Drug-induced pulmonary arterial hypertension: a primer for clinicians and scientists

Am J Physiol Lung Cell Mol Physiol. 2018 Jun 1;314(6):L967-L983. doi: 10.1152/ajplung.00553.2017. Epub 2018 Feb 8.


Drug-induced pulmonary arterial hypertension (D-PAH) is a form of World Health Organization Group 1 pulmonary hypertension (PH) defined by severe small vessel loss and obstructive vasculopathy, which leads to progressive right heart failure and death. To date, 16 different compounds have been associated with D-PAH, including anorexigens, recreational stimulants, and more recently, several Food and Drug Administration-approved medications. Although the clinical manifestation, pathology, and hemodynamic profile of D-PAH are indistinguishable from other forms of pulmonary arterial hypertension, its clinical course can be unpredictable and to some degree dependent on removal of the offending agent. Because only a subset of individuals develop D-PAH, it is probable that genetic susceptibilities play a role in the pathogenesis, but the characterization of the genetic factors responsible for these susceptibilities remains rudimentary. Besides aggressive treatment with PH-specific therapies, the major challenge in the management of D-PAH remains the early identification of compounds capable of injuring the pulmonary circulation in susceptible individuals. The implementation of pharmacovigilance, precision medicine strategies, and global warning systems will help facilitate the identification of high-risk drugs and incentivize regulatory strategies to prevent further outbreaks of D-PAH. The goal for this review is to inform clinicians and scientists of the prevalence of D-PAH and to highlight the growing number of common drugs that have been associated with the disease.

Keywords: drug-induced pulmonary hypertension; pathology; pharmacovigilance; prevention.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Endothelin Receptor Antagonists / adverse effects*
  • Endothelin Receptor Antagonists / therapeutic use
  • Humans
  • Hypertension, Pulmonary* / chemically induced
  • Hypertension, Pulmonary* / pathology
  • Hypertension, Pulmonary* / physiopathology
  • Phosphodiesterase 5 Inhibitors / adverse effects*
  • Phosphodiesterase 5 Inhibitors / therapeutic use
  • Pulmonary Circulation / drug effects*


  • Endothelin Receptor Antagonists
  • Phosphodiesterase 5 Inhibitors