肌肉和静脉注射痛力克术后镇痛效果的观察

痛力克是作用于外周的非麻醉性、非甾体类抗炎剂，通过抑制外周或中枢的前列腺素合成起镇痛作用。作者对６０例（两组各３０例）ＡＳＡⅠ～Ⅱ级择期手术患者在术后回病房切口微痛时，肌肉和静脉单次注射等效剂量痛力克３０ｍｇ，观察镇痛总有效率均为１００％，显效率分别为６６．７％和７０％，起效时间为１８±４．５和１５±３．４ｍｉｎ，完全镇痛时间为９０５±６２０．０３和５６３±４３９．５９ｍｉｎ。认为肌肉注射不受客观条件限制，使用方便可靠，为首选方法     

Central effect of Ketorolac involving NMDA receptors activity

Possible central mechanisms underlying the analgesic action of Ketorolac, a non-steroidal antiinflammatory drug (NSAID) have been investigated using an iontophoretic approach. We found that the excitation induced by N-methyl- -aspartate (NMDA) on spinal wide dynamic range (WDR) neurons was prevented, or reduced, by Ketorolac applied before or after the start of the NMDA ejection. The data suggest that Ketorolac can achieve its central analgesic effect by interfering with the NMDA receptor activity on the spinal neurons.     

断指再植术后3种镇痛方法的临床效果观察比较

目的探索断指再植术后最佳镇痛方法。方法选择断指再植手术75例,随机分成3组。每组25例,A组:自控式镇痛泵;B组:酮咯酸氨丁三醇30mg,im,tid;C组:静脉滴注盐酸哌替啶100mg加入500mL 0.9%NS中持续缓慢滴注。视疼痛情况调节滴速。结果 A组镇痛效果最佳,好于B组、C组(P<0.05),C组费用最低。结论断指再植术后使用自控式镇痛泵的镇痛效果优于其他2组术后镇痛方法。     

Hesperidin produces antinociceptive response and synergistic interaction with ketorolac in an arthritic gout-type pain in rats

Hesperidin occurs in greatest concentration in plants from the Rutaceae and Lamiaceae families. In human nutrition it contributes to the integrity of blood vessels and its deficiency in the diet has been linked to abnormal capillary leakiness as well as pain. In this study, the bioflavonoid hesperidin was identified as an active compound in an ethanol extract of the Rosmarinus officinalis aerial parts tested in the pain-induced functional impairment model in the rat (PIFIR) as an assay of inflammatory and chronic nociception similar to that observed in clinical gout. Hesperidin produced a dose-dependent and significant response with an ED₂₅ = 1666.72 mg/kg in comparison to an ED₂₅ = 302.90 mg/kg for the extract or an ED₂₅ = 0.47 mg/kg for the reference drug ketorolac in the PIFIR model. Although the antinociceptive response of R. officinalis was reverted in presence of the opioid antagonist naloxone (10 mg/kg, s.c.) and the 5HT_1A antagonist WAY100635 (0.12 mg/kg, s.c.), the hesperidin response was not modified by naloxone (10 mg/kg), WAY100635 (0.12 mg/kg), bicuculline (1 mg/kg, s.c.), flumazenil (10 mg/kg, i.p.) or caffeine (1 mg/kg, s.c.). Nevertheless, it was reduced in presence of capsazepine (10 or 20 mg/kg, s.c.) suggesting the participation of the TRPV1 receptor, which was reinforced when hesperidin significantly reduced the capsaicin-induced nociceptive response. A synergistic interaction was also observed when antinociceptive doses of hesperidin were combined with those of ketorolac producing 15 combinations mainly in additive and supra-additive responses. These results provide evidence for the antinociceptive activity of hesperidin and demonstrate synergistic response when combined with ketorolac, possibly by involvement of the TRPV1 receptor, suggesting their clinical potential in pain therapy.     

酮咯酸氨丁三醇与氟比洛芬酯用于骨科膝关节周围手术术后镇痛对比观察

目的:对比观察氟比洛芬酯与酮咯酸氨丁三醇用于骨科膝关节周围手术术后镇痛(PCA)的效果。方法:选择膝关节周围下肢手术120例,随机分为两组,各60例。氟比洛芬酯(F)组:氟比洛芬酯250mg,酮咯酸氨丁三醇(T)组:酮咯酸氨丁三醇150mg,两组均用生理盐水稀释到100mL,手术结束前半小时接静脉自控镇痛泵。观察记录时点为术后1、4、8、12、24、48h的静态和动态VAS评分、PCA按压次数、镇痛满意度及不良反应。结果:两组患者术后各时点的静态VAS评分及按压次数比较差异无统计学意义(P>0.05),静态VAS评分均<4分。F组术后8、12、24h的动态VAS评分明显高于T组(P<0.05),恶心、呕吐总发生率高于T组(P<0.05)。结论:与氟比洛芬酯相比,酮咯酸氨丁三醇用于膝关节周围手术术后镇痛效果满意,且不良反应少,是术后镇痛的良好选择。     

酮咯酸氨丁三醇用于腹腔镜胆囊切除术对患者超前镇痛的观察

目的观察酮咯酸氨丁三醇对于腹腔镜胆囊切除术(LC)患者的超前镇痛作用。方法 60例择期行LC患者随机分为T组、R组、C组3组,各20例。T组分别于切皮前30 min缓慢静脉推注酮咯酸氨丁三醇30 mg(0.9%氯化钠溶液稀释至10 ml),手术结束前30 min缓慢静脉推注0.9%氯化钠溶液10 ml;R组切皮前30 min缓慢静脉推注0.9%氯化钠溶液10 ml,手术结束前30 min缓慢静脉推注酮咯酸氨丁三醇30 mg;C组分别于切皮前30 min、手术结束前30 min缓慢静脉推注0.9%氯化钠溶液10 ml。采用视觉模拟量表(VAS)评价3组各时点的疼痛强度,采用Ramsay系统进行术后镇静评分,并观察术后的不良反应。结果在术后30 min、1 h、3 h、6 h,T组和R组的VAS均比C组的低,差异有统计学意义(P<0.05),在其余时点,两组VAS的差异无统计学意义。而T组和R组的VAS的差异无统计学意义(P>0.05),术后C组曲马多用量明显大于T组和R组(P<0.05)。结论酮咯酸氨丁三醇能效缓解腹腔镜手术的术后疼痛,且无明显不良反应,但在LC中超前镇痛的效果与给药时点无明显关系。     

Comparison of cyclooxygenase inhibitory activity and ocular anti-inflammatory effects of ketorolac tromethamine and bromfenac sodium

ABSTRACT

Objective: To compare the cyclooxygenase (COX) activity and anti-inflammatory effects of the nonsteroidal anti-inflammatory drugs (NSAIDs) ketorolac tromethamine (ketorolac) and bromfenac sodium (bromfenac).

Methods: Cyclooxygenase activity and selectivity was determined in vitro by measuring prostaglandin E₂ (PGE₂) production following incubation of varying concentrations of NSAID with human recombinant COX‐1 or COX‐2 and arachidonic acid. Anti-inflammatory effects were evaluated in a rabbit model in which an ocular inflammatory response was induced by intravenous injection of 10?µg/kg lipopolysaccharide (LPS). In study animals, one eye was treated with 50?µL (+/–) ketorolac 0.4% (Acular LS) or bromfenac 0.09% (Xibrom) and the other eye with 50?µL buffered saline. In control animals, both eyes were treated with vehicle. All animals were treated twice: 2 hours and 1 hour before LPS.

Main outcome measures: PGE₂ production in vitro, measured by enzyme immunoassay; fluorescein isothiocyanate (FITC)-dextran leakage into the anterior chamber, measured by fluorophotometry; aqueous PGE₂ levels in vivo, measured by ELISA immunoassay.

Results: Ketorolac was six times more active against COX‐1 (?IC₅₀ = 0.02?µM) than COX‐2 (?IC₅₀ = 0.12?µM) while bromfenac was ≈ 32 times more active against COX‐2 (?IC₅₀ = 0.0066?µM) than COX‐1 (?IC₅₀ = 0.210?µM). In the animal model, both drugs resulted in nearly complete inhibition of FITC-dextran leakage and PGE₂ production in the anterior chamber of treated eyes. There was also a 79% inhibition (?p < 0.001) of FITC-dextran leakage in the contralateral eyes of bromfenac-treated rabbits, and a 22.5% inhibition (not statistically significant) in the contralateral eyes of ketorolac-treated rabbits.

Conclusions: Ketorolac is relatively COX‐1 selective while bromfenac is potently selective for COX‐2 over COX‐1. In the animal model, both ketorolac 0.4% and bromfenac 0.09% demonstrated maximal anti-inflammatory activity in treated eyes. Only bromfenac 0.09% had a significant effect on the contralateral eye, suggesting possible systemic absorption of this drug.     

Development and Evaluation of Nasal Formulations of Ketorolac

Ketorolac tromethamine is a potent non-narcotic analgesic with moderate anti-inflammatory activity. Clinical studies indicate that ketorolac has a single dose efficacy greater than morphine for postoperative pain and has excellent applicability in the emergency treatment of pain. Due to incomplete oral absorption of ketorolac, several approaches have been tried to develop a nonoral formulation in addition to injections, especially for the treatment of migraine headache. The aim of our study was to develop a nasal formulation of ketorolac with a dose equivalent to the oral formulation. A series of spray and lyophilized powder formulations of ketorolac were administered into the nasal cavity of rabbits, and their pharmacokinetics profiles were assessed. The spray and powder formulations were compared through their pharmacokinetics parameters and absolute bioavailability. Drug plasma concentration was determined using solid phase extraction, followed by an HPLC analysis. Nasal spray formulations were significantly better absorbed than powder formulations. A nasal spray formulation of ketorolac tromethamine showed the highest absorption with an absolute bioavailability of 91%. Within 30 min of administration, the plasma concentration was comparable to that resulting from an intravenous injection. The absolute bioavailability of a solution of ketorolac acid was 70%. Apparently, the dissolution of ketorolac acid into the mucous layer limits its absorption. There were no significant differences in absorption between different powder formulations. Even the reduction of particle size from 123 θ m to 63 θ m did not indicate better absorption of ketorolac tromethamine from powder formulations. Interestingly, the absolute bioavailability of ketorolac tromethamine from a powder formulation is only 38%, indicating that the drug may not be totally released from the polymer matrix before it is removed from nasal epithelium by mucociliary clearance.     

Efficacy of topical ketorolac tromethamine 0.4% for control of pain or discomfort associated with cataract surgery

SUMMARY

Objective: To evaluate the efficacy of ketorolac 0.4% ophthalmic solution for control of pain and discomfort associated with cataract surgery.

Methods: This was a single-center, double-masked, randomized, fellow-eye placebo-controlled clinical study of 25 patients (mean age 72?years; 76% female) requiring bilateral cataract surgery. Patients received either ketorolac tromethamine 0.4% ophthalmic solution (Acular LS*) or placebo, 1 drop QID for 3?days prior to and 1?day following phacoemulsification and intraocular lens implantation on their first eye, and the other treatment for surgery on the second, fellow eye 1?week–4?weeks later. The physician rated patient cooperation and ocular pain or discomfort during surgery, and patients rated ocular pain or discomfort immediately and 24?h after surgery.

Results: Patients reported significantly less ocular pain during the 24?h following surgery when treated with ketorolac 0.4% than with placebo (?p = 0.02). Ocular pain was reported for only a single ketorolac 0.4%-treated eye (4%) during that period, compared with 39% of placebo-treated eyes (?p = 0.004). No significant differences between eyes treated with ketorolac 0.4% and placebo were observed in patient cooperation, and ocular pain or discomfort during or immediately after surgery. No adverse events occurred during the study.

Limitations: Evaluation of pain is subjective, and the severity of pain experienced in the control, vehicle-treated eyes was low.

Conclusions: The reduction in pain associated with cataract surgery afforded by ophthalmic ketorolac 0.4%, together with its favorable safety profile, make it an important tool to help surgeons meet the high expectations of today's cataract and refractive surgery patients.     

酮咯酸氨丁三醇与曲马多对小儿七氟醚全麻术后躁动的影响

目的观察酮咯酸氨丁三醇与曲马多对小儿七氟醚全麻术后躁动的影响。方法选择全麻下行扁桃体和腺样体切除术的患儿80例,年龄2⁷岁、ASAⅠ7岁、ASAⅠ^Ⅱ级。根据手术结束前静脉注入的药物分为4组,每组20例,曲马多组(T组,手术结束前30 min静注曲马多1 mg/kg),酮咯酸氨丁三醇组(K组,手术结束前30 min静注酮咯酸氨丁三醇0.5 mg/kg),曲马多+酮咯酸氨丁三醇组(T+K组,手术结束前30 min静注曲马多1mg/kg和酮咯酸氨丁三醇0.5 mg/kg),对照组(C组,手术结束前30 min静注盐水5 mL)。记录各组手术时间、术后拔管时间,拔管后5 min(T5)、10 min(T10)的躁动评分,入PACU后记录疼痛和镇静评分,以及术后恶心呕吐的情况。结果各组间患儿手术时间、拔管时间比较差异无统计学意义(P>0.05);T5和T10 2个时点的躁动发生率排序:C组>T组>T+K组,C组>K组>T+K组,差异有统计学意义(P<0.05)。K组躁动发生率高于T组,但差异无统计学意义(P>0.05);入PACU后患儿疼痛评分排序:C组>T组>T+K组,C组>K组>T+K组,差异有统计学意义(P<0.05)。K组疼痛评分高于T组,但差异无统计学意义(P>0.05);术后恶心呕吐发生率T组和T+K组明显高于C组和K组(P<0.05)。结论酮咯酸氨丁三醇和曲马多可减轻术后疼痛,减少小儿七氟醚麻醉后躁动的发生。两种药物联合应用降低术后躁动的效果更显著。