Vomiting: a physiological response to acidosis?

Valeur, Jørgen; Julsrud, Joar

doi:10.3109/00365521.2013.825926

Cited by 9 publications

(10 citation statements)

References 6 publications

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“…To avoid these challenges, veverimer removes acid through the GI tract, thus reducing the overall acid accumulation that is the hallmark of chronic metabolic acidosis, and in so doing introduces bicarbonate into the circulation without the addition of deleterious counterions. This mechanism of acid removal has similarities to the physiologic response to prolonged vomiting, chloride-losing diarrhea, or nasogastric suction, each of which removes HCl from the stomach and leads to a rapid increase in serum bicarbonate levels that may result in hypochloremic metabolic alkalosis (Kassirer and Schwartz, 1966;Niv and Fraser, 2002;Khanna and Kurtzman, 2006;Valeur and Julsrud, 2013). It is fundamentally different from these responses in persons with normal kidney function, however, in that veverimer only binds HCl and does not induce the loss of fluid, sodium, and potassium that are hallmarks of hypochloremic metabolic alkalosis (Khanna and Kurtzman, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Acid binding and removal through the gastrointestinal (GI) tract using an amine-based nonabsorbed polymer, resulting in an increase in serum bicarbonate, is a novel approach to treat metabolic acidosis without introducing deleterious counterions (e.g., sodium or potassium) or attempting long-term dietary changes. This approach mimics the physiologic response to acid removal observed in patients with persistent vomiting or during nasogastric suction, each of which results in an elevated serum bicarbonate level (Khanna and Kurtzman, 2006;Gennari and Weise, 2008;Valeur and Julsrud, 2013). The polymer restores the ability to excrete acid from the body, a function that is impaired during chronic kidney disease.…”

Section: Downloaded Frommentioning

confidence: 99%

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Mechanism of Action of Veverimer: A Novel, Orally Administered, Nonabsorbed, Counterion-Free, Hydrochloric Acid Binder under Development for the Treatment of Metabolic Acidosis in Chronic Kidney Disease

Klaerner¹,

Shao²,

Biyani³

et al. 2020

J Pharmacol Exp Ther

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Current management of metabolic acidosis in patients with chronic kidney disease (CKD) relies on dietary intervention to reduce daily endogenous acid production or neutralization of retained acid with oral alkali (sodium bicarbonate, sodium citrate). Veverimer is being developed as a novel oral treatment for metabolic acidosis through removal of intestinal acid, resulting in an increase in serum bicarbonate. Veverimer is a free-amine polymer that combines high capacity and selectivity to bind and remove hydrochloric acid (HCl) from the gastrointestinal (GI) tract. In vitro studies demonstrated that veverimer had a binding capacity of 10.7 ± 0.4 mmol HCl per gram of polymer with significant binding capacity (> 5 mmol/g) across the range of pH values found in the human GI tract (1.5 to 7). Upon protonation, veverimer bound chloride with high specificity, but showed little or no binding of phosphate, citrate or taurocholate (< 1.5 mmol/g), all anions commonly found in the human GI tract. Administration of veverimer to rats with adenine-induced CKD and metabolic acidosis resulted in a significant increase in fecal chloride excretion and a dose-dependent increase in serum bicarbonate to within the normal range, compared to untreated controls. Absorption, distribution, metabolism and excretion studies in rats and dogs dosed with 14 C-labeled veverimer showed that the polymer was not absorbed from the GI tract and was quantitatively eliminated in the feces. Acid removal by veverimer, an orally administered, non-absorbed polymer, may provide a potential new treatment for metabolic acidosis in patients with CKD.

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Section: Discussionmentioning

confidence: 99%

Section: Downloaded Frommentioning

confidence: 99%

Mechanism of Action of Veverimer: A Novel, Orally Administered, Nonabsorbed, Counterion-Free, Hydrochloric Acid Binder under Development for the Treatment of Metabolic Acidosis in Chronic Kidney Disease

Klaerner¹,

Shao²,

Biyani³

et al. 2020

J Pharmacol Exp Ther

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“…The average post-exercise pH was 0.05 lower in BIC than in PL (7.23 ± 0.02 vs. 7.18 ± 0.01, respectively). Following a performance predominantly relying on anaerobic glycolysis, systemic acidosis may cause vomiting as a physiological response to drain H + and thereby allow the stomach to add bicarbonate to the body [35]. Despite the GI problems in PL, we assume that this did not affect performance, as the participants with higher GI distress exhibited similar maximal [La -], RPE and performance compared to participants with minimal GI symptoms.…”

Section: Discussionmentioning

confidence: 99%

Effect of Stacked Sodium Bicarbonate Loading on Repeated All-out Exercise

et al. 2019

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The purpose of this study was to evaluate whether NaHCO3, administered via a 9-h stacked loading protocol (i.e. repeated supplementation with small doses in order to obtain a gradual increase in blood [HCO3 -]), has an ergogenic effect on repeated all-out exercise. Twelve physically active males were randomly assigned to receive either NaHCO3 (BIC) or placebo (PL) in a double-blind cross-over design. NaHCO3 supplementation was divided in three identical 3-h cycles: a 6.3 g bolus at the start, followed by 2.1 g doses at +1-h and +2-h, yielding a total NaHCO3 intake of 0.4 g·kg−1 BM over 9-h. At the end of each cycle, participants performed 2-min all-out cycling. Capillary blood samples were analyzed for [HCO3 -], pH and [La-]. Pre-exercise blood [HCO3 -] in PL decreased from 25.6±0.2 mmol·L−1 in bout 1 to 23.6±0.2 mmol·L−1 in bout 4, while increasing from 25.5±0.2 to 31.2±0.4 mmol·L−1 in BIC (P<0.05). Concomitantly, pre-exercise pH values gradually decreased in PL (from 7.41±0.00 to 7.39±0.01) and increased in BIC (from 7.41±0.01 to 7.47±0.01; P<0.05). Mean power output of the four bouts was higher in BIC (428±20 W) than in PL (420±20 W; P<0.05). The ergogenic effect on repeated all-out exercise occurred in the absence of gastrointestinal distress.

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“…High lactate levels can be a trigger for recurrent vomiting, which can contribute to thiamine deficiency, thus MELAS may be a risk factor for WE. 14 – 16 …”

Section: Discussionmentioning

confidence: 99%

“…High lactate levels can be a trigger for recurrent vomiting, which can contribute to thiamine deficiency, thus MELAS may be a risk factor for WE. [14][15][16] Originally, WE was associated with thiamine deficiency due to chronic alcoholism, malnutrition and malabsorption. More recently, several researches suggest a correlation between mitochondrial dysfunction, lactic acidosis as well as oxidative stress leading to selective loss of certain neurons.…”

Section: Discussionmentioning

confidence: 99%

Wernicke–Korsakoff syndrome associated with mtDNA disease

Jimoh

Sebe

Balicza

et al. 2020

Ther Adv Neurol Disord

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Introduction: Wernicke encephalopathy (WE) and Wernicke–Korsakoff syndrome (WKS) are well-known disorders caused by thiamine deficiency. In addition to the classical concept of these diseases, some literature data suggest a connection between mitochondrial dysfunction and WE/WKS. Psychotic disorders and WKS seem to run in families, as the deficiency of the oxidative phosphorylation can be a trigger factor in psychotic events and WE/WKS as well. We present a patient harbouring the m.A3243G mtDNA mutation with the clinical and magnetic resonance imaging (MRI) findings of WKS who developed schizophrenia with predominantly negative symptoms some years later. Case presentation: A 27-year-old woman was referred to our clinic with severe weight loss after severe vomiting episodes, memory dysfunction and gait ataxia. Family history, as well as clinical, imaging and laboratory findings suggested a mitochondrial aetiology of her symptoms. Brain MRI detected bilateral mild thalamic lesions and loss of corpus mammillae, indicating Wernicke encephalopathy. Genetic testing detected an m.A3243G mtDNA mutation, which has been frequently associated with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes. High-dose vitamin B1 supplementation with supportive antioxidant therapy improved the patient’s memory and learning disturbance; however, some months later she developed psychosis with predominantly negative symptoms and her cognitive functions deteriorated again. Both cognitive and negative symptoms responded well to cariprazine monotherapy. Discussion: Mitochondrial disease due to mtDNA alteration can be a rare cause of WE. In addition to vitamin B1 supplementation, cariprazine with significant dopamine D3 receptor binding can be useful to treat the predominantly negative symptoms and cognitive dysfunction in patients with mitochondrial dysfunction. Conclusion: We assume that patients with a mitochondrial disorder might be prone to develop WE/WKS and therefore need tailored supportive therapy during metabolic crisis as well as symptom-based personalized antipsychotic treatment.

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Vomiting: a physiological response to acidosis?

Cited by 9 publications

References 6 publications

Mechanism of Action of Veverimer: A Novel, Orally Administered, Nonabsorbed, Counterion-Free, Hydrochloric Acid Binder under Development for the Treatment of Metabolic Acidosis in Chronic Kidney Disease

Mechanism of Action of Veverimer: A Novel, Orally Administered, Nonabsorbed, Counterion-Free, Hydrochloric Acid Binder under Development for the Treatment of Metabolic Acidosis in Chronic Kidney Disease

Effect of Stacked Sodium Bicarbonate Loading on Repeated All-out Exercise

Wernicke–Korsakoff syndrome associated with mtDNA disease

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