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Questions and Answers
What is the main mechanism by which hepatotoxic chemicals damage liver cells?
What is the main mechanism by which hepatotoxic chemicals damage liver cells?
What is the brand name of N-acetylcysteine (NAC)?
What is the brand name of N-acetylcysteine (NAC)?
What is the primary use of NAC in the treatment of acetaminophen overdose?
What is the primary use of NAC in the treatment of acetaminophen overdose?
What is the estimated market value of Silymarin in Germany?
What is the estimated market value of Silymarin in Germany?
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What is the common name of the plant Silybum marianum, which is used to treat liver diseases?
What is the common name of the plant Silybum marianum, which is used to treat liver diseases?
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What is the empirical formula of Silymarin?
What is the empirical formula of Silymarin?
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What is the result of Silymarin's action on RNA polymerase enzymes?
What is the result of Silymarin's action on RNA polymerase enzymes?
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What is the primary mechanism of NAC as an antidote in acetaminophen overdose?
What is the primary mechanism of NAC as an antidote in acetaminophen overdose?
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What is a common off-label use of NAC?
What is a common off-label use of NAC?
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What is the therapeutic implication of Silymarin's protein synthesis facilitatory action?
What is the therapeutic implication of Silymarin's protein synthesis facilitatory action?
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What is the pivotal pharmacological property of Silymarin?
What is the pivotal pharmacological property of Silymarin?
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What is a common adverse effect of NAC administration?
What is a common adverse effect of NAC administration?
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What is the type of liver injury that can be caused by hepatotoxic chemicals?
What is the type of liver injury that can be caused by hepatotoxic chemicals?
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What is the effect of Silymarin on hepatic stellate cells (HSC)?
What is the effect of Silymarin on hepatic stellate cells (HSC)?
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How does Silymarin regulate cellular and mitochondrial membrane permeability?
How does Silymarin regulate cellular and mitochondrial membrane permeability?
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What is the mechanism by which Silymarin prevents liver damage?
What is the mechanism by which Silymarin prevents liver damage?
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What is the main reason for using pancreatic enzyme supplements in patients with exocrine pancreatic insufficiency?
What is the main reason for using pancreatic enzyme supplements in patients with exocrine pancreatic insufficiency?
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What is the difference between pancreatin and pancrelipase?
What is the difference between pancreatin and pancrelipase?
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Why are enteric-coated preparations of pancrelipase commonly used?
Why are enteric-coated preparations of pancrelipase commonly used?
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What is the primary concern when dosing pancreatic enzyme supplements?
What is the primary concern when dosing pancreatic enzyme supplements?
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What is the main advantage of using pancrelipase over pancreatin?
What is the main advantage of using pancrelipase over pancreatin?
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Why are non-enteric-coated preparations of pancrelipase often given with acid suppression therapy?
Why are non-enteric-coated preparations of pancrelipase often given with acid suppression therapy?
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What is the main indication for using pancreatic enzyme supplements?
What is the main indication for using pancreatic enzyme supplements?
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What is the composition of pancreatic enzyme supplements?
What is the composition of pancreatic enzyme supplements?
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Study Notes
Hepatoprotective Agents
- Mechanisms of hepatotoxicity:
- Induction of lipid peroxidation and oxidative damages in liver cells
- Formation of reactive free oxygen radicals, leading to direct hepatotoxicity
- Increase in apoptosis
- Reduction in glutathione stores, an antioxidant in the human body
- Types of liver injury:
- Fatty liver
- Cholestasis
- Fibrosis
- Cirrhosis
- Necrosis
- Apoptosis
- Hepatitis
- Carcinogenesis
N-Acetylcysteine (NAC)
- Derivative of L-cysteine
- Brand names: Acetadote, Parvolex
- Pharmacologic category: Antidote, Mucolytic
- FDA-labelled indications:
- Acetaminophen/paracetamol overdose
- Adjunctive mucolytic therapy
- Diagnostic bronchial therapy
- Off-label use:
- Prevention of contrast-induced nephrotoxicity
- H. pylori infection
NAC as an Antidote
- Mechanism of action:
- Precursor of glutathione, increasing glutathione available for conjugation of NAPQI
- Enhancement of sulphate conjugation of unmetabolized acetaminophen
- Supply of thiol groups, which can directly bind with NAPQI in hepatocytes
- Involvement in scavenging of free radicals or changes in hepatic blood flow
Adverse Effects of NAC
- Oral:
- Drowsiness
- Chills/fever
- Nausea/vomiting
- IV:
- Anaphylactoid reactions
- Vomiting
- Bronchospasm
- Rhinorrhea
- Unpleasant odor
Silymarin
- Derived from Silybum marianum (milk thistle)
- Used in the treatment of liver diseases for centuries
- Complex mixture of four flavonolignan isomers: silybin, isosilybin, silydianin, and silychristin
- Structural similarity to steroid hormones believed to facilitate protein synthesis
Mechanism of Action of Silymarin
- Stimulation of protein synthesis:
- Entering the nucleus and acting on RNA polymerase enzymes
- Increasing ribosomal formation and hastening protein and DNA synthesis
- Anti-inflammation actions:
- Inhibition of 5-lipoxygenase pathway, leading to inhibition of leukotriene synthesis
- Strong inhibitory effect on LTB4, but not on TNF alpha or prostaglandin formation
- Antifibrotic action:
- Inhibition of hepatic stellate cell activation, preventing liver fibrosis
- Inhibition of protein kinase and other kinases involved in signal transduction
- Regulation of cellular and mitochondrial membrane permeability, increasing membrane stability against xenobiotic injury
Pancreatic Enzyme Supplements
- Indications:
- Exocrine pancreatic insufficiency
- Cystic fibrosis
- Chronic pancreatitis
- Pancreatic resection (pancreatectomy)
- Constituents:
- Amylase
- Lipase
- Proteases
- Types:
- Pancreatin (no longer used due to low efficiency)
- Pancrelipase (enriched preparation, 12 times more lipolytic activity and 4 times more proteolytic activity than pancreatin)
Pancrelipase
- Enteric-coated preparation:
- Rapidly and permanently inactivated by gastric acid
- Can be taken with meals and snacks without acid suppression therapy
- Formulations:
- Varying amounts of lipase, amylase, and protease
- Dosing:
- Individualized according to age, weight, degree of pancreatic insufficiency, and dietary fat intake
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Description
Learn about the mechanisms of hepatotoxicity, types of liver injury, and hepatoprotective agents like N-Acetylcysteine (NAC). Understand the role of antioxidants and oxidative damage in liver cells.
