Dyslipidemia First Quiz on Objectives PDF

​ Pravastatin undergoes minimal first-pass metabolism as it is hydrophilic, unlike atorvastatin, simvastatin, or lovastatin, which are lipophilic and extensively metabolized by CYP450 enzymes. ​ First-pass metabolism reduces the bioavailability of lipophilic statins like simvastatin...

​ Pravastatin undergoes minimal first-pass metabolism as it is hydrophilic, unlike atorvastatin, simvastatin, or lovastatin, which are lipophilic and extensively metabolized by CYP450 enzymes. ​ First-pass metabolism reduces the bioavailability of lipophilic statins like simvastatin and atorvastatin, limiting the amount of drug reaching systemic circulation. ​ Atorvastatin is predominantly metabolized by CYP3A4, making it susceptible to interactions with CYP3A4 inhibitors like grapefruit juice. ​ Rosuvastatin undergoes minimal CYP metabolism (CYP2C9 and CYP2C19) and is primarily excreted unchanged via the kidneys. ​ Both lovastatin and simvastatin are prodrugs hydrolyzed in the liver to their active beta-hydroxy acid form ​ Fenofibrate is hydrolyzed in the liver to its active metabolite, fenofibric acid, which lowers triglycerides. ​ Bile acid sequestrants bind bile acids in the gut, preventing their reabsorption and forcing the liver to convert cholesterol into bile acids, reducing LDL-C. ​ Common side effects of bile acid sequestrants include gastrointestinal discomfort, especially constipation. ​ Nicotinic acid decreases lipolysis in adipose tissue, reducing free fatty acid availability for triglyceride synthesis. ​ Nicotinamide is a vitamin supplement and lacks the lipid-modifying effects of nicotinic acid. ​ Sustained-release niacin increases the risk of hepatotoxicity compared to immediate- or extended-release formulations ​ Flushing occurs due to prostaglandin-mediated vasodilation in the skin. ​ Flushing is associated with the conjugation pathway leading to nicotinuric acid production. ​ Sustained-release niacin undergoes amidation, producing metabolites linked to hepatotoxicity. ​ EPA reduces hepatic VLDL synthesis and lowers triglycerides effectively. ​ Omega-3 fatty acids reduce triglycerides by decreasing hepatic VLDL production. ​ PCSK9 inhibitors are indicated for patients with homozygous familial hypercholesterolemia or clinical ASCVD requiring further LDL-C reduction. ​ Evolocumab is FDA-approved for clinical ASCVD and familial hypercholesterolemia. ​ PCSK9 mAbs prevent degradation of LDL receptors, increasing their availability for LDL-C clearance. ​ Inclisiran silences the gene responsible for PCSK9 production, reducing circulating PCSK9 levels. ​ Bempedoic acid is activated by ATP-citrate lyase specifically in the liver, reducing LDL-C without muscle activation, minimizing myopathy risk. ​ Bempedoic acid avoids muscle-related side effects due to its liver-specific activation and lack of uptake in muscle cells. ​ Phase I metabolism involves reactions like oxidation, hydroxylation, or reduction, often mediated by CYP450 enzymes. ​ Phase II involves conjugation (e.g., glucuronidation or sulfation), making drugs more water-soluble for excretion. ​ Rosuvastatin and fluvastatin are primarily metabolized by CYP2C9, with minimal involvement of CYP3A4. ​ Ezetimibe undergoes glucuronidation in the intestinal wall and liver, converting into its active metabolite. ​ Statins are contraindicated in pregnancy and lactation due to their potential to harm fetal development. ​ Fibrates are contraindicated in patients with active liver disease, gallbladder disease, or severe renal dysfunction. ​ Statins and fibrates together increase the risk of myopathy due to overlapping metabolic pathways and muscle toxicity. ​ Gemfibrozil inhibits glucuronidation, reducing statin clearance and increasing myopathy risk. ​ Grapefruit juice inhibits CYP3A4, leading to increased plasma levels of lipophilic statins like atorvastatin and simvastatin. ​ Chronic kidney disease increases the risk of statin-induced myopathy due to impaired drug clearance. ​ Primary prevention aims to reduce ASCVD risk in patients without established disease but with high LDL-C or risk factors. ​ Secondary prevention involves managing patients with established ASCVD to prevent further cardiovascular events. ​ Clinical ASCVD includes conditions like coronary artery disease, stroke, and peripheral artery disease, not isolated hypertriglyceridemia. ​ Coronary artery disease is a key form of clinical ASCVD, along with peripheral arterial disease and cerebrovascular disease ​ LDL-C reduction is the main focus of dyslipidemia treatment due to its strong correlation with ASCVD risk. ​ In high-risk patients, the LDL-C target is