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Abnormal Ventilatory Response to Exercise and Metabolic Acidosis in a Patient on Topiramate and Normal PFT FREE TO VIEW

Nayneshkumar Patel, MD; Teodoro Santiago, MD
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UMDNJ-RWJ Medical School, New Brunswick, NJ

Chest. 2013;144(4_MeetingAbstracts):899A. doi:10.1378/chest.1704279
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SESSION TITLE: Miscellaneous Case Report Posters I

SESSION TYPE: Affiliate Case Report Poster

PRESENTED ON: Tuesday, October 29, 2013 at 01:30 PM - 02:30 PM

INTRODUCTION: Increased ventilation during exercise is one of the primary means by which an organism maintains acid-base balance and normoxemia under conditions of augmented metabolic demands. The mechanism for this is unclear.

CASE PRESENTATION: 48 year old nonsmoking female with migraine headaches was evaluated for decreased exercise capacity. She denied any dyspnea, chest tightness or wheezing. Use of albuterol and absence from work caused no improvement. She was taking valsartan, paroxetine and topiramate for 4-5 years. Physical examination revealed BMI of 19.6, normal resting and ambulatory SpO2, and normal lung examination. PFTs showed FEV1 94%, FEV1/FVC 81%, normal TLC and mouth pressures. Radiologic studies and echocardiogram were unremarkable. Incremental cardiopulmonary exercise test at peak exercise (Table1) showed low oxygen pulse and near maximal heart rate, with ventilatory reserve snd no dynamic hyperinflation or bronchoconstriction. ABG results are shown in Table 2.

DISCUSSION: The mechanism for the ventilatory response to exercise is unclear. We speculate that Topiramate, a known carbonic anhydrase (CA) inhibitor contributed to the exercise induced hypercapnia and the absence of ventilatory compensation to metabolic acidosis in this patient with normal lung function. In humans, carbonic anhydrase (CA) type II accounts for 95% of CA activity in the kidney and with the remaining 5% contributed by type IV and type XII (1). CA catalyzes the rapid interconversion of carbon dioxide and water to bicarbonate and proton (or vice versa). This reaction helps loading of CO2 at tissue level and unloading in lung. Due to this enzyme, CO2 crosses the blood brain barrier and affects chemoreceptor response to acidosis. Topiramate weakly and selectively inhibits carbonic anhydrase isoenzymes II, IV, XII which may contribute to its antiepileptic activity and the abnormal exercise response in this patient.

CONCLUSIONS: Carbonic anhydrase inhibition has been shown to reduce VCO2 kinetics during both moderate and heavy-intensity exercise, demonstrating impaired CO2 elimination in the nonsteady state of exercise(2). A number of case reports also showed induction of metabolic acidosis (3). Exercise intolerance in patients on Topiramate might involve blunting of the respiratory response to exercise with resultant hypercapnia and more profound acidosis.

Reference #1: A.J. Esbaugh : The structure and function of carbonic anhydrase isozymes in the respiratory system of vertebrates. Respiratory Physiology & Neurobiology 154 (2006) 185-198

Reference #2: E.R. Swenson : Carbonic anhydrase inhibitors and ventilation: a complex interplay of stimulation and suppression Eur Respir J 1998; 12: 1242-1247

Reference #3: Nasir S. Mirza et al: Metabolic acidosis with topiramate and zonisamide: an assessment of its severity and predictors. Pharmacogenetics and Genomics. 21(5):297-302, May 2011

DISCLOSURE: The following authors have nothing to disclose: Nayneshkumar Patel, Teodoro Santiago

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