Pharmacokinetic-Pharmacodynamic Correlations of Antihistamines
Hartmut Derendorf, Günther Hochhaus in Handbook of Pharmacokinetic/Pharmacodynamic Correlation, 2019
In another study by Simons et al.,58 the pharmacokinetics and pharmacodynamics of hydroxyzine were investigated in nine elderly subjects after a single oral dose of 0.7 mg/kg. Serum concentrations of the active metabolite cetirizine were also measured in this study. In the elderly, the terminal half-life was prolonged and the volume of distribution was enlarged. In addition, hydroxyzine and cetirizine had the same elimination half-life. The mean wheal and flare areas were significantly suppressed from 1 to 144 h. The suppressive effect on wheal and flare was extremely prolonged. Eight out of nine subjects fell asleep between 2 and 6 h postdosing, which coincided with the time of the peak serum concentration of hydroxyzine, which occurred earlier than that of cetirizine.
Generalized Anxiety Disorder
Stephen M. Stahl, Bret A. Moore in Anxiety Disorders: A Guide for Integrating Psychopharmacology and Psychotherapy, 2013
In their Cochrane Review, Guaiana, Barbui, and Cipriani (2010) describe the results of five randomized controlled studies that compared this antihistamine to either placebo or another anxiolytic. Hydroxyzine was comparable to BZDs and buspirone in terms of efficacy, acceptability, and tolerability, although it was associated with more sleepiness or drowsiness. In one study, for example (Boerner, Garziella, & Achenbach, 2007), a total of 299 patients with GAD were administered an average of 45 mg/day for 4 weeks in an open ambulant study. The HAM-A score dropped significantly from 25.5 to 10.4. After 1 month, 61.5& of the patients had responded, and 42.2& reached remission. It was stated that even other types of anxiety symptoms were also reduced, such as phobic and panic attacks, and that even some depressive symptoms were improved.
Chronic pain in children
Peter R Wilson, Paul J Watson, Jennifer A Haythornthwaite, Troels S Jensen in Clinical Pain Management, 2008
The goal of acute therapy is to abort an attack of severe pain and suppress pain, nausea, and vomiting. For mild-moderate pain and minimal nausea, preferred agents are NSAIDs and paracetamol. For severe pain, opioids may be judiciously used, as well as nasal sumatriptan.103[II] As previously noted, we have little pediatric data regarding the safety and efficacy of subcutaneous sumatriptan and oral triptans.104[II] Adverse effects of the 5–HT 1B/1D receptor agonists include initial selective constriction of intracranial extracerebral vessels and inhibition of release of vasoactive neuropeptides from trigeminal nerve terminals in the intracranial vessels and meninges. Secondary effects include inhibition of nociceptive neurotransmission in the brain stem and cervical spinal descending trigeminal sensory nucleus.105 For nausea and vomiting, diphenhydramine and hydroxyzine are least associated with adverse effects, such as the mood changes and dystonia potentially seen with chlorpromazine and metoclopramide. The dosing regimens shown in Table 44.3 are suggested for pediatric dosing.
Comment on: Are antimuscarinic effects common in hydroxyzine overdose? A cohort analysis of antimuscarinic effects in hydroxyzine and diphenhydramine poisoned patient
Published in Clinical Toxicology, 2023
Samantha S. Klein, Joshua Bloom, Marlis Gnirke, Mary Ann Howland
As the authors point out, diphenhydramine has more potent antimuscarinic activity and has resulted in significant morbidity, critical care admissions, and mortality in the USA when compared to hydroxyzine. This medication is available without a prescription and can easily be obtained in large bottles of hundreds of pills for self-harm or misuse [2,3]. Patients who overdose on hydroxyzine, as the authors point out, typically have more favorable outcomes. The most common manifestation of toxicity is central nervous system depression without other sequelae seen in diphenhydramine overdose, such as antimuscarinic toxicity, seizures, or ventricular dysrhythmias from sodium channel blockade. Interestingly, hydroxyzine is only available by prescription and thus is less accessible than diphenhydramine. Lack of access to large doses may have driven the results observed by the authors, and reporting the range of diphenhydramine recorded doses would have been useful in this regard.
An international Delphi study on the burden of allergic rhinoconjunctivitis and urticaria and the role of bilastine among current treatment options
Published in Expert Review of Clinical Immunology, 2023
MK Church, GW Canonica, P Kuna, M Maurer, R Mösges, Z Novak, NG Papadopoulos, P Rodriguez del Rio
The fact that some, albeit few experts were undecided on this statement may reflect that most clinicians, who manage allergic rhinitis and urticaria, do not assess sleep stages in their patients and therefore cannot be certain that impairing effects of first-generation antihistamines are due to specific effects on sleep. On the other hand, there is still a widespread belief that sleep is aided by adding a sedating first-generation H1-antihistamine, as hydroxyzine, at night, although this is not supported by available data [47]. Moreover, with a terminal half-life of 20–25 h [48], hydroxyzine has hangover effects into the next day, with a negative impact on overall performance [47]. Similarly, the first-generation antihistamine chlorpheniramine has shown to cause a significant worsening of next day cognitive functioning and psychomotor performance, whereas a single nocturnal dose of fexofenadine has advantages over chlorpheniramine, demonstrating to be free of disruption of nighttime sleep and detrimental effects on cognitive performance the next day [49]. Further information on the effects of antihistamines on sleep and sensory-motor performance may be a good target for further analysis.
Safety of cetirizine in pregnancy
Published in Journal of Obstetrics and Gynaecology, 2018
Amanda Golembesky, Maureen Cooney, Rossen Boev, Anne-Françoise Schlit, Jürgen W. G. Bentz
This study summarises data from 49 prospectively reported pregnancies exposed to CTZ. Its results support the expectation that exposure to CTZ in pregnant women is not linked to adverse effects and outcomes and are in line with those from previous reports. Prospective, observational studies of 39 (Einarson et al. 1997) and 196 (Weber-Schoendorfer and Schaefer 2008) pregnant women exposed to CTZ during the first trimester, respectively, concluded that use of CTZ in early pregnancy does not appear to be associated with increased rates of adverse pregnancy outcomes. Similarly, data from the Swedish Medical Birth Registry, which included 917 women who had taken CTZ during their pregnancy, showed no association with malformations or adverse delivery outcomes, compared to the general population (Källén 2002). A cohort study involving 78 pregnant women exposed to CTZ in the first, and 56 in the second or third trimester demonstrated no increased risk of major malformations or spontaneous abortions when CTZ was taken during organogenesis, compared to the control group of women taking non-teratogenic agents (Etwel et al. 2014). Similarly, a meta-analysis of 10 studies involving 1293 pregnant women reported no increased risk of major malformations or other adverse foetal outcomes following hydroxyzine or CTZ exposure, compared to the unexposed controls (Etwel et al. 2014).
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