Lecture 1: Drugs used for Dyslipidemias I | Quizlet

Atherosclerotis Cardiovascular Disease (ASCVD)

-risk with elevated LDL

-damage to endothelium with macrophages

-smooth muscle migration into arterial intima with proliferation

-cholesterol accumulation into macrophages

-formation of plaque

Statins

HMG-CoA Reductase Inhibitors

Statins

-decrease hepatic cholesterol synthesis

-blocks conversion of 3-hydroxy-3-methyl-glutaryl-coenzyme A to Mevalonate

-upregulation of LDL receptors ---> increase LDL clearance and decrease VLDL synthesis

Statins

-indications: Dyslipidemias, familial hypercholesterolemia

-primary and secondary prevention of cardiovascular events and ASCVD

-decreased LDL and TGs

-increases HDL

Statin

It is standard practice to initiate a ______________ immediately after acute coronary syndromes, regardless of lipid levels

>240

what is considered high total cholesterol levels?

<40

what is considered low HDL levels?

>190

what is considered high LDL cholesterol levels?

>200

what is considered high TG levels?

Pancreatitis

increased risk with TGs > 500-1000

-Decreased Oxidative Stress

-Decrease Vascular Inflammation

-Increase Stability of Atherosclerotic Lesions/Plaques

aside from lowering LDL and TGs, what are some additional effects of statins?

-Atorvastatin

-Rosuvastatin

-high intensity statins

-lower LDL by >50%

-Atorvastatin

-Rosuvastatin

-Simvastatin

-Pravastatin

-Lovastatin

-Fluvastatin

-Pitavastatin

-moderate intensity statins

-lower LDL by 30-50%

-Simvastatin

-Pravastatin

-Lovastatin

-Fluvastatin

-Pitavastatin

-Low intensity statins

-lower LDL on average by <30%

Statins

Adverse effects:

-Myalgias, Myositis, Myopathy, Rhabdomyolysis (SAMS)

-increased liver enzymes (liver failure)

-new onset diabetes mellitus

-GI upset, abdominal pain, nausea, diarrhea

Statin Associated Muscle Symptoms (SAMS)

risk factors for ______________________:

-conditions that increase statin concentrations or decrease muscle mass

-ex: advanced age, female, physical disabilities, hypothyroidism

-Acute Liver Disease

-Breast Feeding

CIs for statins

if the benefits outweigh the risks

can you use statins during pregnancy?

Statins

Drug interactions with ________________:

-gemifibrozil

-niacin

-amiodarone

-colchicine

-red yeast rice or alcohol

-CYP3A4 inhibitors/inducers

-CYP2C9 Inducers/inhibitors

-warfarin

Ezetimibe

-cholesterol absorption inhibitor

-inhibits absorption of dietary and biliary cholesterol from intestine at the brush border cells

Ezetimibe

MOA: binds to Niemann-Pick C1-like 1 to prevent dietary cholesterol from binding, which decreases cholesterol delivered to liver and increases expression of LDL receptors

Ezetimibe

-decreases LDL

-no effect on HDL

-slight decrease in TGs

-Indications: hyperlipidemia, familial hypercholesterolemia

-can be used alone or in combo with statins

Ezetimibe

-CI: moderate to severe liver impairment

-AEs: well tolerated, diarrhea, reversible hepatic impairment

Gemifibrozil

the only drug interaction associated with Ezetimibe

PCSK9 Inhibitor Antibodies

Evolocumab and Alirocumab

PCSK9 Inhibitor Antibodies

-monoclonal antibodies

-inhibits PCSK9 from degrading LDL receptors

PCSK9 Inhibitor Antibodies

-decreases LDL

-indications: heterozygous familial hypercholesterolemia, ASCVD as an adjunct to diet and max tolerated statin therapy

PCSK9 Inhibitor Antibodies

-administed by SQ injection every 2-4 weeks

-AEs: injection site pain/rxn, hypersensitivity reactions

-Costly

Odyssey-Outcomes Trial

Showed that Alirocumab improves CV outcomes

Small Interfering RNA (siRNA)

Inclisiran

Inclisiran

-siRNA that inhibits production of the PCSK9 protein in hepatocytes

-adjunct to diet and maximally tolerated statin therapy in adults with heterozygous familial hypercholesterolema or clinical ASCVD

Inclisiran

-AEs: injection site rxn, arthralgia, UTI, diarrhea, bronchitis, pain in extremity, and dyspnea

-discontinue if pt becomes pregnant bc may cause fetal harm

Bile Acid Sequestrant (BAS) Resins

-Colestipol

-Cholestyramine

-Colesevelam

Bile Acid Sequestrant (BAS) Resins

-resins that bind bile acids into an insoluble complex

-decrease LDL

-may increase HDL minimally

-may slightly increase TGs

Bile Acid Sequestrant (BAS) Resins

-indications: dyslipidemias, colesevelam for type 2 diabetes

-off label use: diarrhea from inadequate bile acid absorption, pruiritis from cholestasis

Bile Acid Sequestrant (BAS) Resins

-CIs: fasting TGs > 300 or history of bowel obstruction

-AEs: constipation, nausea, bloating, flatulence, epigastric fullness

Fiber

increasing __________________ can mitigate GI adverse effects of Bile Acid Sequestrant (BAS) Resins

Colesevelam

which Bile Acid Sequestrant (BAS) Resin has the least GI effects

LRC-CPPT

showed that Bile Acid Sequestrant (BAS) Resins improved CV outcomes

Niacin

-reduces hepatic synthesis of VLDL leading to decreased LDL production

-inhibits hormone sensitive lipase in adipose tissue to prevent breakdown of TGs into fatty acids

-decreases metabolism of HDL

-inhibits VLDL secretion

Niacin

-mainly increased HDL

-also decreases LDL and TGs

-indications: dyslipidemias

Niacin

AEs:

-flushing with pruritis

-hypotension

-N/V, diarrhea, GI distress, aggravation of PUD

-hyperuricemia/gout

-hyperglycemia/diabetes

-hepatotoxicity

-acanthosis nigricans with high doses

Niacin

CIs:

-active hepatic disease

-unexplained transminitis

-active peptic ulcer

-arterial hemorrhage

Immediate Release

what form of niacin has the lowest incidence of hepatotoxicity, but greatest incidence of flushing

Sustained Release

what form of niacin has the highest risk for hepatotoxicity and issues with flushing

Extended Release

what form of niacin has a low incidence of flushing and hepatotoxicity

-premedicated with NSAID or aspirin

-initiate low dose and titrate over weeks

-use extended release form

-take with food

-avoid hot liquids and alcohol

strategies to prevent Niacin-induced flushing and pruritis

AIM-HIGH

showed that there is no difference in CV outcome when Niacin is added

HPS 2-THRIVE

-showed there is no difference in first major vascular event when extended release niacin-laropiprant added to stain therapy

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