[PMID]: | 27712113 |
[Au] Autor: | Erlendson MJ; D'Arcy N; Encisco EM; Yu JJ; Rincon-Cruz L; Peltz G; Clark JD; Chu LF |
[Ad] Endereço: | a Department of Anesthesia , Stanford University School of Medicine , Stanford , CA , USA. |
[Ti] Título: | Palonosetron and hydroxyzine pre-treatment reduces the objective signs of experimentally-induced acute opioid withdrawal in humans: a double-blinded, randomized, placebo-controlled crossover study. |
[So] Source: | Am J Drug Alcohol Abuse;43(1):78-86, 2017 Jan. |
[Is] ISSN: | 1097-9891 |
[Cp] País de publicação: | England |
[La] Idioma: | eng |
[Ab] Resumo: | BACKGROUND: Treatments for reducing opioid withdrawal are limited and prone to problematic side effects. Laboratory studies, clinical observations, and limited human trial data suggest 5-HT3-receptor antagonists and antihistamines may be effective. OBJECTIVES: This double-blind, crossover, placebo-controlled study employing an acute physical dependence model evaluated whether (i) treatment with a 5-HT3-receptor antagonist (palonosetron) would reduce opioid withdrawal symptoms, and (ii) co-administration of an antihistamine (hydroxyzine) would enhance any treatment effect. METHODS: At timepoint T = 0, healthy (non-opioid dependent, non-substance abuser) male volunteers (N = 10) were pre-treated with either a) placebo, b) palonosetron IV (0.75 mg), or c) palonosetron IV (0.75 mg) and hydroxyzine PO (100 mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10 mg/70kg). At T = 165, 10 mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. RESULTS: Comparison of average baseline OOWS scores with OOWS scores obtained 15 minutes after naloxone was significant (p = 0.0001). Scores from 15 minutes post-naloxone infusion showed significant differences in OOWS scores between treatment groups: placebo, 3.7 ± 2.4; palonosetron, 1.5 ± 0.97; and palonosetron with hydroxyzine, 0.2 ± 0.1333. CONCLUSIONS: Pretreatment with palonosetron significantly reduced many signs of experimentally-induced opioid withdrawal. Co-administration with hydroxyzine further reduced opioid withdrawal severity. These results suggest that 5-HT3 receptor antagonists, alone or in combination with an antihistamine, may be useful in the treatment of opioid withdrawal. |
[Mh] Termos MeSH primário: |
Hidroxizina/uso terapêutico Isoquinolinas/uso terapêutico Quinuclidinas/uso terapêutico Síndrome de Abstinência a Substâncias/tratamento farmacológico
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[Mh] Termos MeSH secundário: |
Estudos Cross-Over Método Duplo-Cego Sinergismo Farmacológico Voluntários Saudáveis Seres Humanos Masculino Morfina/efeitos adversos Morfina/antagonistas & inibidores Naloxona/farmacologia Adulto Jovem
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL |
[Nm] Nome de substância:
| 0 (Isoquinolines); 0 (Quinuclidines); 30S50YM8OG (Hydroxyzine); 36B82AMQ7N (Naloxone); 5D06587D6R (palonosetron); 76I7G6D29C (Morphine) |
[Em] Mês de entrada: | 1711 |
[Cu] Atualização por classe: | 171113 |
[Lr] Data última revisão:
| 171113 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 161008 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1080/00952990.2016.1210614 |
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