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Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors01:28

Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors

Phosphodiesterase 5 (PDE5) inhibitors are potent enzymes that function to hydrolyze cyclic nucleotides to their corresponding 5' monophosphates. Their unique biochemical properties have been applied in treating Pulmonary Arterial Hypertension (PAH).
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
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Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment

Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
Factors Influencing Drug Absorption: Presystemic Elimination01:24

Factors Influencing Drug Absorption: Presystemic Elimination

The pharmacokinetic journey of oral drugs begins with a crucial first pass through the hepatic portal system, called the first-pass effect. This first pass significantly impacts bioavailability — the proportion of a drug that enters systemic circulation and is available for therapeutic action. The primary route sees the drug absorbed by intestinal membranes and then shunted to the liver via the hepatic portal vein. Here, pre-systemic elimination occurs as drugs face metabolism or biliary...
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Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug binding...
Drug toxicity: Drug–Drug Interaction01:30

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Preclinical Drug Testing in Scalable 3D Engineered Muscle Tissues
08:07

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Published on: April 7, 2023

Initially obscure hepatotoxicity attributed to sildenafil.

Frank H J Wolfhagen1, Hestia G Vermeulen, Rob A de Man

  • 1Department of Gastroenterology, Albert Schweitzer Hospital, Dordrecht, Rotterdam, The Netherlands. frankwolfhagen@gmail.com

European Journal of Gastroenterology & Hepatology
|August 6, 2008
PubMed
Summary
This summary is machine-generated.

Sildenafil use can cause severe liver injury, presenting as jaundice and malaise. Patients may not disclose sildenafil use, complicating diagnosis of drug-induced liver injury.

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Last Updated: Jul 3, 2026

Preclinical Drug Testing in Scalable 3D Engineered Muscle Tissues
08:07

Preclinical Drug Testing in Scalable 3D Engineered Muscle Tissues

Published on: April 7, 2023

Area of Science:

  • Hepatology
  • Clinical Pharmacology

Background:

  • Drug-induced liver injury (DILI) is a significant clinical concern.
  • Sildenafil is a widely used phosphodiesterase type 5 inhibitor.

Observation:

  • A patient presented with malaise, severe jaundice, and pruritus.
  • The symptoms were attributed to undisclosed sildenafil use.

Findings:

  • The liver injury exhibited a hepatocanalicular pattern.
  • Hepatocellular liver tests and extensive cholestasis on biopsy were noted.

Implications:

  • Clinicians should consider sildenafil as a potential cause of hepatotoxicity.
  • Open communication regarding medication use is crucial for accurate diagnosis.