Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Jun 1;314(6):L967-L983.
doi: 10.1152/ajplung.00553.2017. Epub 2018 Feb 8.

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

Mark E Orcholski  1   2   3 , Ke Yuan  1   2   3 , Charlotte Rajasingh  4 , Halley Tsai  1 , Elya A Shamskhou  1   2   3 , Navneet K Dhillon  5 , Norbert F Voelkel  6 , Roham T Zamanian  1   2   3 , Vinicio A de Jesus Perez  1   2   3
Affiliations

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

Mark E Orcholski et al. Am J Physiol Lung Cell Mol Physiol. .

Abstract

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.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
Molecular structure of amphetamine-derived anorexinogens.
Fig. 2.
Fig. 2.
Carboxylesterase 1 (CES1) expression is reduced in vascular lesions of methamphetamine-induced pulmonary arterial hypertension (METH-PAH). A: representative immunofluorescence studies of lung sections stained for cytochrome P-450 (CYP) 2D6 (red) obtained from healthy donor and METH-PAH patients. No difference was seen among our 4 METH-PAH patients. B: representative immunofluorescence studies of lung sections stained for CES1 (red) obtained from healthy donor (top) and 4 METH-PAH patients. CD31 (green) stains for endothelial cells. Scale bar = 25 μm.
Fig. 3.
Fig. 3.
Proposed model of the role of CES1 in METH-PAH.
Fig. 4.
Fig. 4.
The aryl hydrocarbon receptor (Ahr)-aryl hydrocarbon receptor nuclear translocator (ARNT)-CYP450 signaling pathway and its proposed role in drug-induced pulmonary arterial hypertension (D-PAH).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abe K, Toba M, Alzoubi A, Ito M, Fagan KA, Cool CD, Voelkel NF, McMurtry IF, Oka M. Formation of plexiform lesions in experimental severe pulmonary arterial hypertension. Circulation 121: 2747–2754, 2010. doi:10.1161/CIRCULATIONAHA.109.927681. - DOI - PubMed
    1. Abenhaim L, Moride Y, Brenot F, Rich S, Benichou J, Kurz X, Higenbottam T, Oakley C, Wouters E, Aubier M, Simonneau G, Bégaud B; International Primary Pulmonary Hypertension Study Group . Appetite-suppressant drugs and the risk of primary pulmonary hypertension. N Engl J Med 335: 609–616, 1996. doi:10.1056/NEJM199608293350901. - DOI - PubMed
    1. Al-Husseini A, Kraskauskas D, Mezzaroma E, Nordio A, Farkas D, Drake JI, Abbate A, Felty Q, Voelkel NF. Vascular endothelial growth factor receptor 3 signaling contributes to angioobliterative pulmonary hypertension. Pulm Circ 5: 101–116, 2015. doi:10.1086/679704. - DOI - PMC - PubMed
    1. Anderson IM, Tomenson BM. The efficacy of selective serotonin re-uptake inhibitors in depression: a meta-analysis of studies against tricyclic antidepressants. J Psychopharmacol 8: 238–249, 1994. doi:10.1177/026988119400800407. - DOI - PubMed
    1. Andrade SE, McPhillips H, Loren D, Raebel MA, Lane K, Livingston J, Boudreau DM, Smith DH, Davis RL, Willy ME, Platt R. Antidepressant medication use and risk of persistent pulmonary hypertension of the newborn. Pharmacoepidemiol Drug Saf 18: 246–252, 2009. doi:10.1002/pds.1710. - DOI - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources