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      Systemic review: the pathogenesis and pharmacological treatment of hiccups

      1 , 1 , 2 , 3
      Alimentary Pharmacology & Therapeutics
      Wiley

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          Abstract

          Hiccups are familiar to everyone, but remain poorly understood. Acute hiccups can often be terminated by physical manoeuvres. In contrast, persistent and intractable hiccups that continue for days or months are rare, but can be distressing and difficult to treat.

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          Most cited references42

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          Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C.

          Gabapentin and pregabalin are amino acid derivatives of gamma-amino butyric acid that have anticonvulsant, analgesic, and anxiolytic-like properties in animal models. The mechanisms of these effects, however, are not well understood. To ascertain whether these drugs have effects on sensory neurons, we studied their actions on capsaicin-evoked release of the sensory neuropeptides, substance P and calcitonin gene-related peptide from rat spinal cord slices in vitro. Although release of immunoreactive peptides from non-inflamed animals was not altered by either drug, prior in vivo treatment by intraplantar injection of complete Freund's adjuvant enhanced release from spinal tissues in vitro, which was attenuated by gabapentin and pregabalin. These drugs also reduced release of immunoreactive neuropeptides in spinal tissues pretreated in vitro with the protein kinase C activator, phorbol 12,13-dibutyrate. Our results suggest that gabapentin and pregabalin modulate the release of sensory neuropeptides, but only under conditions corresponding to significant inflammation-induced sensitization of the spinal cord.
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            Is Open Access

            Hiccup: Mystery, Nature and Treatment

            Hiccup is the sudden onset of erratic diaphragmatic and intercostal muscle contraction and immediately followed by laryngeal closure. The abrupt air rush into lungs elicits a "hic" sound. Hiccup is usually a self-limited disorder; however, when it is prolonged beyond 48 hours, it is considered persistent whereas episodes longer than 2 months are called intractable. A reflex arc involving peripheral phrenic, vagal and sympathetic pathways and central midbrain modulation is likely responsible for hiccup. Accordingly, any irritant in terms of physical/chemical factors, inflammation, neoplasia invading the arc leads to hiccups. The central causes of hiccup include stroke, space occupying lesions and injury etc, whereas peripheral causes include lesions along the arc such as tumors, myocardial ischemia, herpes infection, gastroesophageal reflux disease and applied instrumentations on human body etc. Besides, various drugs (eg, anti-parkinsonism drugs, anesthetic agents, steroids and chemotherapies etc) are the possible etiology. An effective treatment of persistent hiccup may be established upon the correct diagnosis of lesion responsible for the serious event. The pharmacotherapy of hiccup includes chlorpromazine, gabapentin, baclofen, serotonergic agonists, prokinetics and lidocaine. Non-pharmacological approaches such as nerve blockade, pacing, acupuncture and measures to hold breathing are also successful. Finally, alternative medicines and remedies are convenient to treat hiccups with uncertain effect. In conclusions, hiccup is likely to result from lesions involving the hiccup reflex arc. The lesion may need to be localized correctly for ablative treatment in patients with intractable hiccup. Apart from lesion ablation, drugs acting on reflex arc may be effective, while some other conventional measures may also be tried.
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              Cardiac safety concerns for domperidone, an antiemetic and prokinetic, and galactogogue medicine.

              Domperidone is a dopamine D2-receptor antagonist developed as an antiemetic and prokinetic agent. Oral domperidone is not approved in the United States, but it is used in many countries to treat nausea and vomiting, gastroparesis and as a galactogogue (to promote lactation). The US Food and Drug Administration (FDA) have issued a warning about the cardiac safety of domperidone.
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                Author and article information

                Journal
                Alimentary Pharmacology & Therapeutics
                Aliment Pharmacol Ther
                Wiley
                02692813
                November 2015
                November 2015
                August 25 2015
                : 42
                : 9
                : 1037-1050
                Affiliations
                [1 ]Division of Internal Medicine; University Hospital Zürich; Zürich Switzerland
                [2 ]Division of Gastroenterology and Hepatology; University Hospital Zürich; Zürich Switzerland
                [3 ]Zürich Center for Integrated Human Physiology; Zürich Switzerland
                Article
                10.1111/apt.13374
                26307025
                28ba166b-e1e2-46ea-b256-6259094f877e
                © 2015

                http://doi.wiley.com/10.1002/tdm_license_1.1

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