverse effects are associated with alirocumab (Praluent) and evolocumab (Repatha) [PCSK9 Inhibitors]?

How is it administered?

Answer 12

Hypersensitivity, Immunogenicity (body aches, flu-like symptoms, and back pain), injection site pain.

Given sub-Q

Question 13

What are examples of Bile acid sequestrants and what is their MOA?

Answer 13

colesevelam (Welchol)

MOA: Prevents reabsorption of bile acids and promotes excretion, ultimately leading to ↑ LDL receptors

Question 14

Indication for Bile acid sequestrants: colesevelam (Welchol)

Answer 14

Adjunct to statins in the treatment of hypercholesterolemia

Question 15

What patient education is important to review with Bile acid sequestrants (colesevelam [Welchol])?

Answer 15

Bile acid resins blocks reabsorption from food, they must be taken during meals.

Can bind (prevent absorption) with thiazide diuretics, digoxin, warfarin, and others, so give PO meds 1 hour before or 4 hours after sequestrants. Vitamins 4 hours before!

Recommend ↑ fiber and fluid intake

Question 16

What side effects are associated with Bile acid sequestrants (Welchol)?

Answer 16

Local GI effects only: constipation, bloating, indigestion.

Question 17

What are contraindications to Bile acid sequestrants (Welchol)? Cautions?

Answer 17

Contraindication: history of bowel obstruction, triglycerides >500, hx of hypertriglyceridemia-induced pancreatitis.

Caution: gastroparesis, GI motility disorders, hx major GI sx. Fat soluble deficiency (may decrease absorption of)

Question 18

What are examples of Fibric acid derivatives and what is their MOA?

Answer 18

(FIB)
gemfibrozil (Lopid)
fenofibrate (Tricor)

MOA: ↓ triglycerides by reducing VLDL levels and can ↑ HDL.

Question 19

indications for gemfibrozil (Lopid) and fenofibrate (Tricor)

Answer 19

-FIBR-
hypertriglyceridemia

Third-line for lipid-lowering; best for triglycerides after weight loss and dietary interventions fail

Question 20

What patients should not receive Fibric acid derivatives (Lopid & Tricor)?

Answer 20

Patients with liver or gallbladder disease.

↑ risk of gallstones 2° to ↑ biliary cholesterol

liver toxicity-monitor LFT as ↑ risk of liver CA

Question 21

What adverse effects are associated with Fibric acid derivatives (Lopid) & Tricor)? Drug to drug?

Answer 21

May cause myopathy,rhabdomyolysis, and hemoglobin abnormalities.

Displaces warfarin from albumin, which ↑ anticoagulation and bleeding risk

Question 22

.

Answer 22

.

Question 23

Example of Cholesterol absorption inhibitors?

Answer 23

Ezetimibe (Zetia)

Question 24

Indication for Cholesterol absorption inhibitors [Ezetimibe (Zetia)]?

Answer 24

Adjunct to lifestyle interventions and/or statin for hypercholesterolemia.

Monotherapy for patients who can’t tolerate statins

Note: Cardiaovasular events are not reduced

Question 25

MOA of Cholesterol absorption inhibitors [Ezetimibe (Zetia)]?

Answer 25

Inhibits absorption of dietary cholesterol in the brush border of the small intestine=reduced hepatic cholesterol stored and increased blood clearance.

Question 26

Safety, D2D, etc. with Ezetimibe (Zetia)

Answer 26

• Avoid use in patients with hepatic insufficiency
• Minimal SE compared to placebo in clinical trials.
• Postmarketing reports of (rare) myopathy, rhabdo, hepatitis, pancreatitis, and thrombocytopenia
• Statins: may increase the risk of hepatotoxicity and myopathy
• fibrates: may increase the risk of gallstones and myopathy
• sequestrants: absorption may be decreased because of insoluble bond in the GI tract
• cyclosporine: may increase levels

Question 27

Indication for Niacin?

Answer 27

It is no longer recommended in the guidelines. Be aware of MOA as some patients may use OTC products to self-treat hypercholesterolemia

Sometimes used with sequestrants to ↓ Trigs and LDL when statins are not tolerated

Question 28

MOA of niacin?

Answer 28

B-vitamin is thought to decrease triglyceride production in the liver and inhibit HDL catabolism.

Question 29

What adverse effects are associated with Niacin?

Answer 29

Niacin flush (Flushing, pruritis)

Mild GI symptoms, muscle pain, rash, HA, sleep issues, anxiety, irritability, fatigue. Mild leukopenia and increased eosinophil levels.

Question 30

Indication for Adenosine triphosphate-citrate lyase (ACL) inhibitor [bempedoic acid (Nexletol)]?

Answer 30

hypercholesterolemia

Adjunct to diet/lifestyle interventions and max tolerated statins

Not enough data to support cardiovascular outcomes

Question 31

MOA for Adenosine triphosphate-citrate lyase (ACL) inhibitor [bempedoic acid (Nexletol)]?

Answer 31

Novel non-statin prodrug that reduces cholesterol production in the liver via the action of its active metabolite, ESP15228, ultimately leading to upregulation of LDL receptors and decreased LDL

Question 32

What adverse effects are associated with [bempedoic acid (Nexletol)]? When should it not be used?

Answer 32

Adverse Effects: back pain, extremity pain, elevated hepaticenzymes, gout, and tendon rupture. AFIB. GI distress.

Do not use it during pregnancy

Question 33

What is the key takeaway concerning lipid management?

Answer 33

It is highly individualized

Question 34

What is the target/goal with statins?

Answer 34

lower the low-density lipoprotein (LDL) levels

Question 35

What Monitoring do we want to do with patients on statins?

Answer 35

Recheck lipids ~ 4-12 weeks after dosage changes or after starting a statin, then every 3 to 12 months thereafter. Check the liver enzymes (aspartate aminotransferase and alanine aminotransferase) at baseline.

If symptoms suggest hepatotoxicity (e.g., unusual fatigue or weakness, loss of appetite, abdominal pain, dark-colored urine, or yellowing of skin or sclera), during therapy, recheck the liver enzymes, total bilirubin, and alkaline phosphatase.

Question 36

What instructions do you need to give your patients concerning bile acid sequestrants (Welchol) concerning administration?

Answer 36

As bile acid resins block cholesterol reabsorption from food, they must be taken during meals. Avoid taking them with other medications (e.g., thyroid, antibiotics), as this can block their absorption. Take these meds 1 hour before or four after other medications. Bile acid sequestrants may decrease the absorption of fat-soluble vitamins. Take vitamins four or more hours before bile acid resins.

Question 37

How do we reduce chance of “Niacin Flush”

Answer 37

“start low, go slow,” avoid concurrent ingestion of ethanol or hot or spicy foods and liquids. Take aspirin 30 minutes before dosing with a full glass of water

Question 38

What increases the risk of rhabdomyolysis?

Answer 38

renal impairment,
inadequately treated hypothyroidism,
taking other drugs associated with myopathy (e.g., colchicine),
on higher doses (as the higher the dose, the greater the risk).
Vtamin D and coenzyme Q deficiencies
>65 years.

Question 39

What lipid drugs can/cannot be used in the pediatric population?

Answer 39

Can Use: Statin (only certain ones), bile-acid binding (not preferred but ok)

Contraindicated: Niacin

Question 40

What anticipatory guidance is needed for a person with a functioning uterus and ovaries who is on antilipidemic?

Answer 40

Should be aware to call or d/c drugs as soon as they are aware of a pregnancy. Pt should know risk to fetus with statins.