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Evaluation and management of syncope and related disorders in the elderly
Published in Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich, Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
Andrea Ungar, Martina Rafanelli, Michele Brignole
Droxidopa is an orally administered artificial amino acid converted both peripherally and centrally into norepinephrine. The enzyme responsible for the conversion, aromatic amino acid decarboxylase, is widely expressed; thus, administration of droxidopa increases norepinephrine even if postganglionic sympathetic neurons are not intact. The drug has received accelerated Food and Drug Administration (FDA) approval for the treatment of symptomatic OH. It has been recently demonstrated that droxidopa improved symptoms and their impact on daily activities, with an associated increase in standing SBP in patients with symptomatic OH due to different orthostatic intolerance syndromes, without worsening supine hypertension (93).
Postural orthostatic tachycardia syndrome: pathophysiology, management, and experimental therapies
Published in Expert Opinion on Investigational Drugs, 2022
Bharat Narasimhan, Devika Aggarwal, Priyanka Satish, Bharat Kantharia, Wilbert S. Aronow
With increasing recognition and growing interest in this condition, a number of new therapies with varying efficacy have emerged over the past decade (Table 3). Droxidopa is an orally administered precursor of norepinephrine that has been approved for symptomatic neurogenic orthostatic hypotension [65]. However, a retrospective study of patients with POTS taking droxidopa demonstrated a modest improvement in symptoms and reported a high rate of discontinuation due to side effects [66]. Desmopressin, a synthetic analogue of the antidiuretic hormone vasopressin, expands circulating blood volume, thereby leading to a significant reduction in standing heart rate in patients with POTS [67]. Care with frequency and dosing is advised due to the risk of headaches, edema, and hyponatremia. Small case series and retrospective studies have shown improvement in symptoms of POTS with erythropoietin therapy [68,69]. This may be explained by the increase in red blood cell volume and its added vasoconstrictive effect. However, its use is limited by its high cost and risk of serious thromboembolic events like stroke and myocardial infarction [10].
State-of-the-art pharmacotherapy for autonomic dysfunction in Parkinson’s disease
Published in Expert Opinion on Pharmacotherapy, 2020
Cecilia Quarracino, Matilde Otero-Losada, Francisco Capani, Santiago Pérez-Lloret
Its efficacy in PD patients was demonstrated in post hoc analysis or the integrated analysis of the 4-phase III trials [38–40]. Biaggioni, et al [38] studied the response of patients with PD, multiple system atrophy, and others, all with neurogenic OH, to droxidopa withdrawal in a multinational, randomized, placebo-controlled double-blind trial. Subjective worsening of symptoms was higher in 43 patients in the placebo group compared with 44 patients treated with droxidopa. Almost 60% of treated patients reported mild adverse effects. Kauffman et al. [40] also studied patients with neurogenic OH (with pure autonomic failure, multiple system atrophy, or PD) responsive to droxidopa treatment in a randomized placebo-controlled multicenter trial. After a 7-day wash-out period, the patients were assigned to droxidopa (n = 82), or placebo (n = 80) for 7 days. Subjective improvement in the mean score of the Orthostatic Hypotension Questionnaire and the actual improvement in standing systolic blood pressure were statistically significant in the droxidopa arm. Post-hoc analysis of the results in the PD subgroup did not reach statistical significance likely because of insufficient data (31 and 35 patients in the placebo and droxidopa arms respectively). Adverse events were mild, headache the most frequent (7% of droxidopa treated patients).
Managing autonomic dysfunction in Parkinson’s disease: a review of emerging drugs
Published in Expert Opinion on Emerging Drugs, 2020
Dinkar Kulshreshtha, Jacky Ganguly, Mandar Jog
Droxidopa (L-3-O dihydroxyphenylserine or L-DOPS) is the most recent addition to the current list of medications in managing OH in PD patients. It is approved for managing symptoms related to OH in the USA/Europe but not in Canada. A recent post hoc analysis using the earlier phase 2 clinical trials of Droxidopa in OH was conducted by Hauser et al. In all three trials, patients received 100–600 mg Droxidopa in three divided doses and it was given over periods varying from 3 weeks to 8 weeks in different trials. In all the three studies, droxidopa was associated with significant improvement in blood pressure measurements on standing, OH questionnaire (OHQ) and OH daily activity scale (OHDAS) [64]. The clinical benefits of droxidopa were shown to be related to lower baseline supine plasma norepinephrine levels in OH patients by Palma et al. in their study on 20 nOH patients. Three patients with extremely low supine plasma norepinephrine levels responded to doses as low as 200 mg while six patients with high norepinephrine levels did not respond even to a maximum dose of 600 mg droxidopa. This might be related to denervation supersensitivity and has clinical implications in identifying patients who would respond to droxidopa [69]. The most common adverse effects noted with droxidopa were dizziness, headache and hypertension but overall, the drug was well tolerated with no drug discontinuation in any group [64]. Thus, droxidopa is a promising agent in managing nOH in PD, for at least short-term use till the beneficial effect of the drug over long term use can be supported by further studies.