AGENTS USED IN DYSLIPIDEMIA CHAPTER SUMMARY

By: Melo L. Medecielo

Elevated triglycerides are known as hyperlipidemia, while raised lipoproteins cause

hyperlipoproteinemias. These conditions lead to clinical outcomes like atherosclerosis and acute
pancreatitis. Lipid-filled particles like LDL and IDL penetrate arterial walls, triggering
atherosclerosis, a primary cause of fatalities. The process involves the formation of atheromas
and is driven by changes in smooth muscle cells due to scavenger receptor-mediated endocytosis.
Free radicals alter molecules, promoting plaque formation and raising the risk of artery blockage.
Managing hyperlipidemia not only reduces coronary events but also slows plaque regression.
HDL, by aiding cholesterol retrieval and preventing lipoprotein oxidation, plays a role in
preventing atherosclerosis. Interestingly, reduced levels of HDL alone don't solely determine the
risk of atherosclerosis. Factors like impaired nitric oxide release, diabetes, and smoking also
contribute to atherosclerosis. To combat this, targeting modifiable risk factors with multifaceted
therapy is crucial. Aggressive medication to lower lipid levels not only fosters plaque regression
but also diminishes mortality from coronary events, although the process of atherogenesis
remains an ongoing concern.

The emphasis on liposomal fats like LDL and IDL penetrating arterial walls and fostering
atherosclerosis underscores the gravity of this process as a leading cause of mortality.
Understanding how these lipid-filled particles trigger the formation of atheromas through
scavenger receptor-mediated endocytosis in smooth muscle cells is pivotal. Furthermore, the
insight into free radicals altering molecules, promoting plaque formation, and elevating the risk
of artery blockage provides a clearer picture of the mechanisms underlying atherosclerosis.
Significance of managing hyperlipidemia, not only in reducing coronary events but also in
impeding plaque regression. It acknowledges the crucial role of HDL, not just in cholesterol
retrieval but also in preventing lipoprotein oxidation, thereby contributing to the prevention of
atherosclerosis. Moreover, the recognition that reduced HDL levels aren't the sole determinants
of atherosclerosis risk underscores the complexity of this condition. In addition to lipid
abnormalities, the paragraph underscores the role of other factors like impaired nitric oxide
release, diabetes, and smoking in fueling atherosclerosis. It stresses the need for multifaceted
therapeutic approaches that target various modifiable risk factors to effectively manage
atherosclerosis and its associated complications. It emphasizes the significant impact of
aggressive lipid-lowering medication in promoting plaque regression and reducing mortality
from coronary events, despite the ongoing challenges posed by the dynamic nature of
atherogenesis.

Statins:
● Statins are a class of drugs that primarily work by inhibiting an enzyme called
HMG-CoA reductase, a key player in cholesterol production in the liver. By reducing
 cholesterol synthesis, they effectively lower LDL cholesterol levels in the blood. This
class includes drugs like Atorvastatin, Simvastatin, Rosuvastatin, and Pitavastatin.
● Drugs: Atorvastatin, Simvastatin, Rosuvastatin, Pitavastatin
● MOA: Inhibit HMG-CoA reductase, a key enzyme in cholesterol synthesis,
reducing cholesterol production in the liver.
● Uses: Lower LDL cholesterol, total cholesterol, and triglycerides; increase HDL
cholesterol. Used in atherosclerotic cardiovascular disease (ASCVD),
hyperlipidemia, and for reducing cardiovascular events.
● Toxicology: Potential side effects include myopathy, elevated liver enzymes, and,
rarely, rhabdomyolysis. Some drugs within this class may have different potencies
and interactions with other medications.

Fibrates:
● Fibrates activate a receptor known as PPAR-alpha, which helps decrease triglyceride
synthesis while increasing HDL cholesterol levels.
● They are particularly effective in lowering triglycerides and increasing HDL cholesterol.
Fenofibrate and Gemfibrozil are common drugs in this class.
● Drugs: Fenofibrate, Gemfibrozil
● MOA: Activate peroxisome proliferator-activated receptor alpha (PPAR-alpha),
decreasing triglyceride synthesis and increasing HDL cholesterol.
● Uses: Reduce triglycerides, increase HDL cholesterol, and, to a lesser extent,
lower LDL cholesterol. Often used in hypertriglyceridemia and mixed
dyslipidemia.
● Toxicology: Potential side effects include gastrointestinal disturbances, myopathy,
and in rare cases, increased risk of gallstones. Gemfibrozil may have more drug
interactions compared to fenofibrate.

Bile Acid Sequestrants:

● These drugs, exemplified by Colestipol, work in the intestine by binding to bile acids,
preventing their reabsorption. This process leads to increased bile acid synthesis from
cholesterol in the liver, consequently lowering LDL cholesterol levels.
● Drug: Colestipol
● MOA: Bind to bile acids in the intestine, preventing their reabsorption and
promoting their excretion, which leads to increased bile acid synthesis using
cholesterol from the blood.
● Uses: Lower LDL cholesterol. Used in hypercholesterolemia and to reduce
cardiovascular risk.
● Toxicology: Side effects include gastrointestinal disturbances, constipation, and
interference with absorption of other medications.
Sterol Absorption Inhibitor:
● Ezetimibe is a sterol absorption inhibitor that acts in the small intestine by blocking the
NPC1L1 transporter, reducing cholesterol absorption from the diet.
● It's commonly used to lower LDL cholesterol and can be combined with statins or used as
an alternative for those intolerant to statins.
● Drug: Ezetimibe
● MOA: Inhibits the absorption of dietary cholesterol by blocking the NPC1L1
transporter in the small intestine, reducing cholesterol absorption.
● Uses: Lower LDL cholesterol. Often used in combination with statins or as an
alternative for those who can't tolerate statins.
● Toxicology: Generally well-tolerated, with rare instances of myopathy or
elevations in liver enzymes.

Niacin:
● Niacin, also known as vitamin B3, decreases the synthesis of VLDL and LDL cholesterol
in the liver while increasing HDL cholesterol levels.
● It has an impact on multiple lipoproteins, effectively reducing LDL cholesterol,
triglycerides, and increasing HDL cholesterol.
● Drug: Niacin
● MOA: Reduces the production of VLDL and LDL cholesterol by inhibiting
hepatic triglyceride synthesis. Also increases HDL cholesterol levels.
● Uses: Reduces LDL cholesterol, triglycerides, and increases HDL cholesterol.
Used in dyslipidemia.
● Toxicology: Can cause flushing, itching, gastrointestinal upset, and, at high doses,
liver toxicity.

PCSK9 Humanized Monoclonal Antibodies:

● These drugs, like Evolocumab, function by targeting the PCSK9 protein, which naturally
reduces the number of LDL receptors on liver cells. By blocking PCSK9, these
antibodies increase the number of receptors available to clear LDL cholesterol from the
blood, effectively lowering LDL levels.
● Drug: Evolocumab
● MOA: Blocks proprotein convertase subtilisin kexin 9 (PCSK9), which increases
the number of LDL receptors on hepatocytes, leading to increased LDL clearance
from the blood.
● Uses: Lower LDL cholesterol levels. Often used in familial hypercholesterolemia
or in individuals not achieving target LDL levels with other therapies.
● Toxicology: Generally well-tolerated, but side effects may include injection site
reactions, allergic reactions, and, in rare cases, neurocognitive events.