Drugs and toxins-associated pulmonary arterial hypertension: lessons learned and challenges ahead

Abstract

Since the identification of the link between pulmonary arterial hypertension (PAH) and exposure to certain drugs and toxins nearly fifty years ago, the expanding landscape of available pharmaceuticals and illicit drugs is further fueling this association. While some causative agents in drugs and toxins associated PAH (D&T-APAH) have been identified, little is known about the exact biology and clinical implications of the disease. In this review, we discuss the historical evidence that links PAH with exposure to anorexinogens, cocaine, and methamphetamines and concentrate on what is known about potential pathogenesis, clinical manifestations, and current management. We conclude that future research should focus on studies looking at clinical outcome and susceptibility factors.

Rationale and design of a screening study to detect schistosomiasis‐associated pulmonary hypertension in Ethiopia and Zambia

“…High altitude (>2500 m) can cause PH, 46 and Addis Ababa is located at 2350 m: we are planning to document location of residence and correlate with altitude. Some Ethiopians use khat, a mild stimulant, 47 which could plausibly contribute to PH risk as other stimulants are likely causative of PH 48 : we will assess and quantify khat usage.…”

DNA Damage and Repair in Pulmonary Arterial Hypertension

“…With relevance to DNA damage, hypoxia is reported to downregulate a cell’s DNA repair machinery, leading to an increased prevalence of genomic damage [ 50 , 51 , 52 , 53 ]. Amphetamines, a potent synthetic neuro-stimulant, reportedly have vasoconstrictive and mutagenic properties in vascular cells [ 54 ]. Further, oxidant injury (caused by a hypoxic environment) enhances their neurotoxic effects, proposing amphetamines as a potent trigger for vasculopathy [ 55 ].…”

“…Further, oxidant injury (caused by a hypoxic environment) enhances their neurotoxic effects, proposing amphetamines as a potent trigger for vasculopathy [ 55 ]. It has been reported that people exposed to amphetamine have a 3-fold higher risk factor for the development of PAH [ 54 ]. To understand the mechanism of amphetamine-associated PAH, Chen and colleagues performed an elaborate translational study in PAECs from drug and toxin-induced PAH patients [ 47 ].…”

Drug abuse and HIV-related pulmonary hypertension

“…Drugs of abuse like morphine/opioids, cocaine and methamphetamine have been described as highly potential second-hit to viral proteins in triggering vascular injury and development of HIV-PAH [97, 98]. Nevertheless, isolated use of stimulants is also known to damage the parenchyma or pulmonary vasculature [26] and a subset of drug-abusing individuals end up developing PAH. In the United States, cocaine is one of the most popular drugs of abuse [99] and is known for its vasoconstrictive properties [100].…”

“…A recent report by Quezada et al [13] discovered that a detectable viral load is independently associated with HIV-PAH diagnosis upon multivariate analysis (OR 3.3; 95% CI, 1.04–10; p=0.04) [13]. Importantly, an independent relationship between PAH and exposure to drugs of abuse has also been established [25, 26]. Patients who abuse illicit drugs, such as stimulants (cocaine, methamphetamine) and opioids (morphine, heroin) are at increased risk for HIV infection; and substance use is known to potentiate the development of HIV-related complications including HIV-PAH.…”