Pharmacology: Lipid- Lowering Drugs, Animation

Mechanisms of action of Antihyperlipidemic agents: Statins, Bile-binding resins, Ezetimibe, Fibrates, PCSK9 inhibitors and Niacin.
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Lipid-lowering therapy aims to reduce the circulating levels of chylomicrons, VLDL, and LDL, but increase the level of HDL. Mechanisms of existing drugs include: inhibition of cholesterol or lipoprotein production; inhibition of intestinal cholesterol absorption; inhibition of bile reabsorption to promote cholesterol removal; and promotion of lipoprotein degradation.
Statins are typically the first-line therapy, they inhibit endogenous production of cholesterol. Statins are competitive inhibitors of HMG-CoA reductase - the enzyme that controls the rate-limiting step in cholesterol synthesis. As intracellular cholesterol decreases, the cells import more cholesterol from blood plasma to fulfill their needs, effectively lowering plasma LDL levels. Statins are best taken before bedtime, because cholesterol synthesis typically occurs during fasting at night. Common side effects include muscle pain and muscle injury which may increase with vigorous exercise. Other adverse effects include new development of diabetes and liver damage.
Another class of drugs are inhibitors of bile reuptake. Normally, about 95% of bile acids delivered to the duodenum are reabsorbed back into the blood. The 5% that is excreted in feces is compensated for by newly synthesized bile in the liver. Bile-binding resins adhere to negatively charged bile acids in small intestine, preventing them from being reabsorbed, thus promoting their excretion. As more bile is excreted in feces, the liver produces more new bile from cholesterol, effectively removing more cholesterol from the blood. These resins are best taken with meals. Common side effects include nausea, bloating, and stomach cramping. In addition, absorption of fat-soluble vitamins may be reduced; production of liver enzymes may also increase.
Ezetimibe inhibits the absorption of dietary and biliary cholesterol from the small intestine without affecting bile. It is taken with meals. Ezetimibe can cause fatigue, diarrhea, headache, runny nose, sore throat, body aches, and some other more serious but less common side effects.
Fibrates are agonists for PPAR-alpha. PPARs are transcription factors that mediate the effect of dietary fatty acids on lipoprotein metabolism. Activation of PPAR-alpha has several effects: it promotes degradation of triglyceride-rich particles by lipoprotein lipase, it reduces production of VLDL, and increases production of HDL by upregulating apolipoprotein A1 - the major protein component of HDL. Fibrates are usually taken before meals. Common side effects include indigestion, abdominal pain, fatigue, dizziness, leg cramp, and increased serum creatinine.
PCSK9 inhibitors are monoclonal antibodies that bind to and inhibit PCSK9. PCSK9 is an enzyme that promotes degradation of LDL receptors which are required for cellular uptake of LDL from the blood. Inhibition of PCSK9 increases LDL receptors, removing more LDL from blood plasma. These drugs are administered by subcutaneous injections. They can cause local injection site reactions such as erythema, pain, and bruising.
Niacin lowers plasma VLDL, LDL and triglyceride levels, and raises HDL significantly. Proposed mechanisms include: decreased triglyceride synthesis, decreased degradation of apolipoprotein A1, and increased activation of another PPAR, PPAR-gamma. This drug is taken with meals. Niacin is often poorly tolerated, with many side effects ranging from unpleasant to severe.

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[@waelfadlallah8939]

Great list of lipid lowering drugs. Excellent work 👏

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As Tom Dayspring always says, not a darn cell in your body needs cholesterol from your circulation system. The statin part can be improved.

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