Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The first pyrethroid pesticide, allethrin, was identified in 1949. Allethrin and other pyrethroids with a basic cyclopropane carboxylic ester structure are type I pyrethroids. The insecticidal activity of these synthetic pyrethroids was enhanced further by the addition of a cyano group to give alpha-cyano (type II) pyrethroids, such as cypermethrin. The finding of insecticidal activity in a group of phenylacetic 3-phenoxybenzyl esters, which lacked the cyclopropane ring but contained the alpha-cyano group (and hence were type II pyrethroids) led to the development of fenvalerate and related compounds. All pyrethroids can exist as at least four stereoisomers, each with different biological activities. They are marketed as racemic mixtures or as single isomers. In commercial formulations, the activity of pyrethroids is usually enhanced by the addition of a synergist such as piperonyl butoxide, which inhibits metabolic degradation of the active ingredient. Pyrethroids are used widely as insecticides both in the home and commercially, and in medicine for the topical treatment of scabies and headlice. In tropical countries mosquito nets are commonly soaked in solutions of deltamethrin as part of antimalarial strategies. Pyrethroids are some 2250 times more toxic to insects than mammals because insects have increased sodium channel sensitivity, smaller body size and lower body temperature. In addition, mammals are protected by poor dermal absorption and rapid metabolism to non-toxic metabolites. The mechanisms by which pyrethroids alone are toxic are complex and become more complicated when they are co-formulated with either piperonyl butoxide or an organophosphorus insecticide, or both, as these compounds inhibit pyrethroid metabolism. The main effects of pyrethroids are on sodium and chloride channels. Pyrethroids modify the gating characteristics of voltage-sensitive sodium channels to delay their closure. A protracted sodium influx (referred to as a sodium 'tail current') ensues which, if it is sufficiently large and/or long, lowers the action potential threshold and causes repetitive firing; this may be the mechanism causing paraesthesiae. At high pyrethroid concentrations, the sodium tail current may be sufficiently great to prevent further action potential generation and 'conduction block' ensues. Only low pyrethroid concentrations are necessary to modify sensory neurone function. Type II pyrethroids also decrease chloride currents through voltage-dependent chloride channels and this action probably contributes the most to the features of poisoning with type II pyrethroids. At relatively high concentrations, pyrethroids can also act on GABA-gated chloride channels, which may be responsible for the seizures seen with severe type II poisoning. Despite their extensive world-wide use, there are relatively few reports of human pyrethroid poisoning. Less than ten deaths have been reported from ingestion or following occupational exposure. Occupationally, the main route of pyrethroid absorption is through the skin. Inhalation is much less important but increases when pyrethroids are used in confined spaces. The main adverse effect of dermal exposure is paraesthesiae, presumably due to hyperactivity of cutaneous sensory nerve fibres. The face is affected most commonly and the paraesthesiae are exacerbated by sensory stimulation such as heat, sunlight, scratching, sweating or the application of water. Pyrethroid ingestion gives rise within minutes to a sore throat, nausea, vomiting and abdominal pain. There may be mouth ulceration, increased secretions and/or dysphagia. Systemic effects occur 4-48 hours after exposure. Dizziness, headache and fatigue are common, and palpitations, chest tightness and blurred vision less frequent. Coma and convulsions are the principal life-threatening features. Most patients recover within 6 days, although there were seven fatalities among 573 cases in one series and one among 48 cases in another. Management is supportive. As paraesthesiae usually resolve in 12-24 hours, specific treatment is not generally required, although topical application of dl-alpha tocopherol acetate (vitamin E) may reduce their severity.
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PMID:Poisoning due to pyrethroids. 1618 Sep 29

The seas and oceans around Australia harbour numerous venomous jellyfish. Chironex fleckeri, the box jellyfish, is the most lethal causing rapid cardiorespiratory depression and although its venom has been characterised, its toxins remain to be identified. A moderately effective antivenom exists which is also partially effective against another chirodropid, Chiropsalmus sp. Numerous carybdeids, some unidentified, cause less severe illness, including Carybdea rastoni whose toxins CrTX-A and CrTX-B are large proteins. Carukia barnesi, another small carybdeid is one cause of the 'Irukandji' syndrome which includes delayed pain from severe muscle cramping, vomiting, anxiety, restlessness, sweating and prostration, and occasionally severe hypertension and acute cardiac failure. The syndrome is in part caused by release of catecholamines but the cause of heart failure is undefined. The venom contains a sodium channel modulator. Two species of Physalia are present and although one is potentially lethal, has not caused death in Australian waters. Other significant genera of jellyfish include Tamoya, Pelagia, Cyanea, Aurelia and Chyrosaora.
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PMID:Australian venomous jellyfish, envenomation syndromes, toxins and therapy. 1692 89

Pseudohypoaldosteronism type 1 (PHA1) is a rare genetic disease characterized by neonatal renal salt wasting, vomiting, dehydration and failure to thrive. Affected patients present hyponatremia, hyperkalemia, associated with high levels of plasma renin and aldosterone resulting from a renal or systemic resistance to aldosterone. The systemic form of PHA1 results in a severe phenotype, and high doses of salt supplementation are necessary. The symptoms are life-long recurrent. This form is associated with autosomal recessive transmission. Homozygous or compound heterozygous loss of function mutations in the genes coding for the epithelial sodium channel (ENaC) subunities are responsible for this disease. The renal form of PHA1 results in a mild phenotype. Low doses of salt supplementation are required and usually the symptoms remit at the end of the first year of life. Heterozygous loss-of-function mutations in the mineralocorticoid receptor (MR) gene are associated with the renal form of PHA1 in the majority of the affected families but sporadic cases have been reported. In this review the mechanisms of aldosterone action and its effects are discussed. Additionally, clinical and molecular findings of a Brazilian family with the renal form of PHA1 caused by a nonsense mutation (R947X) in the MR gene are presented.
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PMID:[Mineralocorticoid resistance: pseudohypoaldosteronism type 1]. 1754 35

Valproate is one of the most used anti-epileptic drugs. Its common side effects are nausea, vomiting, weight gain, hair loss, tremor, changes in behavior, slowed thinking and impaired liver function. Blood dyscrasias are also relatively frequent and a few studies reported changes in serum immunoglobulin concentrations with valproate treatment. We describe a case of panhypogammaglobulinemia with transient pancytopenia due to valproate. Pancytopenia was recovered after discontinuation of valproate but panhypogammaglobulinemia has been persisting. Intravenous immunoglobulin is being administrated monthly. Previous reports describe that other sodium channel blockers, such as phenytoin and carbamazepine, have been associated with hypogammaglobulinemia. This report also suggests that immunodeficiencies can be caused by valproate.
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PMID:Valproate-induced panhypogammaglobulinemia. 2279 22

Azaspiracid (AZA) poisoning was unknown until 1995 when shellfish harvested in Ireland caused illness manifesting by vomiting and diarrhoea. Further in vivo/vitro studies showed neurotoxicity linked with AZA exposure. However, the biological target of the toxin which will help explain such potent neurological activity is still unknown. A region of Irish coastline was selected and shellfish were sampled and tested for AZA using mass spectrometry. An outbreak was identified in 2010 and samples collected before and after the contamination episode were compared for their metabolite profile using high resolution mass spectrometry. Twenty eight ions were identified at higher concentration in the contaminated samples. Stringent bioinformatic analysis revealed putative identifications for seven compounds including, glutarylcarnitine, a glutaric acid metabolite. Glutaric acid, the parent compound linked with human neurological manifestations was subjected to toxicological investigations but was found to have no specific effect on the sodium channel (as was the case with AZA). However in combination, glutaric acid (1 mM) and azaspiracid (50 nM) inhibited the activity of the sodium channel by over 50%. Glutaric acid was subsequently detected in all shellfish employed in the study. For the first time a viable mechanism for how AZA manifests itself as a toxin is presented.
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PMID:New insights into the causes of human illness due to consumption of azaspiracid contaminated shellfish. 2592 56

Pseudohypoaldosteronism (PHA) type 1 is a rare, heterogeneous disease characterized by hyponatremia and hyperkalemia due to mineralocorticoid resistance. The clinical features of PHA are usually failure to thrive, vomiting, and dehydration in the neonatal period. Heterozygous mutations in the Nuclear receptor subfamily 3, group C, member 2 (NR3C2) gene result in the dominant renal form of PHA type 1. Mutations in the epithelial sodium channel gene result in the more severe, recessive, systemic form of PHA type 1. Here, we describe the clinical and biochemical characteristics of three sporadic cases from two Korean families diagnosed with the renal form of PHA type 1. Mutation analysis of the NR3C2 gene revealed one novel mutation in twin patients and two functional polymorphisms in one patient with unusual clinical symptoms. Our data contribute to a better understanding of the distinct mutations and clinical manifestations of the renal form of PHA type 1.
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PMID:Clinical Manifestation and Molecular Analysis of Three Korean Patients with the Renal Form of Pseudohypoaldosteronism Type 1. 2824 22

The synthetically produced cyclic peptides solnatide (a.k.a. TIP or AP301) and its congener AP318, whose molecular structures mimic the lectin-like domain of human tumor necrosis factor (TNF), have been shown to activate the epithelial sodium channel (ENaC) in various cell- and animal-based studies. Loss-of-ENaC-function leads to a rare, life-threatening, salt-wasting syndrome, pseudohypoaldosteronism type 1B (PHA1B), which presents with failure to thrive, dehydration, low blood pressure, anorexia and vomiting; hyperkalemia, hyponatremia and metabolic acidosis suggest hypoaldosteronism, but plasma aldosterone and renin activity are high. The aim of the present study was to investigate whether the ENaC-activating effect of solnatide and AP318 could rescue loss-of-function phenotype of ENaC carrying mutations at conserved amino acid positions observed to cause PHA1B. The macroscopic Na+ current of all investigated mutants was decreased compared to wild type ENaC when measured in whole-cell patch clamp experiments, and a great variation in the membrane abundance of different mutant ENaCs was observed with Western blotting experiments. However, whatever mechanism leads to loss-of-function of the studied ENaC mutations, the synthetic peptides solnatide and AP318 could restore ENaC function up to or even higher than current levels of wild type ENaC. As therapy of PHA1B is only symptomatic so far, the peptides solnatide and AP318, which directly target ENaC, are promising candidates for the treatment of the channelopathy-caused disease PHA1B.
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PMID:Restoration of Epithelial Sodium Channel Function by Synthetic Peptides in Pseudohypoaldosteronism Type 1B Mutants. 2828 82

From the perspective of the definition of pain, pain can be divided into emotional and sensory components, which originate from potential and actual tissue damage, respectively. The pharmacologic treatment of the emotional pain component includes antianxiety drugs, antidepressants, and antipsychotics. The anti-anxiety drugs have anti-anxious, sedative, and somnolent effects. The antipsychotics are effective in patients with positive symptoms of psychosis. On the other hand, the sensory pain component can be divided into nociceptive and neuropathic pain. Non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are usually applied for somatic and visceral nociceptive pain, respectively; anticonvulsants and antidepressants are administered for the treatment of neuropathic pain with positive and negative symptoms, respectively. The NSAIDs, which inhibit the cyclo-oxygenase pathway, exhibit anti-inflammatory, antipyretic, and analgesic effects; however, they have a therapeutic ceiling. The adverse reactions (ADRs) of the NSAIDs include gastrointestinal problems, generalized edema, and increased bleeding tendency. The opioids, which bind to the opioid receptors, present an analgesic effect only, without anti-inflammatory, antipyretic, or ceiling effects. The ADRs of the opioids start from itching and nausea/vomiting to cardiovascular and respiratory depression, as well as constipation. The anticonvulsants include carbamazepine, related to sodium channel blockade, and gabapentin and pregabalin, related to calcium blockade. The antidepressants show their analgesic actions mainly through inhibiting the reuptake of serotonin or norepinephrine. Most drugs, except NSAIDs, need an updose titration period. The principle of polypharmacy for analgesia in case of mixed components of pain is increasing therapeutic effects while reducing ADRs, based on the origin of the pain.
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PMID:All about pain pharmacology: what pain physicians should know. 3223 11