Drug- or toxin-induced pulmonary arterial hypertension

Drug- or toxin-induced pulmonary arterial hypertension (PAH) is a form of pulmonary arterial hypertension that develops as a direct consequence of exposure to certain drugs or toxic substances. Classified within Group 1 of the clinical classification of pulmonary hypertension, this condition is characterized by elevated blood pressure in the pulmonary arteries due to progressive narrowing and remodeling of the small pulmonary vessels. The primary body system affected is the pulmonary vasculature, which in turn places significant strain on the right side of the heart. Key symptoms include progressive shortness of breath (dyspnea), fatigue, chest pain, dizziness, syncope (fainting), and peripheral edema (swelling of the ankles and legs). As the disease progresses, right heart failure may develop. Substances historically associated with this condition include anorexigens (appetite suppressants) such as aminorex, fenfluramine, and dexfenfluramine, which carry a definite risk. Other agents with varying levels of association include toxic rapeseed oil, dasatinib, methamphetamines, and certain selective serotonin reuptake inhibitors (SSRIs) when used during pregnancy. The pathological changes in the pulmonary vasculature closely resemble those seen in idiopathic PAH, including medial hypertrophy, intimal fibrosis, and plexiform lesions. Treatment follows the general approach used for other forms of PAH and includes PAH-specific therapies such as endothelin receptor antagonists (e.g., bosentan, ambrisentan), phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil), prostacyclin analogues (e.g., epoprostenol, treprostinil), and soluble guanylate cyclase stimulators (e.g., riociguat). Discontinuation of the offending drug or toxin is a critical first step, though the pulmonary vascular disease may not be fully reversible. Supportive measures include diuretics, oxygen therapy, and in severe cases, lung transplantation may be considered. Prognosis varies depending on the causative agent, the severity of disease at diagnosis, and the response to treatment.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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