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Related Concept Videos

Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors01:30

Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
Antihypertensive Drugs: Direct Renin Inhibitors01:25

Antihypertensive Drugs: Direct Renin Inhibitors

The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow01:26

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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...
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Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test

In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess the...
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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...

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Related Experiment Video

Updated: Jul 7, 2026

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
08:59

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Published on: December 3, 2020

Risk of liver dysfunction with ACE inhibitors based on real-world data from the MID-NET® in Japan.

Yuki Kinoshita1,2, Takashi Ando1,2, Kazuhiro Kajiyama1,2,3

  • 1Office of Pharmacovigilance I, Pharmaceuticals and Medical Devices Agency, Tokyo, Japan.

Hypertension Research : Official Journal of the Japanese Society of Hypertension
|October 10, 2025
PubMed
Summary

The risk of liver dysfunction from angiotensin-converting enzyme (ACE) inhibitors varies, suggesting it

Keywords:
Angiotensin-converting enzyme inhibitorsHypertensionLiver dysfunctionPharmacoepidemiologySafety measure

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Area of Science:

  • Pharmacovigilance
  • Real-world evidence
  • Cardiovascular drug safety

Background:

  • Package insert warnings for liver dysfunction differ among ACE inhibitors in Japan.
  • Previous risk assessments for ACE inhibitor-induced liver dysfunction are limited.

Purpose of the Study:

  • To evaluate the real-world risk of liver dysfunction associated with various ACE inhibitors prescribed in Japan.
  • To compare the risk of liver dysfunction between enalapril maleate and other ACE inhibitors.

Main Methods:

  • Retrospective cohort study using MID-NET® real-world data (2009-2019).
  • Included patients newly prescribed ACE inhibitors, excluding those with pre-existing liver dysfunction.
  • Used pairwise Cox proportional hazards models with high-dimensional propensity score weighting for adjusted hazard ratios (HRs).

Main Results:

  • Compared to enalapril maleate, HRs for liver dysfunction were: captopril 1.37, alacepril 0.71, imidapril hydrochloride 0.72, perindopril erbumine 1.08, and lisinopril hydrate 0.69.
  • Imidapril hydrochloride (HR 0.72; 95% CI 0.55-0.93) and lisinopril hydrate (HR 0.69; 95% CI 0.52-0.91) showed a statistically significant lower risk of liver dysfunction compared to the control.
  • The observed risks suggest liver dysfunction is unlikely to be a class effect of ACE inhibitors.

Conclusions:

  • The risk of liver dysfunction associated with ACE inhibitors is not uniform across all drugs in this class.
  • No additional safety measures are currently needed for ACE inhibitors without liver dysfunction warnings in Japan.
  • Continued pharmacovigilance is essential for the safe use of ACE inhibitors.