Coronavirus Disease2019 (COVID-19) can increase sympathetic nervous system activity by inducing systemic inflammation and a cytokine storm. This can result in elevated blood pressure, increased heart rate, and vasoconstriction. A 67-year-old Black male was admitted to the emergency department with a chief complaint of shortness of breath for 2 days. On examination, he exhibited edema and symmetric palpable pulses in his lower limbs. His electrocardiogram revealed left axis deviation, sinus tachycardia, and ST-segment elevation. Reverse transcription-polymerase chain reaction confirmed COVID-19. Hydralazine (5 mg) was administered intravenously immediately. The patient was re-evaluated after 20 min during his stay in the emergency department. After two 5 mg doses of hydralazine, he developed reflex tachycardia. To control heart rate, IV hydralazine was replaced with oral atenolol (50 mg once daily), a β1-blocker that reduces cardiac output. Subcutaneous enoxaparin 80 mg daily was given to prevent thrombotic complications in hospitalized COVID-19 patients. Acute hypertension and COVID-19-induced hypertensive emergencies in patients with preexisting hypertension are typically associated with a worse prognosis.

Hydralazine is widely used to treat hypertension during pregnancy and has epigenetic effects in cancer therapy. Cryoplatable human hepatocytes showed concentration-dependent increase in DNA damage response (linear trend p = 0.0069) following 24 h hydralazine treatment. DNA repair-deficient UV5 Chinese hamster ovary (CHO) cell lines expressing human CYP1A2 and either NAT2*4 (reference allele) or NAT2*5 (variant allele) were treated with hydralazine for 24 h. CHO cells expressing NAT2*4 showed a higher acetylation rate than those with NAT2*5 (p < 0.001), whereas CHO cell viability did not differ significantly following hydralazine treatment (p > 0.05). Hydralazine caused a concentration-dependent increase in DNA damage response in the un-transfected UV5 CHO cell line, as well as in each of the UV5 CHO cell lines transfected with human CYP1A2 and/or NAT2 alleles. CHO cells with CYP1A2 only showed higher DNA damage response from hydralazine compared to cells with CYP1A2/NAT2*4 or CYP1A2/NAT2*5 (p < 0.05 and p < 0.0001, respectively), and higher in CYP1A2/NAT2*4 versus CYP1A2/NAT2*5 cells (p = 0.0011). Apurinic/apyrimidinic (AP) sites in CHO cells expressing only CYP1A2 were significantly higher than in the un-transfected UV5 CHO cell line (p < 0.01) and higher in CHO cells expressing CYP1A2/NAT2*4 compared to CYP1A2/NAT2*5, but the difference was not significant (p > 0.05). In contrast, ROS levels were reduced following hydralazine treatment in CHO cells with CYP1A2/NAT2*4 and CYP1A2/NAT2*5 (p < 0.001 and p < 0.05, respectively). The results of the current study document DNA damage responses associated with hydralazine in human hepatocytes and CHO cells. The DNA damage response was increased following N-hydroxylation by CYP1A2, which competes with N-acetylation by NAT2.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides are rare disorders characterized by inflammation of small blood vessels, including capillaries, venules, and arterioles. The three main subtypes of primary ANCA-associated vasculitides (i.e., granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis) can present with diverse and nonspecific symptoms, making diagnosis difficult. We report the case of secondary, drug-induced ANCA vasculitis in a female patient who presented with hemoptysis and dyspnea complicated by acute kidney injury and severe anemia. Serologic testing and renal biopsy confirmed the diagnosis of ANCA-associated vasculitis (AAV). Her hospital course was complicated by multiple gastrointestinal bleeds requiring two interventional radiology procedures, first on her gastroduodenal artery and later on her inferior pancreaticoduodenal artery. The patient was treated with cyclophosphamide and plasma exchange during hospitalization and was transitioned to rituximab and intravenous steroids, resulting in an eventual recovery. This case highlights the intricacies of diagnosing AAV and the potential severe, life-threatening complications, such as gastrointestinal hemorrhage. Early recognition and a multidisciplinary approach are critical to evaluate and treat as well as to improve outcomes in patients with this rare but serious condition.

Drug-induced hypertension or hypotension can have significant clinical consequences, yet BP regulation involves complex, multi-level mechanisms, making translational assessment of pressor effects more challenging than for endpoints such as cardiac repolarization (hERG/QT). Current nonclinical BP studies primarily use telemetry in conscious, freely moving non-rodents, enabling continuous high-fidelity hemodynamic monitoring. These models show reasonable concordance with human data, but some translational challenges exist. The Health and Environmental Sciences Institute (HESI) Global Integrative Strategies Working Group (WG) was established to improve nonclinical cardiovascular (CV) safety assessment through more informative, translational preclinical models. After earlier success characterizing drug-induced effects on cardiac contractility, the WG focused on drug-associated blood pressure (BP) changes. Provided here is the importance of nonclinical models in predicting BP changes and associated challenges. A HESI Global multi-site study focused on addressing these gaps is also introduced. The study aimed to evaluate the reproducibility and translatability of the standard telemetered dog model using compounds with well-characterized mechanisms (midodrine, nifedipine, hydralazine, prazosin, milrinone). Early results show consistent hemodynamic profiles across laboratories, with final results published separately, showing utility of this model for BP liability assessment.

Myasthenia gravis (MG) is an autoimmune disease impairing neuromuscular ‎transmission due to antibodies against acetylcholine receptors. Preeclampsia is a ‎pregnancy-specific hypertensive disorder that can lead to seizures and cerebral ‎complications, typically prevented with IV magnesium sulfate.‎ In MG patients, magnesium is contraindicated as it inhibits acetylcholine release, ‎worsening muscle weakness and risking respiratory failure.‎ We present a pregnant MG patient with additional preeclampsia risk factors: nulliparity, ‎age, epilepsy, gestational diabetes and chronic hypertension. Due to limited literature, a tailored protocol ‎was created including instructions to:‎ avoid magnesium; use levetiracetam or diazepam for seizures;‎ control blood pressure with hydralazine; add labetalol if needed; Cesarean only for obstetric reasons and to ensure team awareness and minimize stress.‎ This case emphasizes the need for individualized care in high-risk pregnancies with MG.

Hydralazine is commonly employed as a time-dependent inhibitor of aldehyde oxidase (AO) in human hepatocytes for reaction phenotyping yet profound inter-lot variability in its inhibitory effects has been reported. To date, the exact mechanistic basis for this observation remains unclarified. Recently, it was reported that the time-dependent inhibition of AO by hydralazine could be reversed by glutathione (GSH). The present study integrates these previously independent observations for the first time by investigating whether GSH-dependent reversibility of hydralazine-mediated AO inactivation contributes to this observed variability. The time-dependent inhibition of human liver cytosolic AO elicited by hydralazine was fully reversed by GSH, whereas no protection was observed for erlotinib, a structurally distinct AO time-dependent inhibitor. Consistent with these findings, the apparent inhibitory potency (IC50) of hydralazine in pooled human hepatocytes was intermediate between GSH-free and GSH-supplemented cytosolic systems, while erlotinib exhibited comparable inhibition across all conditions. These results indicate that GSH-reversible AO inactivation by hydralazine contributes to inter-lot inhibition variability in human hepatocytes and highlight a mechanistic limitation of hydralazine as a chemical inhibitor for AO reaction phenotyping in human hepatocytes.

Tranexamic acid (TXA) is an antifibrinolytic drug that inhibits the conversion of plasminogen to plasmin, thereby reducing the enzymatic degradation of fibrin and preserving hemostasis across various surgical fields. Dacryocystorhinostomy (DCR) is a frequently performed surgical procedure to manage nasolacrimal duct obstruction (NLDO), in which intraoperative bleeding remains a significant challenge that may impair visualization and prolong operative time. However, the overall impact of TXA in DCR remains uncertain. This systematic review aimed to examine the current research on the role of TXA in DCR, focusing on its impact on intraoperative bleeding, surgical duration, and surgical field clarity. The systematic review was conducted in compliance with PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. PubMed/MEDLINE, Cochrane, and Google Scholar databases were searched up to March 30, 2025, and randomized controlled trials (RCTs) assessing TXA use in DCR were identified. Studies were screened and selected based on predefined eligibility criteria. Four RCTs involving a total of 286 patients were included. Three studies compared intravenous or topical TXA with normal saline (placebo), and one compared TXA with hydralazine and remifentanil. Two studies, one evaluating intravenous administration and the other topical administration of TXA, demonstrated a statistically significant decrease in both intraoperative hemorrhage and surgical duration. However, one trial reported no significant difference in the assessed outcomes, and the study that compared TXA with alternative agents found greater efficacy with hydralazine and remifentanil. Surgical field clarity and surgeon satisfaction improved with TXA in some cases, but the results were not statistically significant. A low risk of bias was identified in one trial, whereas the remaining studies were judged to raise some concerns, largely attributed to subjective outcome measures. TXA may be effective in reducing intraoperative hemorrhage and surgical time during DCR, with both topical and intravenous routes demonstrating potential benefits. However, the available evidence remains limited due to small sample sizes, variable outcome measures, and subjective assessments. Further research is required to improve the robustness of the evidence and establish the most effective dosing regimens.

Approximately 795,000 people experience new or recurrent strokes in the United States each year; between 10 to 20% of these are spontaneous intracerebral hemorrhages (ICH). Uncontrolled hypertension is not only the most common cause of ICH but also a major risk factor for hematoma expansion. Resistant hypertension, defined as persistently elevated blood pressure despite the use of three or more antihypertensives of different classes, is common in patients with ICH. A long-acting calcium channel blocker, angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), and a thiazide diuretic are generally considered the mainstay for the treatment of resistant hypertension. However, due to the risk of hyponatremia and worsening cerebral edema, thiazide diuretics should be avoided during the first few weeks of ICH. Recent evidence supports the use of a mineralocorticoid receptor antagonist. While resistant hypertension may be idiopathic, a workup of secondary causes should be pursued. Adequate and timely control of elevated blood pressure remains one of the main cornerstones of treatment in patients with ICH. Previous studies have revealed that resistant hypertension in patients with ICH is associated with longer ICU stays, a higher risk of recurrent stroke, and can contribute to renal, cardiac, and neurologic complications. This emphasizes the need for early initiation of oral antihypertensives and adequate blood pressure control at hospital discharge. Landmark studies have shown that early lowering of SBP to 130-150 mm Hg with smooth, sustained BP control is safe and may improve functional outcomes in patients with mild to moderate ICH. After initiating oral antihypertensives with a calcium channel blocker, an ACEi or ARB beta-blocker, and a mineralocorticoid receptor antagonist to maximally tolerated doses, the next line of antihypertensive treatment should be tailored to the patient's co-morbidities, and may include a beta-blocker, central alpha agonist, hydralazine, and minoxidil. In this review, we discuss the epidemiology of resistant hypertension in ICH and its molecular basis, diagnostic workup, and acute and long-term treatment. We present novel mechanisms implicated in hypertensive ICH, including ferroptosis, neuroinflammation, the CNS-gut microbiome axis, and novel therapeutics. We also propose a simple algorithm for the optimal pharmacological management of resistant hypertension in ICH.