Lipid lowering drugs (TBL) Flashcards
Why do we treat lipid disorders, and what are the main consequences of these disorders?
Lipid disorders are treated to prevent adverse events. Lowering triglycerides can help avoid pancreatitis, while lowering cholesterol reduces the risk of cardiovascular disease. Cholesterol deposits in arterial walls can lead to conditions like heart attacks, strokes, and peripheral arterial disease.
What is the primary cause of atherosclerosis, and how does it relate to cholesterol?
Atherosclerosis is mainly caused by deposits of cholesterol in arterial walls. Cholesterol build-up can lead to arterial obstruction, potentially resulting in conditions like myocardial infarction (heart attack), stroke, and peripheral arterial disease.
How does lowering cholesterol affect atherosclerotic disease progression and outcomes?
Numerous clinical trials have shown that lowering cholesterol can reduce the progression of atherosclerotic disease and improve long-term outcomes.
What are the drug classes discussed in this module for treating hyperlipidemia?
The drug classes discussed in this module include statins, bile acid sequestrants (resins), PCSK9 inhibitors, fibrates, niacin, and Omega-3 ethyl esters (fish oil).
How are the discussed drugs organized based on their lipid-lowering effects?
The drugs are organized into two categories: those that lower cholesterol and those that lower triglycerides. Statins are the first-line agents for lowering cholesterol, while other drugs can have various effects on LDL cholesterol and triglycerides.
Why do lipids travel in the bloodstream as lipoproteins?
Lipids are too hydrophobic to travel in the bloodstream by themselves, so they are transported within lipoprotein particles. These particles also facilitate docking and regulate the movement of lipids within the body.
What is the role of chylomicrons, VLDL, LDL, and HDL in lipid metabolism?
Chylomicrons transport triglycerides from the diet to the liver. The liver processes these lipids and exports triglycerides in VLDL particles. Cholesterol travels from the liver to the periphery in LDL particles, while cholesterol returns to the liver from the periphery in the form of HDL particles.
What is the liver’s role in lipid metabolism?
The liver serves as the central hub for lipid metabolism. It processes dietary lipids, exports triglycerides, synthesizes and exports cholesterol, and plays a vital role in overall lipid homeostasis.
What is the primary function of the liver regarding cholesterol, and why is it important to maintain a stable level of cholesterol?
The liver plays a central role in cholesterol homeostasis, ensuring a stable level of cholesterol. Cholesterol from the liver is used for various purposes in the body, including membrane formation, hormone production, and bile acid synthesis.
How does the liver obtain cholesterol, and what is the balance between de novo synthesis and dietary intake?
The liver gets cholesterol from two main sources: de novo synthesis (50%) and dietary intake (50%), primarily through the uptake of LDL particles from the bloodstream.
What is the primary mechanism of action of statins, and how do they affect cholesterol levels in the liver?
Statins are HMG-CoA reductase inhibitors that block cholesterol synthesis in the liver. By inhibiting this step, they lead to an increase in the number of LDL receptors on the liver’s surface, resulting in greater uptake of LDL from the bloodstream and reduced cholesterol levels.
What is the desired outcome of statin treatment for cholesterol management?
The desired outcome of statin treatment is to reduce elevated cholesterol levels in the bloodstream, protecting various parts of the body from the harmful effects of excess cholesterol.
How do statins affect the liver, and what is their mechanism of action?
Statins are HMG-CoA reductase inhibitors, and they block cholesterol synthesis in the liver. This leads to an increased number of LDL receptors on the liver’s surface, facilitating the uptake of LDL from the bloodstream to maintain stable cholesterol levels.
What are some potential adverse effects associated with statin use, and how do they impact patients?
Adverse effects of statins may include rhabdomyolysis, which leads to muscle pain and can result in dark urine due to myoglobin release. Liver dysfunction is another potential side effect, though routine monitoring frequency has been reduced. Statins should not be used during pregnancy and are excreted into breast milk. They can also slightly increase the risk of new-onset diabetes, but the cardiovascular benefits generally outweigh this risk.
What is the role of resins in lowering cholesterol, and how do they work in the body?
Resins, or bile acid sequestrants, work in the gut and bind to bile acids, preventing their reabsorption. This results in the loss of bile acids in the stool. To compensate for the loss, the body either synthesizes more cholesterol or takes up additional cholesterol from the bloodstream. Resins interfere with the recycling of bile acids, effectively reducing the cholesterol pool.
What is the impact of resins on triglyceride levels, and when should they not be used?
Resins can increase triglycerides and VLDL levels. Therefore, they should not be used in individuals with elevated triglyceride levels.
How do resins, or bile acid sequestrants, work to lower cholesterol?
Resins work in the gut by binding to bile acids, preventing their reabsorption. This leads to the loss of bile acids in the stool. To compensate for the loss of bile acids, the body must either synthesize more cholesterol or take up additional cholesterol from the bloodstream, thereby reducing the cholesterol pool.
What are some side effects associated with taking resins?
Resins can cause unpleasant side effects such as constipation and a bloated feeling. They can also affect the absorption of other drugs and fat-soluble vitamins, so patients need to be counseled on proper timing when taking medications.
In clinical trials, has the combination of a statin and a resin shown additional cardiovascular risk reduction compared to using either medication alone?
No, clinical trials have not demonstrated additional cardiovascular risk reduction by combining a statin and a resin. Using a statin as monotherapy is more effective in reducing cardiovascular morbidity and mortality.
Which individuals may be least responsive to statins and resins?
Individuals who are homozygous for non-functional LDL receptors (e.g., in familial hypercholesterolemia) may be least responsive to statins and resins, as these drugs rely on the presence and functionality of LDL receptors on the liver to take up cholesterol from the bloodstream.
What is a potential serious side effect of statin use, and what should healthcare providers advise patients about this side effect?
A potential serious side effect of statin use is myopathy, which can lead to severe muscle pain. Healthcare providers should counsel their patients to contact them if they experience muscle aches. Routine monitoring of liver enzymes for signs of liver toxicity is also recommended.
What is the mechanism of action of ezetimibe in lowering LDL cholesterol?
Ezetimibe interferes with a transporter responsible for cholesterol uptake in small intestinal cells. By inhibiting this transport, it reduces overall cholesterol levels in the body.
How does the efficacy of ezetimibe compare to that of statins in lowering LDL cholesterol?
Ezetimibe is less efficacious than statins and typically lowers LDL cholesterol by 15-25%. However, the reduction in LDL cholesterol is a surrogate measure, and clinical trial data have shown that adding ezetimibe to a statin can further lower cholesterol and reduce the risk of cardiovascular adverse events.
What is bempedoic acid, and how does it lower cholesterol?
Bempedoic acid is an ATP citrate lyase inhibitor indicated for individuals who cannot tolerate statins or need further cholesterol lowering. It inhibits cholesterol synthesis in the liver by blocking the formation of acetyl-CoA.
