Cardio Exam 2: Dyslipidemia Elsaid WRITTEN NOTES

What are the dyslipidemia meds/classes? (9)

Ezetimibe, PCSK9 Inhibitors, Inclisiran, Bempedoic Acid, BAS, Fenofibrate, Gemfibrozil, Nicotinic Acid, and Omega-3 FAs

Ezetimibe MOA?

Inhibits cholesterol absorption in the small intestines

Ezetimibe other MOA info?

NPC1L1 (becomes inhibited) = cholesterol uptake

NPC1L1 is a _____.

sterol transporter

Ezetimibe effects?

Decreases cholesterol to the liver, increases plasma cholesterol’s clearance, and minimal GI effects

Ezetimibe other info?

Efficacy: Atorvastatin (80 mg) = Atorvastatin/Ezetimibe (20/10 mg)

What are the PCSK9 Inhibitor drugs?

Alirocumab and Evolocumab

Alirocumab is a _____ drug.

PCSK9 Inhibitor

Evolocumab is a _____ drug.

PCSK9 Inhibitor

PCSK9 Inhibitor MOA?

Chaperone proteins made in the liver and are metabolized to small peptides and AAs

PCSK9 Inhibitor specific MOA?

Clears PCSK9 protein and LDL-C

PCSK9 Inhibitor Formulation + Frequency?

SQ injection every 2-4 weeks

PCSK9 Inhibitor other info?

Fully humanized mAbs and no renal elimination

Inclisiran MOA sequence?

Passenger Strand: 2 RNA , then GalNAc, then targeted hepatic delivery
Hepatocyte: Passenger strand dissociates from guide strand. then guide strand assembles and binds to RISC, then, RISC-guided strand binds PCSK9 mRNA and blocks translation, then degradation of PCSK9 mRNA, then no PCSK9

KNOW

Bempedoic Acid MOA?

ATL Inhibitor

ATL stands for….

Adenosine Triphosphate-Citrate Lyase

Bempedoic Acid MOA sequence?

Inhibits cholesterol synthesis in the liver upstream of HMG-CoA Reductase, then increases LDL receptors, then decreases plasma LDL-C

Bempedoic Acid when Activated?

Inhibits ACL enzyme and decreases cholesterol synthesis in hepatocytes

Bempedoic Acid other info?

Prodrug activated by ACSVL1 in liver, there’s no ACSVL1 enzyme in myocytes, and used for adults with HeFH or established ASCVD

BAS are _____.

resins

BAS MOA?

Increases hepatic uptake of serum cholesterol by creating an insoluble complex with bile acids and salts that prevents their reabsorption from the intestine

BAS secretion/reabsorption info?

>90% of Bile Acids secreted into intestine are reabsorbed

BAS Effects?

GI adverse effects such as constipation, bloating, gas, and nausea

BAS C/I?

TG >300 mg/dL caused by pancreatitis

How are bile acids made?

Increase BA excretion and Hepatic conversion of cholesterol

Fenofibrate MOA sequence?

Nucleus to PPAR Nuclear Factor to Activation to Increasing LPL to hydrolyzed TG levels to Lipoprotein metabolism

Fenofibrate MOA sequence shortened?

Liver to VLDL to apoC-III to LPL to LDL

LPL = _____, which decreases _____

LPL is in the _____

Fenofibrate, TGs, endothelium of blood vessels

Gemfibrozil vs Fenofibrate?

Same efficacy as Fenofibrate with no statins, but Fenofibrate preferred in combo with statins

Nicotinic Acid MOA?

Inhibition of free FA release from adipose tissue that increases LPL activity and niacin inhibits TGs to FAs to decreases VLDL/LDL

Nicotinic Acid shortened MOA?

Decreased hepatic production of VLDL and apoB

Nicotinic Acid Effects?

Too many adverse effects such as Flushing/Vasodilation, leading to increased HR and reflex tachycardia

Omega-3 FAs MOA?

DGAT inhibits TG-synthesizing enzymes, which increases LPL and decreases hepatic synthesis and secretion of VLDL particles

Omega-3 FAs ingredients?

Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA)

Omega-3 FAs other info?

Rx (NOT to OTC med)

High-Intensity Statin MOA?

Blocks cholesterol synthesis and increases HDL to take cholesterol plaques back to the liver

Statins = Pleotropic Effects?

• Decreased _____ and _____ risk

• Inhibition of _____ and/or _____ generation

• Stabilize atherosclerotic _____

inflammation, blood clot formation, platelet aggregation, thrombin, plaques

TG-Lowering Agents?

Lovaza (ethyl ester), Epanova (FA), Vascepa, Gemfibrozol, Fenofibrate, and Niacin

REMEMBER

• _____ = HMG CoA Reductase inhibitors

• _____ = ACL inhibitor

• _____ = PCSK9 Inhibiting Agents

• _____ = Generics of BAS

• _____ = Brands of BAS

• _____ = Cholesterol Absorption Inhibitor

• _____ = TG-Lowering Agents

• _____ = EPA+DHA Ethyl Ester

• _____ = EPA+DHA FA

• _____ = Icosapent Ethyl

Statins

Bempedoic Acid

-rocumab and Inclisiran

Colesevelam, Colestipol, and Cholestyramine

Welchol, Colestid, and Questran

Ezetimibe

Fibrates, Omega-3 FAs, and Niacin

Lovaza

Epanova

Vascepa