Lipid Lowering Drugs Lecture Review

A set of vocabulary flashcards covering the biochemical roles of lipids, cholesterol biosynthesis, lipoprotein transport, and the mechanisms of action for various lipid-lowering pharmacological agents.

Lipids

Diverse biomolecules that are insoluble in $H_2O$ but readily soluble in nonpolar solvents, involved in energy storage and membrane structure.

Triglycerides

Esters of glycerol and fatty acids that serve as the main storage lipid in adipocytes.

Chylomicrons

Lipoproteins synthesized from dietary triglycerides and cholesterol in the intestine, where triglycerides constitute approximately 85\text{ %} of the complex.

NPC1L1

Nieman-Pick C1 like 1 protein, which facilitates the uptake of dietary cholesterol from the gastrointestinal tract.

HMG-CoA reductase

The enzyme that reduces 3-hydroxy-3-methyl-glutaryl CoA to mevalonate, acting as the first committed step in cholesterol synthesis.

VLDLs

Lipoproteins that transport endogenous triglycerides and are hydrolyzed by lipoprotein lipase at the capillary surface.

LDLs

The major carrier of cholesterol in blood that becomes atherogenic when modified by oxidation.

HDLs

Lipoproteins that transport cholesterol from peripheral cells to the liver, associated with a decreased risk of cardiovascular disease.

Reverse cholesterol transport

A process mediated by the ABCA1 transporter that transfers cellular cholesterol and phospholipids to lipid-poor apolipoproteins like apo A1.

Tangiers disease

A condition caused by mutations in the ABCA1 transporter.

Atherosclerosis

A build-up of cholesterol plaques that cause blood flow obstruction or acute occlusion of the artery if the plaque ruptures.

Dyslipidemia

Abnormally elevated levels of lipids, mainly cholesterol and triglycerides, in the blood; also known as hyperlipidemia.

Familial hypercholesterolemia

A primary dyslipidemia characterized by LDL receptor or Apo B receptor defects leading to reduced LDL clearance.

Bile acid binding resins

Cationic polymer resins, such as cholestyramine and colestipol, that bind non-covalently to negatively charged bile acids in the intestine.

Ezetimibe

A drug that blocks NPC1L1 in the brush border of enterocytes, reducing intestinal cholesterol absorption by approximately 50\text{ %}.

Statins

HMG-CoA reductase inhibitors that decrease hepatic cholesterol synthesis and up-regulate LDL receptor synthesis to increase plasma LDL clearance.

Rhabdomyolysis

A serious but rare muscle disturbance associated with statin and fibrate use that can lead to acute kidney injury due to myoglobin filtration.

Fibrates

Agonists at the Peroxisome proliferator-activated receptor $\alpha$ (PPAR$\alpha$) that increase the transcription of lipoprotein lipase and stimulate $\beta$-oxidative degradation of fatty acids.

Niacin

A water-soluble vitamin (Vitamin $B_3$) that inhibits hepatic triglyceride production and is the most effective agent for increasing $HDL\text{-}C$.

Orlistat

A pancreatic and intestinal lipase inhibitor indicated for obesity that reduces dietary fat absorption.

PCSK9 inhibitors

Agents like alirocumab and evolocumab that bind a pro-protein involved in LDL receptor regulation to increase the uptake of LDL-cholesterol from the blood.