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Questions and Answers
Which of the following statins is primarily metabolized by CYP3A4, making it susceptible to interactions with CYP3A4 inhibitors like grapefruit juice?
Which of the following statins is primarily metabolized by CYP3A4, making it susceptible to interactions with CYP3A4 inhibitors like grapefruit juice?
Which of the following drugs undergoes minimal CYP metabolism and is primarily excreted unchanged via the kidneys?
Which of the following drugs undergoes minimal CYP metabolism and is primarily excreted unchanged via the kidneys?
Which of the following drugs is a prodrug hydrolyzed in the liver to its active beta-hydroxy acid form?
Which of the following drugs is a prodrug hydrolyzed in the liver to its active beta-hydroxy acid form?
Which of the following drugs lowers triglycerides by decreasing hepatic VLDL production?
Which of the following drugs lowers triglycerides by decreasing hepatic VLDL production?
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Which of the following drugs reduces circulating PCSK9 levels by silencing the gene responsible for PCSK9 production?
Which of the following drugs reduces circulating PCSK9 levels by silencing the gene responsible for PCSK9 production?
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Which of the following statements is TRUE regarding the mechanism of action of PCSK9 inhibitors?
Which of the following statements is TRUE regarding the mechanism of action of PCSK9 inhibitors?
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Which of the following drugs is FDA-approved for both clinical ASCVD and familial hypercholesterolemia?
Which of the following drugs is FDA-approved for both clinical ASCVD and familial hypercholesterolemia?
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Which of the following drugs is associated with flushing as a side effect?
Which of the following drugs is associated with flushing as a side effect?
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Which mechanism explains why bempedoic acid minimizes myopathy risk?
Which mechanism explains why bempedoic acid minimizes myopathy risk?
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What potential side effect is associated with combining statins and fibrates?
What potential side effect is associated with combining statins and fibrates?
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Phase II metabolism primarily involves which of the following processes?
Phase II metabolism primarily involves which of the following processes?
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Which drug is known to inhibit glucuronidation and potentially lead to increased myopathy risk when combined with statins?
Which drug is known to inhibit glucuronidation and potentially lead to increased myopathy risk when combined with statins?
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What is the primary goal of primary prevention in dyslipidemia treatment?
What is the primary goal of primary prevention in dyslipidemia treatment?
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Which statement is true regarding clinical ASCVD?
Which statement is true regarding clinical ASCVD?
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How does grapefruit juice affect statin medications?
How does grapefruit juice affect statin medications?
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Which condition is not a contraindication for statin use?
Which condition is not a contraindication for statin use?
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Study Notes
Pravastatin Metabolism
- Pravastatin undergoes minimal first-pass metabolism, unlike lipophilic statins.
- First-pass metabolism reduces bioavailability of lipophilic statins.
- Rosuvastatin has minimal CYP metabolism and is primarily excreted unchanged.
Statin Interactions
- Atorvastatin is metabolized by CYP3A4, making it susceptible to grapefruit juice interactions.
- Lovastatin and simvastatin are prodrugs hydrolyzed to active beta-hydroxy acid forms in the liver.
Bile Acid Sequestrants
- Bind bile acids in the gut, preventing reabsorption.
- Force the liver to convert cholesterol to bile acids, reducing LDL-C.
- Common side effect is gastrointestinal discomfort, especially constipation.
Nicotinic Acid
- Decreases lipolysis in adipose tissue, reducing free fatty acid availability.
- Nicotinamide lacks lipid-modifying effects of nicotinic acid.
- Sustained-release niacin increases hepatotoxicity risk.
Flushing and Vasodilation
- Flushing is associated with prostaglandin-mediated vasodilation.
- Flushing occurs due to prostaglandin conjugation pathway to nicotinuric acid.
- Sustained-release niacin produces metabolites linked to hepatotoxicity.
Omega-3 Fatty Acids
- EPA reduces hepatic VLDL synthesis, lowering triglycerides effectively.
- Omega-3 fatty acids reduce triglycerides by decreasing hepatic VLDL production.
PCSK9 Inhibitors
- Indicate for patients with homozygous familial hypercholesterolemia or clinical ASCVD.
- Evolocumab is FDA approved for clinical ASCVD and familial hypercholesterolemia.
- PCSK9 inhibits LDL receptor degradation, increasing LDL-C clearance.
- Inclisiran reduces circulating PCSK9 by silencing PCSK9 production.
Bempedoic Acid
- Bempedoic acid is activated in the liver, reducing LDL-C without muscle activation.
- Avoids muscle-related side effects due to liver-specific activation and lack of muscle uptake.
- Phase I metabolism (oxidation, hydroxylation, or reduction) is often mediated by CYP450 enzymes.
Phase II Metabolism
- Phase II involves conjugation (glucuronidation or sulfation), making drugs more water-soluble for excretion.
- Rosuvastatin and fluvastatin primarily metabolized by CYP2C9.
- Ezetimibe undergoes glucuronidation in the intestinal wall and liver, forming an active metabolite.
Drug Contraindications and Risk Factors
- Statins and fibrates are contraindicated in pregnancy, lactation, and patients with active liver, gallbladder, or kidney disease.
- Gemfibrozil inhibits glucuronidation, increasing myopathy risk.
- Grapefruit juice inhibits CYP3A4, increasing plasma levels of lipophilic statins.
- Chronic kidney disease impairs drug clearance, increasing statin-induced myopathy risk.
- 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.
- Clinical ASCVD includes coronary artery disease, stroke, and peripheral artery disease not isolated hypertriglyceridemia.
- LDL-C reduction is the main focus in dyslipidemia treatment due to its strong correlation with ASCVD risk.
Statistical Data
- Studies show a 20% reduction in ASCVD risk for every 1 mmol/L (38.7 mg/dL) decrease in LDL-C.
- Patients with LDL-C ≥190 mg/dL fall into severe hypercholesterolemia and benefit from high-intensity statins regardless of ASCVD risk.
Study Recommendations
- Class I recommendations are supported by strong evidence, outweighing risks.
- Class C recommendations are based on limited data or consensus.
- High-risk ASCVD patients require LDL-C ≤70 mg/dL.
- Diabetic patients aged 40-75, with additional ASCVD risk factors, should receive high-intensity statin therapy.
- PCSK9 inhibitors are recommended for very high-risk ASCVD patients.
- Adding ezetimibe is recommended if LDL-C remains ≥100 mg/dL after high-intensity statin therapy.
Severe Hypertriglyceridemia
- Fibrates or omega-3 fatty acids are first-line options.
- In moderate hypertriglyceridemia, LDL-C reduction with statins are prioritized.
- Statin therapy effectiveness is monitored with liver function tests and CK levels when muscle symptoms are present.
- A ≥50% reduction in LDL-C indicates effective high-intensity statin therapy.
- Hydrophilic statins (pravastatin, rosuvastatin) have a lower muscle-related side effect risk.
- Soluble fiber improves lipid profiles by reducing LDL-C.
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Description
Test your knowledge on the metabolism of pravastatin and other statins in this quiz. Learn about their interactions, metabolic pathways, and effects on cholesterol levels. Dive into essential concepts regarding bile acid sequestrants and nicotinic acid.
