Pharmacology Quiz: Antihyperlipidemic Drugs!

Gemfibrozil and Fenofibrate are classified as fibric acid derivatives. This classification is based on their chemical structure and mechanism of action. Fibric acid derivatives are commonly used to lower triglyceride levels and increase HDL cholesterol levels in patients with dyslipidemia. Niacin, Ezetimibe, and Simvastatin are not fibric acid derivatives, and they belong to different classes of drugs that are used for different purposes in the management of lipid disorders.

Statins are competitive inhibitors of hepatic HMG CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. They work by blocking the action of this enzyme, which reduces the production of cholesterol in the liver. This leads to a decrease in the amount of cholesterol in the bloodstream, helping to lower LDL (bad) cholesterol levels. Statins are commonly prescribed to patients with high cholesterol to reduce their risk of cardiovascular diseases. Ezetimibe, fibric acids, bile acid-binding resins, and niacin are not competitive inhibitors of hepatic HMG CoA reductase.

Statins have been shown to be teratogenic in rodents.

Increased excretion of bile acids creates a demand for more cholesterol to make more bile in the liver. More LDL receptors are made to endocytose more LDLs increasing the amount of cholesterol in the liver and decreasing plasma LDL levels.

Lipoproteins serve to transport lipids from tissue to tissue and participate in lipid metabolism. The inside of the particles contains varying amounts of neutral lipids, cholesterol esters, and triacylglycerols. There are 5 major classes of lipoproteins, namely chylomicrons, VLDL, IDL, LDL, and HDL, each having specific physiological and anatomical significance. Therefore, all of the statements mentioned above are true concerning lipoproteins.

Mechanism of Action: Selectively inhibits intestinal absorption of dietary and biliary cholesterol at the brush border of the small intestine. After oral administration, it is extensively converted to a pharmacologically active glucuronide in the small intestine and liver and is excreted mostly in the stool.

Hepatic lipase is responsible for the hydrolysis of triglycerides in HDL (high-density lipoprotein) and IDL (intermediate-density lipoprotein). It is primarily located in the liver. This enzyme plays a crucial role in lipid metabolism by breaking down triglycerides into free fatty acids and glycerol, which can then be utilized by the body for energy production or stored in adipose tissue. The hydrolysis of triglycerides by hepatic lipase in the liver helps regulate the levels of lipoproteins in the bloodstream, contributing to overall lipid homeostasis.

Most statin drugs are given at night because cholesterol synthesis increases during this time. Cholesterol is mainly synthesized in the liver, and its production is influenced by the circadian rhythm. The body produces more cholesterol at night, so taking statin drugs during this time helps to inhibit the production of cholesterol effectively. By targeting the peak period of cholesterol synthesis, statins can effectively lower cholesterol levels in the body and reduce the risk of cardiovascular diseases.

LDLs get oxidized in the arteries and form plaques.

The fabric acid derivatives have multiple effects on the body. They enhance the oxidation of fatty acids in the liver and muscle, which means that they help in breaking down fatty acids for energy production. They also reduce the rate of lipogenesis in the liver, which is the process of converting excess carbohydrates into fatty acids. Additionally, they increase the synthesis of Apo AI and II, which are proteins responsible for the production of high-density lipoproteins (HDL), also known as "good" cholesterol. Therefore, all of the options mentioned in the question are correct.

Taking an NSAID like Aspirin concurrently with Niacin can help avoid some of the adverse effects such as dyspepsia, skin flushing, and itching. NSAIDs have anti-inflammatory properties that can counteract the flushing and itching caused by Niacin. However, it is important to note that this method may not completely eliminate all adverse effects and should be done under the guidance of a healthcare professional.

IDLs, or intermediate-density lipoproteins, are formed from the hydrolysis of triglycerides from VLDL by LPL. They can either be taken up by the liver via LDL receptors or converted to LDL lipoproteins. Their main function is to serve as an intermediate for the synthesis of LDL.

Rhabdomyolysis = degeneration of muscle cells - heart - eventually results in death.

The major apolipoprotein is Apo B-100 which is recognized by the LDL surface receptor in the liver and extrahepatic tissues.

Fibrates are known to displace warfarin, leading to increased levels of warfarin in the blood. Warfarin is an anticoagulant medication used to prevent blood clots. When fibrates displace warfarin, it means that fibrates compete with warfarin for binding sites on proteins in the blood, resulting in less warfarin being able to bind to these proteins. This leads to an increase in the free, unbound fraction of warfarin in the blood, which can potentially increase its anticoagulant effects and risk of bleeding.

HDLs, or high-density lipoproteins, are considered a scavenger for cholesterol. They function by removing excess cholesterol from the bloodstream and tissues and transporting it back to the liver for disposal. This process helps to prevent the buildup of cholesterol in the arteries and reduces the risk of cardiovascular diseases. HDLs are often referred to as "good cholesterol" because higher levels of HDLs are associated with a lower risk of heart disease.

Oxidized LDLs have multiple effects in the body. They attract monocytes from the circulation to the sub-endothelial space, where the monocytes are converted into macrophages. These macrophages play a key role in the development of atherosclerosis. Oxidized LDLs also inhibit macrophage mobility, keeping them at the site of atherogenesis. This allows the macrophages to generate free radicals, which further oxidize the attached LDLs. Additionally, oxidized LDLs are taken up by macrophages and can be cytotoxic, causing damage to the endothelium. Therefore, all of the statements mentioned are correct.

Combination therapy would be required.

CETP (cholesterol ester transport protein) functions in transferring cholesteryl esters from HDL to LDL and VLDL in the plasma. This process helps in redistributing cholesterol throughout the body by moving it from HDL (high-density lipoprotein) to LDL (low-density lipoprotein) and VLDL (very low-density lipoprotein). The location of this function is in the plasma, where the exchange of cholesteryl esters occurs between different lipoproteins.

HDLs, or high-density lipoproteins, are synthesized in the liver and intestine and are the smallest lipoprotein. HDLs are responsible for transporting cholesterol from the body's tissues back to the liver, where it can be eliminated from the body. They are often referred to as "good cholesterol" because they help remove excess cholesterol from the bloodstream, reducing the risk of cardiovascular diseases.

Gout - see an increase in uric acid because it competes for excretion - Diabetes - glucose levels are affected - Gallbladder Disease - releases bile acids.

Cholestyramine and colestipol are bile acid sequestrants that interfere with the absorption of ezetimibe. These medications work by binding to bile acids in the intestine, preventing their reabsorption and promoting their excretion. Ezetimibe, on the other hand, works by inhibiting the absorption of cholesterol in the small intestine. When taken together, cholestyramine and colestipol can bind to ezetimibe and prevent its absorption, reducing its effectiveness. Therefore, it is recommended to take cholestyramine and colestipol at least 2 hours before or 4 hours after taking ezetimibe to ensure proper absorption of both medications.

Chylomicrons are the largest particles of low density lipoprotein (LDL). Their main function is to transport dietary lipids to tissues for use and storage. LDLs, HDLs, IDLs, and VLDLs are all types of lipoproteins, but chylomicrons specifically serve the purpose mentioned in the question.

High levels of VLDL (triglycerides >1000mg/dl) are indicative of a risk for pancreatitis. Pancreatitis is a condition characterized by inflammation of the pancreas. Elevated levels of VLDL can lead to the accumulation of triglycerides in the pancreas, causing inflammation and potentially leading to pancreatitis. This condition can be serious and may require medical intervention. It is important to monitor and manage VLDL levels to reduce the risk of pancreatitis and its associated complications.

On the tissue surface LPL hydrolyzes the triglycerides for transport into the tissues. The rest of the VLDL lipoprotein interacts with HDL to obtain more Apoc C and more Apo E, eventually forming IDL, a precursor for LDL. High levels of VLDL (triglycerides > 1000mg/dl) indicate a risk for pancreatitis.

Underneath the arterial epithelium, the LDLs can undergo oxidation and the oxidized LDLs cause major problems.

Atorvastatin, pravastatin, and fluvastatin are active drugs.

Statins are considered the most effective antihyperlipidemics with few side effects. They work by inhibiting an enzyme involved in cholesterol synthesis, thereby reducing the levels of LDL cholesterol in the blood. Statins have been extensively studied and have shown significant benefits in reducing the risk of cardiovascular events. They are generally well-tolerated, with only a small percentage of users experiencing side effects such as muscle pain or liver abnormalities. Other antihyperlipidemics, such as niacin, fibrates, bile acid-binding resins, and ezetimibe, may also be effective but may have more side effects or be less potent in lowering LDL cholesterol levels.

The drugs listed in the question are known to inhibit the cytochrome P450 enzyme CYP3A4. This enzyme is responsible for metabolizing statins, which are medications used to lower cholesterol levels. Therefore, when these drugs inhibit CYP3A4, they can interfere with the metabolism of statins, leading to higher levels of statins in the body. Among the given options, the correct answer is "Atovastatin, simvastatin, and lovastatin" because these three statins are metabolized by CYP3A4 and can be affected by the listed drugs.

Rosuvastatin and atorvastatin have longer half-lives compared to other statins, which means they stay in the body for a longer duration. This allows them to be given at any time of the day since their effects are sustained throughout the day. Other statins, such as simvastatin and fluvastatin, have shorter half-lives and need to be taken at specific times to maintain their effectiveness. Pravastatin and lovastatin also have shorter half-lives and therefore need to be taken at specific times.

The mobilization of FFA from peripheral adipose tissue to the liver is inhibited by nicotinic acid. The conversion of VLDL to LDL is decreased as a consequence of this decrease or an additional hepatic effect via nicotinic acid and the synthesis and secretion of VLDLs are reduced. Although the mechanism is unknown, nicotinic acid also increases serum HDL cholesterol concentrations by up to 30%.

Lipoprotein lipase is responsible for hydrolyzing triglycerides in chylomicrons and VLDL in the capillary endothelium. This enzyme breaks down these triglycerides into free fatty acids and glycerol, which can then be used by cells for energy or storage. This process occurs in the capillary endothelium, which is the thin layer of cells that lines the interior surface of blood vessels.

CII and E are the apolipoprotein components of chylomicrons that stimulate lipase. Apolipoprotein CII activates lipoprotein lipase, an enzyme that breaks down triglycerides in chylomicrons into free fatty acids and glycerol. Apolipoprotein E is responsible for the recognition and uptake of chylomicron remnants by the liver. Together, CII and E play crucial roles in the metabolism and clearance of chylomicrons from the bloodstream.

Pravastatin and rosuvastatin are not significantly metabolized by the cytochrome P450 system. This means that they are not affected by drugs or substances that induce or inhibit the activity of this system. As a result, their metabolism and effectiveness are not altered by the presence of other medications, reducing the risk of drug interactions.

Lovastatin and simvastatin have a high first pass extraction by the liver. First pass extraction refers to the metabolism of a drug by the liver before it enters the systemic circulation. In the case of lovastatin and simvastatin, they undergo extensive metabolism in the liver, which reduces their bioavailability. This means that a significant portion of the drugs is metabolized by the liver before it reaches the systemic circulation, resulting in a lower concentration of the active drug in the body.

AI is recognized by a scavenger receptor (SR-BI) on the liver and thus takes HDL into the liver. NO B-100!

LCAT (lecithin cholesterol acyl transferase) is an enzyme responsible for the esterification of free cholesterol to cholesteryl esters. This process occurs in the plasma. Esterification of cholesterol is important for its transport in the bloodstream and its incorporation into lipoproteins such as HDL (high-density lipoprotein). By converting free cholesterol into cholesteryl esters, LCAT facilitates the formation of HDL particles, which are involved in the reverse cholesterol transport pathway, removing excess cholesterol from peripheral tissues and delivering it to the liver for excretion.

Fibrates are a class of medications primarily used to reduce elevated levels of triglycerides and increase levels of high-density lipoproteins (HDLs). They work by activating a specific receptor in the liver, which leads to increased breakdown of triglycerides and decreased production of very low-density lipoproteins (VLDLs). Therefore, the principal indication for fibrates is the elevation of VLDLs, not the elevation of LDLs or reduction of HDLs. High blood cholesterol levels and high blood pressure are not specifically targeted by fibrates.

Statins increase bone growth - added benefit.

Rifampin is a drug that accelerates the metabolism of statins. It is an antibiotic commonly used to treat tuberculosis and other bacterial infections. Rifampin works by inducing liver enzymes that are responsible for breaking down drugs, including statins. This increased metabolism can lead to lower levels of statins in the body, reducing their effectiveness. Therefore, it is important to monitor statin levels and adjust the dosage accordingly when rifampin is co-administered.

Lovastatin and Simvastatin are able to penetrate the CNS. The other statins are not.

If a patient has high VLDLs (high triglycerides), don't start with these drugs because they also turn on the synthesis of triglycerides initially (due to liver compensation) - might be enough to push the patient into pancreatitis.

Niacin is the drug of choice for lowering VLDL levels in patients at risk of pancreatitis and for mixed elevations of LDLs and VLDLs and low levels of HDLs. Niacin is a B vitamin that has been shown to decrease VLDL production in the liver, leading to lower levels in the blood. It also increases HDL levels, which helps to further improve the lipid profile. Niacin is often used in combination with other lipid-lowering medications for optimal results. Fibric acids, ezetimibe, statins, and bile acid-binding resins are also used to lower cholesterol levels but are not specifically indicated for these particular lipid abnormalities.

Rosuvastatin and simvastatin are statins that increase HDL (high-density lipoprotein) levels, but not as much as niacin. HDL is often referred to as "good" cholesterol because it helps remove LDL (low-density lipoprotein) cholesterol from the arteries. Niacin is a B vitamin that is known to significantly increase HDL levels. Therefore, while rosuvastatin and simvastatin can improve HDL levels, they are not as effective as niacin in doing so.

Fluvastatin is the correct answer because it is metabolized by CYP2C9, which is an important enzyme in drug metabolism. This means that the effectiveness and side effects of fluvastatin may be influenced by other drugs that interact with CYP2C9. Compared to other statins, fluvastatin has fewer drug interactions, making it a safer option for patients who are taking other medications that may interact with statins.

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Chloride ion is released from the cationic quaternary ammonium binding site in exchange for bile acids. They form an insoluble complex with bile acids present in the intestine, preventing the reabsorption of bile acids.

Lovastatin, when combined with gemfibrozil or niacin, especially increases the risk of myopathy. This adverse effect is possible for all statins, but lovastatin has a higher risk when used in combination with gemfibrozil or niacin.

Atorvastatin has only 2% renal excretion and Fluvastatin has less than 6%.

It is the newest antihyperlipidemic and it is not yet known whether it decreases coronary artery disease. It may not be a long lasting drug.