Anti-lipid agents

STATINS BABY

Hyperlipidemia (dyslipidemia)

high serum cholesterol (LDLs high or HDLs low) TGs may also be increased

HTN, diabetes, high waist circumference, high TGs, low HDL

What are red flags for metabolic syndrome

made from dietary fat, primarily TG

Describe the make up of chylomicrons

mostly TGs (less than chlylomicrons)

Describe the make up of VLDL (produced in the liver)

mostly cholesterol

Describe the make up of LDL (made from IDL)

mostly protein

Describe the make up of HDL (produced in the liver and intestine)

HMG-CoA reductase

What is the key enzyme in cholesterol production?

block HMG-CoA reductase, upregulate LDL receptors, decrease VLDL, increase HDL

What is the MOA for statins?

Increase clearance/decrease synthesis of VLDL, decrease uptake of HDL

What is the MOA for Niacins?

Increase clearance/decrease synthesis of VLDL, increase lipoprotein lipase activity

What is the MOA for Fibrates?

prevent reabsorption of bile acid, upregulate LDL-R

What is the MOA for bile acid binding resins?

selectively inhibits intestinal cholesterol absorption (NPC1L1 transporter)

What is the MOA for cholesterol absorption inhibitors?

prevents LDL receptor degradation

What is the MOA for PCSK9 inhibitors?

1st line for hypercholesterolemia, prophylactic use for peeps with DM or CVD

Uses for statins?

hypercholesterolemia, hypertriglyceridemia, primary adjunctive

Uses for niacin?

hypercholesterolemia, hypertriglyceridemia in patients with DM-II

Uses for fibrates?

additive to statin response

Uses bile acid binding resins?

Adjunctive to statins

Uses for cholesterol absorption inhibitors

fenofibrate, gemifibrozil

Examples of fibrates

cholestyramin, colestipol, solesevelam

Examples of bile acid binding resins

ezetimibe

Examples of cholesterol absorption inhibitors

fibrates, niacin

Whats the best choice for decreasing TGs

myalgia, myositis, myopathy, rhabdo (RARE), hepatotoxicity, hepatitis, DDIs, rash, GI intolerance, HA, teratogenic

Statin ADRs

atorvastatin, rosuvastatin

What are the high intensity statins?

atorvastatin, lovastatin, pravastatin (lesser extent), simvastatin

Which statins are metabolized by CYP3A4

fluvastatin, pitavastastin (lesser extent), rosuvastatin (lesser extent)

Which statins are metabolized by 2C9?

phase II (glucaronidation)

How is ezetimibe metabolized

increase LFTs

Downsides to combining ezetimibe and statins

Can lower statin dose and still hit goals

Upsides to combining ezetimibe and statins

HA, GI intolerance, gallstones, gemfirbozil increases myositis in statin use

ADRs of fibrates

HA, GI intolerance, itching, burning, hepatotoxicity, peptic ulcer, cutaneous flushing, increase glucose, increase uric acid, increases myositis with statins

ADRs of Niacins

constipation, GI intolerance, flatulence, steatorrhea, unpleasant taste, decrease absorption of ADEK

ADRs for resins?

diarrhea, arthralgia, increase LFTs

ADRs for ezetimibe

blocks the conformational change of LDL receptor

What is the MOA for PCSK9 inhibitors?

evolocumab, alirocumab, bococizumab

Examples of PCSK9 inhibitors

cannot be controlled with max statins, statins cannot be tolerated, FH

Indications for PCSK9 inhibitors

nasopharyngitis, upper RTIs, flu-illness, myalgia, back pain, arthralgia, HA, injection site reactions

ADRs for PCSK9 inhibitors (pretty rare)

inclisiran

What is a drug similar to a PCSK9 inhibitor that is a siRNA and can be added to max statin therapy for FH patients or ASCVD?

ACL inhibitors (bempedoic acid)

What blocks cholesterol creation at an earlier step than a statin?

increased uric acid, gout, myalgia, muscle spasm, constipation, UTI, tendon rupture

ADRs for ACL inhibitors

statins aren’t working or tolerated, FH

Indications of ACL inhibitor

EPA, DHA

What are some examples of omega-3 fatty acid products?

decrease hepatic production of TG, increase TG clearance

MOA for OM3FA

plant stanols/sterols, soluble fiber, OM3FA, control weight, increase physical activity, stop smoking, decrease intake of saturated fats and cholesterol

Lifestyle changes for dyslipidemia