Ion.Altered NET Activity and AtomoxetineThe improved HR in response to atomoxetine seen within this study is consistent with the growing evidence that decreased expression or activity of NET is involved within the pathophysiology of POTS.33,34 If reduced NET activity is present in some individuals with POTS, then a further decrease in NET activity (such as with NRI medicines) could exacerbate the signs and symptoms of POTS. This model aligns with our studyDOI: 10.1161/JAHA.113.Study LimitationsDetailed sympathetic nervous method assessments had been not MEK Inhibitor review performed before and following atomoxetine administration in thisJournal of your American Heart AssociationNET Inhibition in POTSGreen et alORIGINAL RESEARCHstudy. Assessments of sympathetic nerve targeted traffic and plasma norepinephrine levels may support to improved understand the physiological responses observed within this trial. Further, this was an acute study, and longer-term research are necessary to assess chronic tolerability and clinical utility of NRIs in POTS.11. Kaplan G, Newcorn JH. Pharmacotherapy for kid and adolescent attention-deficit hyperactivity disorder. Pediatr Clin North Am. 2011;58:9920, xi. 12. Grubb BP. Postural tachycardia syndrome. Circulation. 2008;117:2814817. 13. Kanjwal K, Saeed B, Karabin B, Kanjwal Y, Grubb BP. Use of methylphenidate in the treatment of patients struggling with refractory postural tachycardia syndrome. Am J Ther. 2012;19:2. 14. Kelly RP, Yeo KP, Teng CH, Smith BP, Lowe S, Quickly D, Read HA, Smart SD. Hemodynamic effects of acute administration of atomoxetine and methylphenidate. J Clin Pharmacol. 2005;45:85155.ConclusionsNET inhibition with atomoxetine acutely enhanced standing HR and worsened symptom burden in sufferers with POTS. This suggests that NRIs are poorly tolerated in sufferers with POTS and should be administered with caution.15. Wernicke JF, Faries D, Girod D, Brown J, Gao H, Kelsey D, Quintana H, Lipetz R, Michelson D, Heiligenstein J. Cardiovascular effects of atomoxetine in kids, adolescents, and adults. Drug Saf. 2003;26:72940. 16. Schroeder C, Birkenfeld AL, Mayer AF, Tank J, Diedrich A, Luft FC, Jordan J. Norepinephrine transporter inhibition prevents tilt-induced pre-syncope. J Am Coll Cardiol. 2006;48:51622. 17. Monarch Pharmaceuticals I. Florinef acetate fludrocortisone acetate tablet solution label. Day-to-day Med NIH Gov 2011. http://dailymed.nlm.nih.gov/dailymed/ archives/fdaDrugInfo.cfmarchiveid=71912 (δ Opioid Receptor/DOR Antagonist Species accessed July 7, 2012). 18. Jacob G, Shannon JR, Black B, Biaggioni I, Mosqueda-Garcia R, Robertson RM, Robertson D. Effects of volume loading and pressor agents in idiopathic orthostatic tachycardia. Circulation. 1997;96:57580. 19. Raj SR, Black BK, Biaggioni I, Harris PA, Robertson D. Acetylcholinesterase inhibition improves tachycardia in postural tachycardia syndrome. Circulation. 2005;111:2734740. 20. Coffin ST, Black BK, Biaggioni I, Paranjape SY, Orozco C, Black PW, Dupont WD, Robertson D, Raj SR. Desmopressin acutely decreases tachycardia and improves symptoms inside the postural tachycardia syndrome. Heart Rhythm. 2012;9:1484490. 21. Dupont WD, Plummer WD Jr. Power and sample size calculations. A critique and laptop system. Control Clin Trials. 1990;11:11628. 22. Witcher JW, Lengthy A, Smith B, Sauer JM, Heilgenstein J, Wilens T, Spencer T, Biederman J. Atomoxetine pharmacokinetics in young children and adolescents with consideration deficit hyperactivity disorder. J Youngster Adolesc Psychopharmacol. 2003;13:533. 23. Wong DT, Threlkeld PG, Very best KL, Bymaster FP.
