Volume 17: Issue 2

Harrison (Hap) Farber,

Professor of Medicine, Director, Pulmonary Hypertension Center, Boston University/Boston Medical Center, Boston, MA

Editor's Memo

For this issue of Advances, we are examining pulmonary hypertension (PH) associated with drugs and toxins, an increasingly important subgroup of pulmonary arterial hypertension (PAH). This topic is particularly pertinent these days for several reasons: the continuing, and, in many locales, the growing, drug epidemic in the United States; the association of prescribed drugs, such as chemotherapeutic agents and tyrosine kinase inhibitors, with development of PH; and the continued emergence of newer agents, both licit and illicit, that seemingly

The connection between stimulants and pulmonary arterial hypertension (PAH) was first made apparent in the 1960s during an outbreak associated with anorexigen (amphetamine-like appetite suppressants) use. Since then, a total of 16 drugs and toxins have been linked to PAH (ie, drug and toxin-associated PAH [DT-APAH]), including illicit stimulants like methamphetamine. Recently, basic science research and novel genomic studies have started to shed light on possible pathologic and genetic mechanisms implicated in disease development, namely loss of function variants in genes involved in drug detoxification. This review will discuss the history and current state of knowledge regarding stimulants and their association with PAH. It will also discuss clinical management of patients with DT-APAH. Lastly, it will highlight the importance of ongoing research efforts to identify susceptibility factors implicated in DT-APAH and the need for increased pharmacovigilance and awareness to identify new drugs that may be risk factors for PAH. Ultimately, this may be our best strategy to improve clinical outcomes and prevent deadly future outbreaks of DT-APAH.

Pulmonary arterial hypertension (PAH) is a serious, chronic, progressive cardiopulmonary disease. PAH is associated with several concomitant conditions, as well as drugs and toxins.1 2 Methamphetamine abuse is likely associated with the development of PAH.3 Methamphetamine abuse is epidemic in the United States and abroad, with rates of new users escalating since 2012. There are over 100,000 new users annually as young as 12 years old. Treating a patient with a history of methamphetamine abuse poses many challenges for a clinician, including nonadherence, therapeutic treatment selection, complex psychosocial issues, and relapse or continued drug abuse. Patients with methamphetamine-associated PAH (Meth-APAH) have higher mortality rates when compared to idiopathic PAH.3 Having a better understanding of the complexities of addiction and working with a multidisciplinary team that includes a social worker to provide care and counseling to these patients can improve their trajectory. In this article, we will offer insight and background into methamphetamine abuse and addiction, as well as discuss a practical approach for clinicians in treating a patient with Meth-APAH, based on the literature, as well as our personal experiences at University of California, San Francisco Medical Center.

Diet pills such as aminorex, fenfluramine, and dexfenfluramine have been strongly associated with the development of pulmonary arterial hypertension (PAH). Other drugs ostensibly related in function have also been implicated as “likely” associated, including amphetamine, methamphetamine, and the serotonin precursor L-tryptophan. Serotonin signaling is thought to be a mediator of diet pill–associated PAH, and it is also thought to potentially play a significant role in PAH in general. In this article, we review the evidence supporting the serotonin hypothesis in PAH in both contexts, and the potential concerns related to selective serotonin reuptake inhibitors and other medications acting on serotonin signaling pathways.

Memos

Editor's Memo

Stimulants and Pulmonary Arterial Hypertension: An Update

Managing the Patient With Pulmonary Arterial Hypertension and Methamphetamine Use: A Practical Perspective for the Clinician

Anorexigen-Associated Pulmonary Arterial Hypertension and the Serotonin Hypothesis: A Story Worth Telling

Tyrosine Kinase Inhibitor–Induced Pulmonary Arterial Hypertension

PH Professional Network: Drug-Drug Interactions: Treatment Considerations for Pulmonary Hypertension Patients With Human Immunodeficiency Virus and/or Hepatitis C

PH Roundtable: Pulmonary Hypertension Roundtable: Clinical Experiences With Drug- and Toxin-Related PH

Ask the Expert: How Can I Best Provide Care to My Incarcerated Patient With Pulmonary Hypertension?

Conference Abstracts

Guest Editor’s Memo

A Roundtable Discussion Addressing Patient-Centered Care and Quality of Life in Patients With Pulmonary Arterial Hypertension

Editor’s Memo

Pulmonary Hypertension Associated With Parenchymal Lung Disease