# The change in the pharmacological significance of dihydralazine (Germany) and hydralazine (USA)

## TL;DR

This study explores why dihydralazine in Germany and hydralazine in the USA have become less important for treating high blood pressure due to their side effects.

## Contribution

The study provides a historical and comparative analysis of the decline in pharmacological importance of dihydralazine and hydralazine in two countries.

## Key findings

- Dihydralazine and hydralazine are now reserve drugs due to adverse drug reactions.
- Their use has shifted to chronic heart failure in African Americans.
- Dosages have decreased over time in both Germany and the USA.

## Abstract

Dihydralazine and hydralazine have been on the market since the 1950s. The primary indication for those is the treatment of hypertension. The aim of this study is to uncover the reasons why both, dihydralazine in Germany and hydralazine in the USA, have lost importance. The period under investigation covers the years 1955 to 2025. The standard work from the USA The Pharmacological Basis of Therapeutics (Goodman & Gilman) and three German pharmacology textbooks were selected: Allgemeine und spezielle Pharmakologie und Toxikologie (Aktories), Pharmakologie und Toxikologie (Lüllmann) and Allgemeine und Spezielle Pharmakologie und Toxikologie (Karow). Categories were created for the German and US textbooks. Clinical studies were used to evaluate the textbooks. In addition, the “Rote Liste” (Red List) of drugs was examined for each decade to identify changes. Guidelines and specialist information were also analyzed. Furthermore, learning platforms were examined about the learning content on dihydralazine. The textbooks show that dihydralazine is now only a reserve drug. Hydralazine is also no longer the drug of choice in the USA. The reason for the change in the evaluation of (di)hydralazines is the large number of adverse drug reactions (ADRs). In Goodman & Gilman, the areas of application increased from 1955 to 2023, whereas German pharmacology textbooks (Aktories) and (Lüllmann) show a decrease in indications over time. The (di)hydralazines now have an indication for chronic heart failure (CHF) in African Americans. The dose of hydralazine in the US and dihydralazine in Germany has been reduced over time. The (di)hydralazines have a wide spectrum of ADRs. Dihydralazine is no longer on the German drug list for medical exams. However, it is still covered on learning platforms. Dihydralazine in Germany and hydralazine in the USA have lost pharmacological importance but they are still used in individual situations, if tolerated, to reduce blood presssure.

The online version contains supplementary material available at 10.1007/s00210-025-04370-x.