Dimenhydrinate for prophylaxis of postoperative nausea and vomiting: a meta-analysis of randomized controlled trials

BACKGROUND: Diphenhydramine and its theoclate salt dimenhydrinate are traditional antiemetics still in use. However, so far the quantitative effect of dimenhydrinate in the prophylaxis of postoperative nausea and vomiting (PONV) has not been evaluated systematically. METHODS: Results from randomized controlled trials investigating the efficacy of dimenhydrinate vs. a control to prevent PONV were included in a meta-analysis. Studies were systematically searched through MEDLINE, EMBASE, the Cochrane-Library, manually screening of reference lists of matching review articles and current issues of locally available peer-reviewed anesthesia journals, up to June 2001. The numbers of patients with complete absence of PONV within 6 h and within 48 h after surgery were extracted as the main end point. Pooled relative benefits (RB) and numbers-needed-to-treat (NNT) with their corresponding 95% confidence intervals (CI) were calculated using a random effects model. This quantitative systematic review was performed following the recommendations of the QUORUM statement. In all, 18 trials with 3045 patients were included in the analysis: 1658 patients received a placebo (control) and 1387 patients received dimenhydrinate. RESULTS: The RB to stay completely free of PONV was 1.2 (95% CI: 1.1-1.4) for the early period (NNT = 8; 95% CI: 5-25) and 1.5 (1.3-1.8) for the overall investigated period (NNT = 5; 95% CI: 3-9). CONCLUSION: Dimenhydrinate is a traditional and inexpensive antiemetic with an efficacy that might be considered as clinically relevant. Although in use for a long time, the dose-response, precise estimation of side-effects, optimal time of administration and the benefit of repetitive doses still remain unclear.     

A partial involvement of histamine in ultrasonically nebulized distilled water-induced bronchoconstriction in guinea-pigs

1. Inhalation of ultrasonically nebulized distilled water (UNDW) can induce bronchoconstriction only in asthmatics, but mechanisms of the response are not well known. We recently reported a guinea-pig model of UNDW-induced bronchoconstriction (UNDW-IB) in which UNDW induces bronchoconstriction when UNDW is inhaled 20 min after a challenge with aerosolized ovalbumin (OA) in passively sensitized, anaesthetized and artificially ventilated guinea-pigs.
2. To elucidate the role of histamine in the UNDW-IB, we examined the effects of antihistamines, diphenhydramine hydrochloride (DH) and chlorpheniramine maleate (CP), and measured histamine content in bronchoalveolar lavage fluid (BALF) in the animal model.
3. DH in doses of 0.1, 1.0 and 10 mg kg⁻¹ and CP in doses of 0.01, 0.1 and 1.0 mg kg⁻¹ administered intravenously 15 min after the OA challenge partially reduced the UNDW-IB at 1 and 2 min after the UNDW inhalation in a dose-dependent manner. Histamine content in BALF recovered 10 min after the UNDW inhalation following the OA provocation was significantly increased compared with that after saline inhalation and before the UNDW inhalation following the OA challenge.
4. Intravenous atropine in a dose of 0.5 mg kg⁻¹ or inhaled disodium cromoglycate in concentrations of 1 and 10 mg ml⁻¹ did not alter the UNDW-IB.
5. These results suggest that histamine is involved in part in the UNDW-IB in our animal model.

     

Possible Role of Histamine in Rheumatoid Arthritis

Basophilocytes from patients with rheumatoid arthritis (RA) responded to leukocyte nuclei from normal persons with histamine release; a similar histamine release induced by the nuclear components RNA and DNA has been demonstrated previously. A role of histamine in RA is also supported by the findings of clinical improvement during treatment with H₁ and H₂ antihistamines in six of 12 patients with RA in active phase, whereas four showed definite deterioration.     

抗组胺药对认知功能和执行能力的影响

抗组胺药是治疗过敏性疾病十分有效的药物，其对中枢神经系统的镇静作用主要表现为认知功能和执行能力的下降，因此，对该药治疗指数或益处／风险比值的评估十分重要。笔者将对评估方法及结果加以综述。     

Histamine receptor-subtype affinities,selectivities, and potencies of emedastine,a novel H1-selective antagonist,and other ocularly employed antihistamines

Emedastine, a novel ocular antihistamine, exhibited nanomolar affinity (K_i = 1.26 nM; pK_i = 8.9) for the histamine H₁-receptor and had a markedly lower affinity for histamine H₂-(K_i = 39.8 μM; pK_i = 4.4) and H₃-(K_i = 12.6 μM; pK_i = 4.9) receptor subtypes. Emedastine was the most H₁-selective antagonist tested, being 31,200 and 10,080 times more active at the H₁-receptor than at H₂- and H₃-receptors, respectively. In contrast, while other ocularly employed antihistamines like pyrilamine, ketotifen, levocabastine, antazoline, and pheniramine had relatively high affinities for the H₁-receptor, they exhibited significantly lower H₁-selectivities than emedastine. In general, the H₁-receptor affinities of the compounds compared well with their potencies for antagonizing histamine-induced phosphoinositide (PI) turnover. Emedastine exhibited antagonist potencies (IC₅₀ values) of 1.8, 1.58, and 0.5 nM in human conjunctival epithelial cells, transformed human trabecular meshwork cells, and human corneal fibroblasts, respectively. In conclusion, emedastine is a high affinity and high potency histamine receptor antagonist with a superior H₁-selectivity than other antihistamines tested. Emedastine may therefore be a useful antihistamine for treating symptoms of ocular allergic diseases. © 1994 Wiley-Liss, Inc.     

Efficacy and safety of antihistamines in allergic skin disorders

Background For patients with urticaria, H₁-antihistamines remain the gold standard medical treatment of choice. They act by blocking H₁ receptors on the vascular endothelial cell surface. Newer, non-sedating antihistamines such as loratadine also act to some extent by blocking the release of histamine from mast cells, basophils and human skin tissue. Efficacy All of the newer antihistamines (loratadine, terfenadine, astemizole and cetirizine) have been shown to have comparable efficacy to the classic sedating antihistamines and to be significantly superior to placebo in terms of symptom improvement. Loratadine has been shown to be at least as effective as the other non-sedating agents and cetirizine. Antihistamines also have a potential benefit in the management of patients with atopic dermatitis. In two studies, loratadine was found to be significantly superior to placebo in the reduction of pruritus. Safety In terms of safety, the newer antihistamines have important differences. Cetirizine, for example, causes dose-related sedation and functional impairment compared to placebo. In contrast, loratadine has no such sedative effects. Terfenadine and astemizole have also been shown to be free of sedative effects, but exceeding the recommended dose of either may increase the risk of a serious cardiac arrhythmia, torsades de pointes. Plasma levels of both terfenadine and astemizole may also be increased as a result of interaction with various drugs. In contrast, loratadine has not been shown to induce ECG changes, even at doses of 40 mg o.d. for 90 days.     

A randomized, double-blind, crossover comparison among cetirizine, levocetirizine, and ucb 28557 on histamine-induced cutaneous responses in healthy adult volunteers

BACKGROUND: Cetirizine is a highly efficacious and long-acting second-generation H1-receptor antagonist for the treatment of allergic diseases, such as allergic rhinitis and chronic idiopathic urticaria, in adults and children. Pharmacologic studies have demonstrated that cetirizine, a racemate mixture composed of equal amounts of two enantiomers, does not undergo hepatic metabolism to any significant level. The enantiomers are excreted mainly unchanged, predominantly in the urine and to a lesser extent in the faeces. METHODS: The pharmacologic activity and potency of the two enantiomers of cetirizine in the management of allergic skin conditions were investigated by studying the effect of treatment with 5.0 mg cetirizine; 2.5 mg levocetirizine, the (R)-enantiomer; and 2.5 mg ucb 28557, the (S)-enantiomer, on histamine-induced wheal and flare response in 18 healthy volunteers. Each treatment was administered as a single oral dose in randomized, double-blind, and crossover manner, and the efficacy of treatment was assessed over a period of 32 h, as per cent inhibition of the histamine-induced wheal and flare areas before treatment. Blood and urine samples were collected in a time-dependent manner and analyzed for the total amounts of each study drug, to elucidate their pharmacokinetic profiles. RESULTS: Both cetirizine and levocetirizine caused a marked inhibition of histamine-induced wheal and flare, whereas ucb 28557 was inactive in this model. Inhibition of the wheal response observed for cetirizine and levocetirizine was apparent by 1 h after dosage and lasted for mean durations of 24.4 and 28.4 h, respectively. In addition, the response for cetirizine and levocetirizine became maximal by 6 h after treatment, rising to 79.5% and 83.8%. Similarly, cetirizine and levocetirizine also markedly inhibited the histamine-induced flare response. This effect was evident for both drugs by 1 h after dosage and lasted over a mean period of 28.4 and 26.0 h, respectively, for cetirizine and levocetirizine. The inhibitory effect of these compounds on histamine-induced flare response was also maximal by approximately 6 h after dosage, peaking at 88.5%) and 83.6%, respectively. Statistical evaluation showed that cetirizine and levocetirizine were equivalent for maximum inhibition of histamine-induced wheal and flare. However, levocetirizine was found to be superior to cetirizine when area under the curve was compared. In contrast, ucb 28557 was not found to inhibit histamine-induced wheal and flare responses at any time during the study period. Plasma concentrations of levocetirizine were found to be approximately double those of ucb 28557 at 4 and 8 h after dosing, and 50-60% of the drugs were excreted unchanged in urine over a period of 32 h. CONCLUSIONS: The finding that, in this model, levocetirizine 2.5 mg has comparable antihistaminic activity to cetirizine 5 mg, whereas its other enantiomer ucb 28557 has no pharmacodynamic effect, suggests that the antihistaminic properties of cetirizine observed in the management of allergic skin conditions are likely to be attributable to levocetirizine.     

Stanozolol in chronic urticaria: a double blind, placebo controlled trial

H1-type antihistamine drugs are mainstays in the management of chronic urticaria. For patients with refractory, chronic, idiopathic urticaria who have failed to benefit from conventional therapy, other safe therapeutic modalities are required. To evaluate the role of stanozolol as an adjunctive therapeutic agent with H1-antihistamine in refractory chronic idiopathic urticaria, we conducted this study. Fifty-eight patients with chronic refractory urticaria were enrolled in this trial and were randomly assigned to two groups (A and B). Patients in group A received 2 mg stanozolol twice daily along with cetrizine 10 mg daily. Patients in group B received cetrizine 10 mg daily and placebo tablets twice daily. The improvement was monitored by estimation of severity score. Of the 58 patients, 26 in group A and 24 in group B could be evaluated. At the end of 12 weeks, 17 patients in group A showed marked to complete resolution as compared to 7 patients in group B (chi-square p<0.01). The intention to treat analysis p value was a found to be <0.007. There was a highly significant decrease in mean severity score at 12 weeks (p<0.001) in group A patients. The present study demonstrated that stanozolol is an effective and safe adjuvant therapy for treatment of chronic refractory urticaria.     

Common Skin Diseases

This continuation of the discussion of common skin dermatoses includes the diagnosis and treatment of warts, seborrheic dermatitis, rosacea, seborrheic and actinic keratoses, and common skin malignancies. Skin cancers affect innumerable guises and may derive from various tissues. The family physician should be familiar with the more common types and be alert to the possibility of rarer kinds.