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Related Concept Videos

Hepatic Drug Excretion: Influencing Factors01:16

Hepatic Drug Excretion: Influencing Factors

The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
Hepatic Drug Excretion: Enterohepatic Cycling01:17

Hepatic Drug Excretion: Enterohepatic Cycling

Enterohepatic cycling involves the active secretion of drugs and their metabolites into the bile via transporters in the canalicular membrane of hepatocytes. This secretion is an integral part of the digestive process, releasing these substances into the gastrointestinal (GI) tract.
Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This...
Drug Biotransformation: Overview01:16

Drug Biotransformation: Overview

Pharmaceutical substances known as xenobiotics are predominantly lipophilic and nonionized. This enables them to permeate lipid bilayers, such as cell membranes, and interact with intracellular target receptors. Lipophilic drugs have an advantage in crossing biological barriers and reaching their intended sites of action. However, lipophilic drugs often have a restricted capacity for renal expulsion or elimination from the body. When these drugs enter the kidneys and undergo glomerular...
Drug Toxicity: Risk factors01:24

Drug Toxicity: Risk factors

Adverse Drug Reactions (ADRs) are potential complications that arise during pharmacotherapy, influenced by multiple risk factors. Age plays a significant role; both neonates and the elderly are at heightened risk due to their respective immature and diminished metabolic and elimination processes. Gender also impacts ADRs, with females experiencing a 1.5 to 1.7-fold greater risk than males, which may be linked to pharmacokinetic, pharmacodynamic, and hormonal differences. Notably, neonates, the...
Drug toxicity: Idiosyncratic Reactions01:16

Drug toxicity: Idiosyncratic Reactions

Idiosyncratic drug reactions represent abnormal chemical responses that vary significantly among individuals, ranging from extreme sensitivity to low doses to insensitivity to high doses. These reactions often occur due to the drug's covalent binding with serum proteins, forming a foreign hapten that triggers an immunotoxicological response. The variability in drug reactions has a strong pharmacogenetic foundation, with genetic differences crucial in how individuals metabolize drugs. For...

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Related Experiment Videos

Bicalutamide-associated fulminant hepatotoxicity.

Cindy L O'Bryant1, Thomas W Flaig, Kenneth J Utz

  • 1Department of Clinical Pharmacy, School of Pharmacy, University of Colorado-Denver, Aurora, CO 80045, USA. Cindy.OBryant@UCDenver.edu

Pharmacotherapy
|July 29, 2008
PubMed
Summary

Bicalutamide, used for prostate cancer, can rarely cause fatal liver damage. Close monitoring of liver function tests is crucial during treatment, even after prior successful use.

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Area of Science:

  • Pharmacology
  • Hepatology
  • Oncology

Background:

  • Bicalutamide is a nonsteroidal antiandrogen used in androgen deprivation therapy for metastatic prostate carcinoma.
  • It is often initiated with a luteinizing hormone-releasing hormone agonist to mitigate tumor flare symptoms.
  • Common side effects include gynecomastia, hot flashes, fatigue, and decreased libido, while liver function test elevations are less frequent.

Observation:

  • A 59-year-old man with metastatic prostate carcinoma developed severe abdominal pain, distension, and tenderness after 4 days of bicalutamide therapy.
  • His liver function tests became abnormal, and he progressed to tachycardia, hypotension, and multiorgan damage.
  • The patient died 8 days after starting bicalutamide due to multiorgan failure, likely from fulminant hepatotoxicity.

Findings:

  • The case suggests a probable causal relationship between bicalutamide and fulminant hepatotoxicity.
  • Liver function test abnormalities and symptoms of hepatotoxicity rapidly worsened, leading to critical illness.
  • Laboratory values indicated severe liver injury (ALT >40x ULN), acute kidney injury (Cr 4.2 mg/dL), and cardiac involvement (Troponin I 18 ng/mL).

Implications:

  • Fulminant hepatotoxicity is a rare but potentially fatal adverse effect of bicalutamide.
  • Liver function tests require monitoring before and during bicalutamide therapy.
  • Vigilance is necessary even in patients with no prior history of bicalutamide toxicity.