Pharmacology I: Hyperlipidemia Drugs
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Questions and Answers

What is the effect of oxidized LDL on nitric oxide expression?

  • Enhances the degradation of nitric oxide
  • Increases nitric oxide expression
  • Inhibits the expression of nitric oxide (correct)
  • Has no effect on nitric oxide expression

    • Which of the following is NOT a consequence of endothelial dysfunction and cellular interactions?

  • Atherosclerosis
  • Cancer (correct)
  • Fibrous plaque formation
  • Angina

    • What is the function of apolipoproteins on the surface of lipoproteins?

  • To inhibit the breakdown of triglycerides
  • To increase the synthesis of cholesterol ester
  • To serve as ligands for binding to receptors on cell surfaces (correct)
  • To decrease the expression of endothelin

    • What is the composition of the core of atherosclerotic plaques?

    <p>Lipids, collagen, calcium, and inflammatory cells</p> Signup and view all the answers

    What is the consequence of a weakened or vulnerable plaque?

    <p>Plaque rupture and coronary thrombosis</p> Signup and view all the answers

    What is the effect of oxidized LDL on macrophages?

    <p>Toxic to macrophages if highly oxidized</p> Signup and view all the answers

    What is the main function of apolipoproteins as cofactors?

    <p>To inhibit the breakdown of triglycerides</p> Signup and view all the answers

    What is the outcome of repeated injury and repair within an atherosclerotic plaque?

    <p>A fibrous cap protecting the underlying core of lipids</p> Signup and view all the answers

    What is the recommended dietary change for hypercholesterolemia?

    <p>Reduced intake of saturated fats and refined carbohydrates</p> Signup and view all the answers

    What is the effect of HMG-CoA reductase inhibitors on triglycerides?

    <p>Decrease triglycerides</p> Signup and view all the answers

    What is the site of action of HMG-CoA reductase inhibitors?

    <p>Liver</p> Signup and view all the answers

    Which of the following statins is almost completely absorbed?

    <p>Fluvastatin</p> Signup and view all the answers

    What is the effect of HMG-CoA reductase inhibitors on bone?

    <p>Prevent bone loss</p> Signup and view all the answers

    What is the recommended lifestyle change for hypercholesterolemia?

    <p>30 minutes of moderate-intensity exercise 3-7 days/week</p> Signup and view all the answers

    What is the effect of HMG-CoA reductase inhibitors on atherosclerotic lesions?

    <p>Decrease instability</p> Signup and view all the answers

    When should high-dose HMG-CoA reductase inhibitor therapy be initiated?

    <p>After acute coronary syndromes, regardless of lipid levels</p> Signup and view all the answers

    What is the primary effect of increased intracellular cholesterol on cholesterol synthesis?

    <p>It inhibits the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase</p> Signup and view all the answers

    What is the primary function of HDL in lipoprotein metabolism?

    <p>To transfer cholesterol to VLDL and LDL or to the liver for secretion into bile</p> Signup and view all the answers

    What is the effect of estrogens on apolipoprotein A-I production?

    <p>It increases apolipoprotein A-I production, leading to higher HDL levels</p> Signup and view all the answers

    What is the definition of dyslipidemia?

    <p>Elevated blood levels of lipoproteins (cholesterol, triglycerides, phospholipids)</p> Signup and view all the answers

    What is the primary role of cholesterol in the body?

    <p>To provide a source of free fatty acids</p> Signup and view all the answers

    What is the primary indication for drug therapy in hyperlipidemia?

    <p>The specific metabolic defect and its potential for causing atherosclerosis or pancreatitis</p> Signup and view all the answers

    What is the general cut-off value for elevated total cholesterol?

    <p>≥ 240 mg/dl (6.2 mmol/L)</p> Signup and view all the answers

    Which of the following is a major clinical consequence of hyperlipidemia?

    <p>Acute pancreatitis</p> Signup and view all the answers

    What is the general cut-off value for reduced high-density lipoprotein (HDL) cholesterol levels?

    <p>&lt; 40 mg/dl (1.03 mmol/L)</p> Signup and view all the answers

    What is the result of mildly oxidized LDL in the artery wall?

    <p>Recruitment of monocytes into the artery wall</p> Signup and view all the answers

    What is the beneficial effect of reducing total cholesterol, LDL, and increasing HDL levels on cardiovascular health?

    <p>It reduces mortality and CHD events</p> Signup and view all the answers

    What is the outcome of atherosclerotic lesions in the artery wall?

    <p>Acceleration of LDL oxidation</p> Signup and view all the answers

    What is the primary lipoprotein involved in the pathogenesis of atherosclerosis?

    <p>LDL</p> Signup and view all the answers

    What is the eventual clinical outcome of atherosclerosis?

    <p>All of the above</p> Signup and view all the answers

    Which of the following statins are indicated in patients with chronic kidney disease?

    <p>Atorvastatin, fluvastatin, pravastatin, and simvastatin</p> Signup and view all the answers

    Which of the following statins are not effective in patients who are homozygous for familial hypercholesterolemia?

    <p>All statins</p> Signup and view all the answers

    What is the common adverse effect of statins in patients with preexisting liver disease?

    <p>More severe liver damage</p> Signup and view all the answers

    What is the mechanism by which grapefruit juice increases the risk of hepatotoxicity and myopathy in patients taking statins?

    <p>Inhibition of cytochrome P450 activity</p> Signup and view all the answers

    Why should HMG-CoA reductase inhibitors be avoided in pregnancy?

    <p>Because there is no enough evidence that they are teratogenic, but we should be cautious</p> Signup and view all the answers

    What is the recommended approach to discuss the benefits and risks of statin therapy with patients during pregnancy?

    <p>Use shared decision making to discuss benefits versus risks</p> Signup and view all the answers

    Study Notes

    Background of Hyperlipidemia

    • Cholesterol and triglycerides are essential substrates for cell membrane formation and hormone synthesis, and provide a source of free fatty acids.
    • Cholesterol plays a central role in the pathogenesis of atherosclerosis.
    • Hyperlipidemia leads to acute pancreatitis and atherosclerosis, which can cause clinical outcomes such as angina, myocardial infarction (MI), arrhythmias, stroke, peripheral arterial disease, abdominal aortic aneurysm, and sudden death.

    Atherosclerosis

    • Atherosclerosis lesions arise from the transport and retention of plasma LDL through the endothelial cell layer into the extracellular matrix of the subendothelial space.
    • Oxidized LDL recruits monocytes into the artery wall, which transform into macrophages that accelerate LDL oxidation.
    • Oxidized LDL provokes an inflammatory response mediated by chemoattractants and cytokines.

    Lipoproteins

    • Lipoproteins are spherical particles with surfaces consisting largely of phospholipid, free cholesterol, and protein, and cores composed mostly of triglyceride and cholesterol ester.
    • Apolipoproteins (Apos) serve four main purposes: required for assembly and secretion of lipoproteins, serve as major structural components of lipoproteins, act as ligands for binding to receptors on cell surfaces, and can be cofactors for inhibition of enzymes involved in the breakdown of triglycerides from chylomicrons and VLDL.

    Cholesterol Synthesis

    • Increased intracellular cholesterol inhibits the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), the rate-limiting enzyme for intracellular cholesterol biosynthesis.
    • Increased intracellular cholesterol also reduces synthesis of LDL receptors and accelerates activity of acyl coenzyme-A: cholesterol acyltransferase to facilitate cholesterol storage within cells.

    HDL

    • HDL transfers cholesterol to either VLDL and LDL or to the liver for secretion into bile or conversion into bile acids.
    • Apolipoprotein A-I production is increased by estrogens, leading to higher HDL levels in women and individuals receiving estrogen.

    Dyslipidemia

    • Dyslipidemia is characterized by elevated blood levels of lipoproteins (cholesterol, triglycerides, phospholipids) and lipoprotein abnormalities.
    • Dyslipidemia can be primary (familial) or secondary, such as in diabetes mellitus.
    • Dyslipidemia is diagnosed when total cholesterol is ≥ 240 mg/dl, LDL cholesterol is > 160 mg/dl, triglyceride levels are > 200 mg/dl, and HDL cholesterol levels are < 40 mg/dl.

    Pharmacology of Drugs Used in Hyperlipidemia

    • HMG-CoA reductase inhibitors are the recommended drug of choice for hyperlipidemia and can reduce LDL-cholesterol by ≥ 50%.
    • These drugs work by reducing the production of cholesterol in the liver, leading to a decrease in LDL levels.
    • They also decrease triglycerides and increase HDL-C, and have been shown to prevent bone loss.

    Mechanism of Action of HMG-CoA Reductase Inhibitors

    • These drugs work mainly on the liver, where they inhibit HMG-CoA reductase, the rate-limiting enzyme for cholesterol biosynthesis.

    Pharmacokinetics of HMG-CoA Reductase Inhibitors

    • Lovastatin and simvastatin are inactive lactone prodrugs that are hydrolyzed in the gastrointestinal tract to the active β-hydroxyl derivatives.
    • Pravastatin, atorvastatin, fluvastatin, and rosuvastatin are active as given.
    • Absorption of the ingested doses varies from 40% to 75%, with the exception of fluvastatin, which is almost completely absorbed.
    • Most of the absorbed dose is excreted in the bile, with 5–20% excreted in the urine.
    • Plasma half-lives of these drugs range from 1 to 3 hours, except for atorvastatin (14 hours), pitavastatin (12 hours), and rosuvastatin (19 hours).

    Clinical Use of HMG-CoA Reductase Inhibitors

    • These drugs are effective in lowering plasma cholesterol levels in all types of hyperlipidemias.
    • However, patients who are homozygous for familial hypercholesterolemia lack LDL receptors and, therefore, benefit much less from treatment with these drugs.

    Adverse Effects of HMG-CoA Reductase Inhibitors

    • Mild elevations of serum aminotransferases are common but are not often associated with hepatic damage.
    • Patients with preexisting liver diseases may suffer more.
    • An increase in creatine kinase (released from skeletal muscle) is noted in about 10% of patients; in a few, severe muscle pain and even rhabdomyolysis may occur.
    • Mild transient gastrointestinal symptoms, headache, sleep disturbances, and fatigue are also common.

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    13 Drugs for Hyperlipidemia (Zarqa University, 2021/2022) PDF

    Description

    This quiz covers the pharmacology of drugs used to treat hyperlipidemia, including their effects on cholesterol and triglycerides. It is a part of the Pharmacology I course at Zarqa University's Clinical Pharmacy Department.

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