Dyslipidemia Med. Chem.

Which statins are prodrugs?

Lovastatin and Simvastatin.

Which statin is most polar?

Pravastatin—due to OH and COOH groups.

Which statins have highest protein binding?

Lovastatin and Simvastatin (~95%).

Which statin is most hepatoselective?

Pravastatin—due to polarity and active transport.

What is the order of lipophilicity among statins?

Simvastatin > Lovastatin > Pravastatin.

Which statins are absorbed via passive diffusion?

Lovastatin, Simvastatin, Atorvastatin.

Which statins are absorbed via active transport?

Pravastatin and Rosuvastatin.

Which statins undergo renal excretion?

Pravastatin and Rosuvastatin.

What makes a statin hepatoselective?

Polarity and active transport via OATP1B1.

What is the chemical class of statins?

β-hydroxycarboxylic acids.

What is the chemical class of fibrates?

Phenoxyisobutyric acid analogs.

What is the chemical class of bempedoic acid?

Dicarboxylic acid derivative (prodrug).

What is the chemical class of ezetimibe?

β-lactam pharmacophore.

What is the chemical class of bile acid sequestrants?

Anion-exchange resins (cationic polymers).

What is the chemical class of PCSK9 inhibitors?

Monoclonal antibodies or siRNA (biologics).

What is the mechanism of statins?

Inhibit HMG-CoA reductase → ↓ cholesterol synthesis → ↑ LDL-R activity.

What is the mechanism of bempedoic acid?

Inhibits ATP citrate lyase → ↓ cholesterol synthesis upstream of statins.

What is the mechanism of fibrates?

Activate PPARα → ↑ ApoC2 & ApoA1 → ↑ VLDL breakdown → ↓ TG.

What is the mechanism of ezetimibe?

Blocks NPC1L1 transporter → ↓ dietary cholesterol absorption.

What is the mechanism of bile acid sequestrants?

Bind bile acids → ↑ cholesterol conversion → ↓ LDL.

What is the mechanism of PCSK9 inhibitors?

Prevent LDL receptor degradation → ↑ LDL clearance.

What functional group is essential for statin activity?

3,5-dihydroxycarboxylate mimics HMG-CoA transition state.

What functional group is essential for ezetimibe activity?

β-lactam ring and amide group for NPC1L1 binding.

What functional group is essential for fenofibrate activity?

Ester group hydrolyzed to active fenofibric acid.

What functional group is essential for bile acid resins?

Quaternary ammonium or ionizable amines for electrostatic binding.

Which statins are metabolized by CYP3A4?

Atorvastatin, Simvastatin.

Which statin is metabolized by CYP2C9?

Fluvastatin.

What is the bioavailability of statins?

Poor oral bioavailability due to first-pass metabolism.

What is the excretion route for lipophilic statins?

Biliary.

What is the excretion route for polar statins?

Renal.

What is the protein binding of lipophilic statins?

High.

What are clinically relevant metabolites of statins?

Active hydroxyacid forms.

What is the active metabolite of bempedoic acid?

Bempedoyl-CoA.

What is the active metabolite of fenofibrate?

Fenofibric acid.

What is the active metabolite of ezetimibe?

Ezetimibe-glucuronide.

Are PCSK9 inhibitors CYP-metabolized?

No—they are long-acting biologics.