an h1 blocker which produces slight sedation but good anti-motion sickness activity is
Mohammed
Guys, does anyone know the answer?
get an h1 blocker which produces slight sedation but good anti-motion sickness activity is from screen.
Histamine H1 Receptor Antagonist
Histamine H1 Receptor Antagonist
Nonsedating histamine H1 receptor antagonists, such as loratadine, cetirizine, cyproheptadine, and hydroxyzine are used for the treatment of urticaria and angioedema.
From: xPharm: The Comprehensive Pharmacology Reference, 2007
Related terms:
EpinephrineMast CellHistamineChronic UrticariaDiphenhydramineHydroxyzineCetirizineFexofenadineCentral Nervous SystemAnaphylaxis
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Management of Food Allergy and Development of an Anaphylaxis Treatment Plan
Jacqueline Wassenberg, Philippe Eigenmann, in Food Allergy, 2012
H1 antagonists
H1 antagonists can be given if a patient develops mild clinical symptoms such as skin symptoms. However, it needs to be emphasized that H1 antagonists have no proven efficacy in the treatment of anaphylaxis.10 In addition, the administration of H1 antagonists should never delay the administration of epinephrine. Oral forms of H1 antagonists are most often preferred as they are non-sedating and long-lasting. The dose should be adapted to the weight of the patient. Rapid-onset H1 antagonists (diphenhydramine or chlorpheniramine) are also available for intravenous injection, but these two first-generation H1 antagonists have a much higher sedative side effect than the second-generation H1 antagonists. Their use should be limited to situations in which oral treatment is not available.
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Antihistamines: H1- and H2-Blockers
Ali Habibi, Edward T. Riley, in Complications in Anesthesia (Second Edition), 2007
H1-BLOCKERS
H1-receptor antagonists competitively inhibit the interaction of histamine with the H1-receptor, thereby inhibiting the vasodilator effects of histamine and preventing the occurrence of edema, flare, and wheal. H1-antagonists are taken primarily for acute allergies that present as rhinitis, urticaria, congestion, or conjunctivitis. However, H1-receptor antagonists may not oppose histamine-induced allergic bronchoconstriction, anaphylaxis, laryngeal edema, or angioedema. This is probably due to the involvement of other mediators (e.g., leukotriene, platelet-activating factor). H1-antagonists are well absorbed from the gastrointestinal tract, and they are metabolized by the hepatic microsomal P-450 system. Most H1-antagonists induce hepatic microsomal enzymes to facilitate their metabolism. The metabolites, whether active or inactive, are renally excreted.
The newer types of H1-receptor antagonists (second-generation or specific H1-blockers) were designed to eliminate the unwanted central nervous system and anticholinergic side effects of older H1-blockers.
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Hydroxyzine Hydrochloride
Mark G. Papich DVM, MS, DACVCP, in Saunders Handbook of Veterinary Drugs (Fourth Edition), 2016
Pharmacology and mechanism of action
Antihistamine (H1 blocker) of the piperazine class. Like other antihistamines, hydroxyzine acts by blocking the H1 receptor and suppresses inflammatory reactions caused by histamine. The H1 blockers have been used to control pruritus and skin inflammation, rhinorrhea, and airway inflammation. Hydroxyzine also has sedative properties and other calming effects on the CNS that are not related to the antihistamine effects.
Another antihistamine, cetirizine, is an active metabolite of hydroxyzine. In dogs, most of the antihistamine effect of the administration of hydroxyzine is from the formation of cetirizine, which occurs readily after IV and oral administration.
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Histamine and Histamine Antagonists∗
Matthew R. Cooke, Joseph A. GiovannittiJr., in Pharmacology and Therapeutics for Dentistry (Seventh Edition), 2017
Absorption, rate, and excretion
H1 antihistamines are well absorbed after either oral or parenteral administration. The onset of action occurs 15 to 60 minutes after an oral dose. Effects are typically maximal in 1 to 2 hours, with a duration of 4 to 6 hours, although the duration is longer for some agents (see Table 18-2). In contrast, most second-generation H1 antihistamines have a considerably longer duration of action. Loratadine is transformed to an active metabolite with an average elimination half-time of greater than 24 hours, which allows once-daily dosing.
TABLE 18-3. Classification of H1 Receptor Blockers
H1 Receptor Class X Substitution on Antihistamine Molecule
Alkylamines Carbon
Ethanolamines Oxygen
Ethylenediamines Nitrogen
Piperazines Piperazine ring
Phenothiazines Phenothiazine nucleus
Piperidines Piperidine ring
Biotransformation of first-generation H1 antihistamines is terminated by conversion to inactive metabolites through hydroxylation in the liver. Second-generation antihistamines are extensively metabolized in the liver by the CYP3A4 microsomal enzyme. In some cases, such as with loratadine, these result in active metabolites. Concurrent administration of other agents metabolized by this same enzyme can reduce the biotransformation of these particular antihistamines. Other second-generation H1 antihistamines (e.g., acrivastine and cetirizine) are not metabolized to an active form and are largely excreted unchanged in the urine. Cetirizine is a metabolite of the first-generation agent hydroxyzine.
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H1-Blockers
C.M. Groth, N.M. Acquisto, in Encyclopedia of Toxicology (Third Edition), 2014
Antihistamines for motion sickness
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:To assess the effectiveness of antihistamines in the prevention and treatment of motion sickness in adults and children.
Cochrane Database Syst Rev. 2017 Jul; 2017(7): CD012715.
Published online 2017 Jul 7. doi: 10.1002/14651858.CD012715
PMCID: PMC6483357
Antihistamines for motion sickness
Nadine Karrim, Nombulelo Magula, and Yougan Saman
Author information Copyright and License information Disclaimer
This article has been updated. "Antihistamines for motion sickness" in volume 2022, CD012715.Go to:
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To assess the effectiveness of antihistamines in the prevention and treatment of motion sickness in adults and children.
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Background
Description of the condition
Definition
Motion sickness is a syndrome that occurs as a result of passive body movement in response to actual motion, or the illusion of motion when exposed to virtual and moving visual environments. It generally occurs as a physiological response in a healthy person with an intact vestibular system; however, the presentation may be modulated by various pathologies (Bertolini 2016; Murdin 2015).
Presentation
The presentation can include nausea, vomiting, loss of appetite, gastric awareness, increased sensitivity to odours, headaches (including migraines), dizziness, sweating, pallor, sensations of bodily warmth, increased salivation, bradycardia, arterial hypotension, general malaise, repetitive yawning and sopite syndrome (Bertolini 2016; Golding 2015). Space motion sickness differs from general motion sickness and is characterised by sudden projectile vomiting within minutes of weightlessness (Thornton 2013). Symptoms produced by motion sickness may be severe enough to have a negative impact on cognition and performance (Matsangas 2014).
Epidemiology
Historically, motion sickness was first described in seafarers (Hippocrates). A recent study undertaken on expedition ships to Antarctica has shown that motion sickness was the most common reason for consultation, with 150 out of a total of 680 physician consultations for prophylaxis followed by an additional 142 visits (27%, 4.2 per 1000 person‐days) for treatment (Schutz 2014).
Car sickness can affect most people with varying degrees of severity, under the right circumstances (Wada 2015), and is worse in passengers than drivers (Dong 2011). In one study it occurred in 25.9% of experienced rally co‐drivers, while reading and while seated as rear‐seat passengers (Perrin 2013). It may also prove a significant factor in the use of autonomous cars (Diels 2016), and on tilting trains, but can be influenced by compensation strategies (Förstberg 1998). Space motion sickness affects 50% of astronauts within the first 24 to 72 hours of weightlessness (Thornton 2013). Virtual reality has been shown to induce motion sickness (Nishiike 2013), and an incidence of up to 56% has been demonstrated with the use of video games (Stoffregen 2008). Amongst cinema patrons, 54.8% experienced motion sickness after viewing a 3D movie compared to 14.1% after viewing a 2D movie (Solimini 2013).
Motion sickness is rare in children under the age of two, but increases through childhood with a peak incidence at age nine, followed by a progressive decline through adolescence and adulthood (Henriques 2014). There is a slight preponderance in females (Henriques 2014; Paillard 2013; Perrin 2013).
Ménière’s disease and vestibular migraines are associated with increased motion sensitivity (Sharon 2014). A similar association between patients with vestibular migraines and those with migraines without vestibular symptoms has been shown (Murdin 2015). Benign paroxysmal positional vertigo and vestibular neuritis show no association with motion sickness (Golding 2015). Bilateral vestibular failure has a protective effect against the susceptibility to motion sickness, although this is not seen with unilateral vestibular failure (Murdin 2015).
Aetiology/pathophysiology
The sensory conflict or mismatch theory suggests that conflict arises between one's visual, proprioceptive and vestibular systems when the actual motion experienced differs from the anticipated motion (Reason 1978). Oman 1990 suggested that the difference between all the true sensory input and all the expected sensory information results in the conflict vector. The larger this vector, the greater the likelihood and severity of motion sickness. Bles 1998 further postulated that only vertical input is responsible for motion sickness, suggesting an alternate theory known as the subjective vertical conflict theory, while Holly 1996 expanded this to include all translations. Another hypothesis suggests a link between motion sickness and the time constant of velocity storage (Cohen 2003).
A genetic predisposition showed concordance of 70% in childhood and 50% in adulthood in monozygotic and dizygotic twins (Reavley 2006).
Diagnosis
The Reason and Brand Motion Sickness Susceptibility Questionnaire remains the most widely used tool to assess susceptibility to motion sickness (Golding 1998). Once symptoms have been established, Graybiel’s diagnostic criteria may be used to grade the severity of motion sickness (Graybiel 1968). There is no laboratory test that is pathognomonic of motion sickness. Electrogastrography (Cevette 2014), vestibular evoked myogenic potentials (Tal 2013), vestibulo‐ocular reflexes (Tanguy 2008), caloric testing (Sharon 2014), computerised dynamic posturography (Tal 2010), neurochemical markers (ACTH, epinephrine, norepinephrine) (Kohl 1985), and measurements of autonomic activity (Cowings 1986) have all been used to evaluate and study motion sickness.
Frontiers
Motion sickness occurs under a variety of circumstances and is common in the general population. It is usually associated with changes in gastric motility, and hypothermia, which are argued to be surrogate markers for nausea; there are also reports that respiratory function is affected. As laboratory rodents are incapable of vomiting, Suncus murinus was used to model motion sickness and to investigate changes in gastric myoelectric activity (GMA) and temperature homeostasis using radiotelemetry, whilst also simultaneously investigating changes in respiratory function using whole body plethysmography. The anti-emetic potential of the highly selective histamine H1 receptor antagonists, mepyramine (brain penetrant) and cetirizine (non-brain penetrant), along with the muscarinic receptor antagonist, scopolamine, were investigated in the present study. On isolated ileal segments from Suncus murinus, both mepyramine and cetirizine non-competitively antagonized the contractile action of histamine with pKb values of 7.5 and 8.4, respectively; scopolamine competitively antagonized the contractile action of acetylcholine with pA2 of 9.5. In responding animals, motion (1 Hz, 4 cm horizontal displacement, 10 min) increased the percentage of the power of bradygastria, and decreased the percentage power of normogastria whilst also causing hypothermia. Animals also exhibited an increase in respiratory rate and a reduction in tidal volume. Mepyramine (50 mg/kg, i.p.) and scopolamine (10 mg/kg, i.p.), but not cetirizine (10 mg/kg, i.p.), significantly antagonized motion-induced emesis but did not reverse the motion-induced disruptions of GMA, or hypothermia, or effects on respiration. Burst analysis of plethysmographic-derived waveforms showed mepyramine also had increased the inter-retch+vomit frequency, and emetic episode duration. Immunohistochemistry demonstrated that motion alone did not induce c-fos expression in the brain. Paradoxically, mepyramine increased c-fos in brain areas regulating emesis control, and caused hypothermia; it also appeared to cause sedation and reduced the dominant frequency of slow waves. In conclusion, motion-induced emesis was associated with a disruption of GMA, respiration, and hypothermia. Mepyramine was a more efficacious anti-emetic than cetirizine, suggesting an important role of centrally-located H1 receptors. The ability of mepyramine to elevate c-fos provides a new perspective on how H1 receptors are involved in mechanisms of emesis control.
ORIGINAL RESEARCH article
Front. Physiol., 14 June 2017
Sec. Clinical and Translational Physiology
https://doi.org/10.3389/fphys.2017.00412
Brain Activation by H1 Antihistamines Challenges Conventional View of Their Mechanism of Action in Motion Sickness: A Behavioral, c-Fos and Physiological Study in (House Musk Shrew)
Longlong Tu1, Zengbing Lu1, Karolina Dieser2, Christina Schmitt2, Sze Wa Chan3, Man P. Ngan1, Paul L. R. Andrews4, Eugene Nalivaiko5 and John A. Rudd1,6*
1School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
2Department of Informatics and Microsystem Technology, University of Applied Sciences Kaiserslautern, Zweibrücken, Germany
3School of Health Sciences, Caritas Institute of Higher Education, Hong Kong, China
4Division of Biomedical Sciences, St. George's University of London, London, United Kingdom
5School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia
6Brain and Mind Institute, The Chinese University of Hong Kong, Hong Kong, China
Motion sickness occurs under a variety of circumstances and is common in the general population. It is usually associated with changes in gastric motility, and hypothermia, which are argued to be surrogate markers for nausea; there are also reports that respiratory function is affected. As laboratory rodents are incapable of vomiting, was used to model motion sickness and to investigate changes in gastric myoelectric activity (GMA) and temperature homeostasis using radiotelemetry, whilst also simultaneously investigating changes in respiratory function using whole body plethysmography. The anti-emetic potential of the highly selective histamine H1 receptor antagonists, mepyramine (brain penetrant), and cetirizine (non-brain penetrant), along with the muscarinic receptor antagonist, scopolamine, were investigated in the present study. On isolated ileal segments from , both mepyramine and cetirizine non-competitively antagonized the contractile action of histamine with pK values of 7.5 and 8.4, respectively; scopolamine competitively antagonized the contractile action of acetylcholine with pA2 of 9.5. In responding animals, motion (1 Hz, 4 cm horizontal displacement, 10 min) increased the percentage of the power of bradygastria, and decreased the percentage power of normogastria whilst also causing hypothermia. Animals also exhibited an increase in respiratory rate and a reduction in tidal volume. Mepyramine (50 mg/kg, i.p.) and scopolamine (10 mg/kg, i.p.), but not cetirizine (10 mg/kg, i.p.), significantly antagonized motion-induced emesis but did not reverse the motion-induced disruptions of GMA, or hypothermia, or effects on respiration. Burst analysis of plethysmographic-derived waveforms showed mepyramine also had increased the inter-retch+vomit frequency, and emetic episode duration. Immunohistochemistry demonstrated that motion alone did not induce c-fos expression in the brain. Paradoxically, mepyramine increased c-fos in brain areas regulating emesis control, and caused hypothermia; it also appeared to cause sedation and reduced the dominant frequency of slow waves. In conclusion, motion-induced emesis was associated with a disruption of GMA, respiration, and hypothermia. Mepyramine was a more efficacious anti-emetic than cetirizine, suggesting an important role of centrally-located H1 receptors. The ability of mepyramine to elevate c-fos provides a new perspective on how H1 receptors are involved in mechanisms of emesis control.
Introduction
Motion sickness, also known as kinetosis and travel sickness, is a common but complex syndrome which is characterized by a cluster of signs and symptoms including cold sweating, facial pallor, drowsiness, hypersalivation, “stomach awareness”, and nausea and vomiting (Golding and Gresty, 2015). Symptomology is very inter-individual variable (Sharma, 1997; Golding, 2006; Murdin et al., 2011) and there is no standardized method of assessment (Shupak and Gordon, 2006; Murdin et al., 2011). The most widely accepted mechanism of motion sickness is the “sensory-mismatch theory” which proposes motion-generated sensory conflict and neural mismatch between converging vestibular, visual and proprioceptive input patterns, that are different from learned and expected sensory patterns (Reason and Brand, 1975; Reason, 1978); for a discussion of other theories or modifications of the “sensory-mismatch theory” (see Oman, 2012; Oman and Cullen, 2014; Bertolini and Straumann, 2016). Irrespective of how sensory mismatch occurs, our understanding of how conflicted signal activate the pathways responsible for the induction of nausea and vomiting and accompanying physiological response, particularly in the stomach, is not well defined (Yates et al., 2014).
Two main classes of drug, anticholinergics (e.g., scopolamine) and antihistamines (e.g., promethazine) are the most common treatments for motion sickness (Schmäl, 2013; Golding and Gresty, 2015). However, these types of agents are variably efficacious in motion sickness and are associated with unwanted side effects including sedation, drowsiness, blurred vision, depression, and dry mouth/nose/throat (Spinks and Wasiak, 2011; Schmäl, 2013). Furthermore, the efficacy of all existing anti-motion sickness drugs is quite modest. The antihistamines used in humans to treat motion sickness are brain penetrant and are also weak muscarinic receptor antagonists (Simon and Simons, 2008; Schmäl, 2013). Compounds that do not penetrate the blood brain barrier have also been examined for their anti-motion sickness potential in humans. For example, the non-brain penetrant H1 receptor antagonist, terfenadine, possessing affinity for H1 receptor (IC50 = 6 nM) (Benavides et al., 1995), suppressed motion-induced nausea and autonomic dysfunction (Kohl et al., 1991). However, other non-brain penetrant compounds such as cetirizine and fexofenadine (the active metabolite of terfenadine) failed to prevent motion sickness, although their side effect profiles were not documented (Cheung et al., 2003). In these clinical studies, the motion sickness-rating scores were related to “nausea” and not “vomiting.” It remains unknown, therefore, whether highly selective, non-brain penetrant histamine H1 receptor antagonists are able to affect vomiting, as opposed to nausea or associated physiological changes, in the absence of undesirable side effects.
Guys, does anyone know the answer?