Influence of alpha-adrenoceptor blockade with thymoxamine on changes in pupil diameter and accommodation produced by tropicamide and ephedrine.

In a study in 12 healthy volunteers, local instillation of thymoxamine eye-drops (0.2%) completely reversed the mydriasis produced by ephedrine (5%) but not that produced by ephedrine (5%) together with tropicamide (0.5%). Small but significant changes in accommodation were found with ephedrine and reversed by thymoxamine, suggesting that they were mediated through alpha-adrenoceptor activity. The thymoxamine eyedrops were well tolerated.     

Reversal of tropicamide-induced mydriasis by thymoxamine eye drops

In a study in 12 healthy volunteers, local instillation of thymoxamine eye drops (0.5%), completely reversed the mydriasis produced by tropicamide (0.5%), but only incompletely that by tropicamide (1.0%). The difference between these effects was statistically significant (p less than 0.025). The thymoxamine eye drops were well tolerated.     

Comparison of blockade at α-adrenoceptors by thymoxamine and phentolamine in peripheral arteries and veins of man

1. The antagonism at alpha-adrenoceptors by thymoxamine and phentolamine of the response to noradrenaline was investigated in the limb veins and arteries of man.2. Brachial artery infusions of thymoxamine (40 mug/min) produced rises in resting arterial flow of up to 100%. When infused mixed with noradrenaline, thymoxamine (40 mug/min) attenuated the blood flow response to noradrenaline. Blockade was of a similar degree to that which occurred following a 10 min infusion of phentolamine (40 mug/min).3. Local intravenous infusion of thymoxamine (400-2,000 ng/min) mixed with noradrenaline attenuated the venoconstrictor response to noradrenaline. The degree of attenuation was similar to that seen after a 10 min infusion of phentolamine (500 ng/min). Blockade after thymoxamine did not last longer than 16 minutes. Neither thymoxamine nor phentolamine altered resting venous compliance.4. Local intravenous infusions of thymoxamine (500 ng/min) and phentolamine (500 ng/min) abolished the sympathetically mediated venoconstriction produced by overbreathing.5. Systemic injection of thymoxamine (0.1 mg/kg) did not block the reduction in forearm arterial flow produced by locally infused noradrenaline. In two out of three experiments, however, it produced some antagonism of noradrenaline induced venoconstriction. Systemic phentolamine (5 mg) blocked the effect of noradrenaline in the arterial bed, but antagonized its actions in the veins in only one out of three experiments.     

升压药物预注射对全凭静脉麻醉下腹部手术患者升压反应性和术后恢复的影响

目的 探讨全凭静脉麻醉下腹部手术中预注射不同升压药物对患者升压反应性、手术指标、不良反应指标、脑电双频指数(bispectral index,BIS)及复苏时间的影响。方法 选择中国人民解放军联勤保障部队第九八八医院择期行下腹部手术患者300例,按照不同预注射药物分为生理盐水组、麻黄碱组、去氧肾上腺素组,各100例,所有患者均行全凭静脉麻醉。记录麻醉诱导前(T0)、注射药物后1 min(T1)、注射药物后3 min(T2)、注射药物后5 min(T3)、注射药物后7 min(T4)、注射药物后9 min(T5)时患者收缩压(systolic blood pressure,SBP)、舒张压(diastolic blood pressure,DBP)、平均动脉压(mean arterial pressure,MAP)、心率(heart rate,HR)、心输出量(cardiac output,CO)、外周血管阻力(systemic vascular resistence,SVR)、每搏量变异度(stroke volume variation,SVV)等血流动力学指标;记录患者术中低血压、高...     

Effect of thymoxamine in the relief of pain and rate of healing in ischaemic leg ulceration

Summary

A small uncontrolled pilot study was carried out in 6 patients with ischaemic leg ulceration in which pain was severe to assess the effectiveness of thymoxamine in the relief of pain and on the rate of healing. Patients were treated for 3 days with intravenous injections of 0.1?mg thymoxamine/kg body weight and then with oral 40?mg thymoxamine 4-times daily for a further month. The results showed that there appeared to be a definite improvement in pain during intravenous therapy and this was maintained to a large extent, although not so definite, on oral therapy. No enhanced rate of healing, however, was evident.     

The effect of isoprenaline on adrenoceptors in human saphenous vein

1. The order of potency of sympathomimetic amines in causing contraction of strips of human saphenous vein was (-)-adrenaline>(-)-noradrenaline>(-)-phenylephrine>(+/-)-isoprenaline.2. The competitive alpha-adrenoceptor blocking drugs tolazoline, phentolamine, and thymoxamine and the irreversible blocking drug phenoxybenzamine all blocked noradrenaline and isoprenaline contractions.3. Contractions produced by 5-hydroxytryptamine were also blocked by phentolamine and thymoxamine. Fenfluramine-induced contractions were not blocked by thymoxamine or phenoxybenzamine.4. ED50 contracting doses of isoprenaline did not cause consistent relaxation of noradrenaline-contracted strips.5. It is concluded that human saphenous vein contains a dominant population of alpha-adrenoceptors which can be stimulated by high doses of isoprenaline, but the occurrence of beta-adrenoceptors mediating relaxation is rare.     

Ephedrine: a postsynaptic depressant drug at the mammalian neuromuscular junction

The actions of ephedrine were studied using intracellular recording techniques in guinea pig intercostal muscle fiber. After application of ephedrine (10^?5 ?10^?4 M), miniature end-plate potential (MEPP) amplitude was decreased in a concentration-dependent manner. A greater depression in amplitude of end-plate potentials (EPP) was observed in preparations immobilized with d-tuboeurarine. In addition, ephedrine depressed the transient depolarization produced by iontophoretically applied acetylcholine (ACh).In normal Krebs solution and high Mg²⁺ solution, 10^?4 M ephedrine increased MEPP frequency but did not alter the quantal content of EPPs in high Mg²⁺ blocked muscle. In these preparations, EPP amplitude did not change significantly. These results suggested that in the absence of a postsynaptic receptor blocking agent, a slight presynaptic action of ephedrine may offset the decreased responsiveness of the postsynaptic membrane. In addition, no significant alterations of resting membrane potential or the electrical characteristics of the membrane were recorded.Pretreatment of a mouse phrenic nerve-diaphragm preparation with ephedrine did not protect against the irreversible blockade by α-bungarotoxin. These results suggested that ephedrine may depress ACh potentials, MEPPs, and EPPs in dTc-blocked muscle by acting postsynaptically at a site on or associated with the ACh receptor other than the ACh recognition site.     

The effect of thymoxamine on peripheral blood vessels as monitored by the 133Xe clearance technique

The rate of clearance of intra-articularly administred ¹³³Xe provides an indirect method for the measurement of synovial tissue perfusion. The effect of an intra-articular injection of thymoxamine, and of isoprenaline was to increase the clearance rate whereas the converse was seen with noradrenaline. The prior administration of thymoxamine did not affect the isoprenaline response. In suitable doses, thymoxamine both prevented, and reversed the noradrenaline effect.     

麻黄碱对PC12细胞内BDNF、PSD95和synapsin1表达水平的影响

目的 考察麻黄碱对PC12细胞内的脑源性神经营养因子(BDNF)、突触后致密蛋白95(PSD95)和神经突触素1(synapsin1)表达水平的影响,探讨麻黄碱对PC12细胞毒性的作用机制。方法 通过不同浓度的麻黄碱处理PC12细胞后,采用噻唑蓝试剂(MTT)法测定细胞存活率;采用倒置显微镜观察细胞的形态学变化;采用蛋白印迹(Western blot)法检测BDNF、PSD95和synapsin1的蛋白表达水平。结果 麻黄碱呈浓度依赖性降低PC12细胞活力,其引起PC12细胞死亡的IC₂₅和IC₅₀分别为0.536 mmol和2.8 mmol。随着麻黄碱浓度的升高,PC12细胞体积变小,边界模糊,突触数减少,轴突长度减短;BDNF和PSD95的表达水平明显升高;synapsin1的表达水平有所降低。结论 麻黄碱对PC12细胞的毒性作用机制可能与影响BDNF、PSD95和synapsin1的表达水平有关。     

Alpha-adrenoceptor blocking drugs in asthma

1 The effect of α-adrenoceptor blocking drug, thymoxamine alone and in combination with isoprenaline, was studied on the specific airways conductance (SGaw) in ten patients with extrinsic asthma.

2 Thymoxamine when given together with isoprenaline produced significantly greater increase in SGaw as compared to improvement achieved with isoprenaline alone.

3 It is suggested that the potentiation of isoprenaline induced bronchodilatation by thymoxamine is mediated by increased cyclic AMP formation in the bronchial smooth muscle.

     

Mechanisms underlying mechanical responses to Ephedra herb of isolated rabbit urinary bladder and urethra, a possible stress urinary incontinence therapeutic

To compare the mechanisms underlying mechanical responses to ephedrine and Ephedra herb, a main component of Kakkon-to, in isolated male and female rabbit urinary bladder and urethral strips, responses of isolated strips to the agents were recorded in organ bath systems. Ephedrine and Ephedra herb relaxed the female urinary bladder to the similar extent. These relaxations are reversed to contractions by timolol. In the presence of timolol, ephedrine produced less contraction of urethral strips in the female than those in the male; this contraction was abolished by prazosin. Ephedra herb contracted the female urethra less than that of the male, and the contraction was stronger than that by ephedrine. The contraction caused by Ephedra herb in strips treated with timolol was significantly inhibited by prazosin. The prazosin-resistant contraction of the female urethra was greater than that of the male. Quinacrine, a phospholipase A(2) inhibitor, indomethacin, and AA861, a 5-lipoxygenase inhibitor, inhibited the contraction. The contraction was inhibited by ZK 158252, a leukotriene (LT) B(4)-receptor antagonist. These findings suggest that Ephedra herb contracts the urethra via arachidonic acid metabolites together with alpha(1)-adrenoceptor stimulation. The metabolites produced by 5-lipoxygenase may stimulate LTB(4), but not CysLt(1), receptors. These contractile components induced by Ephedra herb and Kakkon-to might be effective for the treatment of stress urinary incontinence.     

紫外分光光度法测定氯麻滴鼻液的含量

目的 建立氯麻滴鼻液中氯霉素和盐酸麻黄碱的含量测定方法。方法 采用双波长分光光度法消除组分间干扰进行含量测定。结果 方法的线性关系良好，氯霉素平均回收率为100．4％，B5D为0．5％(n＝6)；盐酸麻黄碱平均回收率为99．7％，RSD为1．3％(n=6)。结论 本法简便、快速、准确。     

麻黄碱与总皂苷对豚鼠气管平滑肌松弛的协同作用

目的　探讨麻黄碱与总皂苷在平喘作用方面有无协同作用。方法　将麻黄碱与总皂苷分成麻黄碱 +总皂苷组、总皂苷组和麻黄碱组进行离体豚鼠气管平滑肌松弛作用强度比较。结果　麻黄碱 +总皂苷组直接松弛豚鼠离体气管平滑肌的作用强度是麻黄碱组的 3 5倍 (P <0 0 5 ) ,总皂苷组无作用 (P >0 0 5 )。麻黄碱 +总皂苷组对氨甲酰胆碱(carbamylcholine,CCH)引起气管平滑肌收缩反应的解痉强度与麻黄碱组相同 ,但两者都比总皂苷组强 (P <0 0 5 )。麻黄碱 +总皂苷、麻黄碱和总皂苷组预先处理气管平滑肌均呈浓度依赖抑制CCH收缩反应 ,三者之间的作用强度无差异。结论　总皂苷对麻黄碱在直接松弛气管平滑肌和抑制CCH引起的气管平滑肌收缩方面具有明显的协同作用 ,但在解痉方面的协同作用不明显     

The evaluation of the alpha-adrenoceptor blocking action of indoramin, phentolamine and thymoxamine on the rat and guinea-pig isolated mesenteric vasculature and aortic spiral preparations

The perfused mesenteric vasculature of the rat is a specific, sensitive and stable preparation for the rapid determination of α-adrenoceptor blocking pA₂ values. Both types of pA₂ determination—the direct determination (Schild, 1947) and the Arunlakshana & Schild (1959) analysis—can be made on this tissue. Indoramin, phentolamine and thymoxamine were evaluated and gave respectively α-block pA₂ values of 8m?05, 7m?84 and 6m?47. The pA₂ values made on the rat perfused mesentery were compared with those obtained on the rat aorta (indoramin 7m?68, phentolamine 8m?29, thymoxamine 6m?50), the guinea-pig aorta (indoramin 7m?38, phentolamine 7m?64, thymoxamine 6m?93) and the perfused mesenteric bed of the guinea-pig (indoramin 8m?48, phentolamine 7m?51, thymoxamine 6m?97). Statistical analyses of Kb (dissociation constant) values suggest that indoramin has an additional blocking action on resistance vessels, which is not possessed by phentolamine or thymoxamine.     

紫外分光光度法测定苯海拉明麻黄碱滴鼻液的含量

目的 建立苯海拉明麻黄碱滴鼻液中盐酸苯海拉明和盐酸麻黄碱的含量测定方法。方法 采用双波长分光光度法消除组分间干扰进行含量测定。结果 方法的线性关系良好。盐酸苯海拉明平均回收率为99．0％，RSD为1．29％；盐酸麻黄碱平均回收率为99．7％，RSD为1．32％。结论 本法简便、快速、准确，适宜于医院制剂分析。     

In Vitro and in Vivo Evaluation in Rabbits of a Controlled Release 5-fluorouracil Subconjunctival Implant Based on Poly(D,L-lactide-co-glycolide)

Purpose. To design a controlled release 5-fluorouracil (5-FU) implant to provide prolonged antifibroblast concentrations of 5-FU in the sub-conjunctival tissues but low concentrations of 5-FU in other ocular tissues. Methods. Implants (5 mg; 2.5 mm diameter × 1.2 mm thickness) of 5-FU or 9:1, 8:2, 7:3 5-FU to polymer mass ratios were made by compression. Poly(D,L-lactide-co-glycolide) polymers with 50:50 and 75:25 lactide to glycolide ratios were used. In vitro release characteristics of four types of implants were studied: 5-FU alone (CT), 5-FU/ polymer matrices (MT), coated 5-FU/polymer matrices with a central hole drilled through the matrix and coating (CM1), and with a central hole in the coating (CM2). MT and CM1 (9:1 drug/polymer) were selected for subconjunctival implantation in rabbits. ¹⁴C-5-FU levels in various ocular tissues and retrieved pellets were monitored. Results. First-order release was observed from CT, MT and CM1 implants. Zero-order release profiles were observed from CM2 implants. Drug release was retarded by formulating 5-FU in a matrix comprising poly(D,L-lactide-co-glycolide) which in turn could be modified by the lactide/glycolide ratio of the polymer, the drug to polymer ratio, coating, and hole dimensions. First-order release kinetics were observed for MT and CM1 implants in the in vivo study in rabbits. A correlation between in vitro and in vivo release was established which allowed in vivo release to be predicted from in vitro release data. For CM1, therapeutic tissue concentrations of 35.2 µg/g (conjunctiva) and 17.7µLg/g (sclera) were found at the implantation site up to 200 hours post-implantation. Tracer levels were undetectable in other ocular tissues. Conclusions. The CM1 implant maintained steady antifibroblast levels in target tissues and minimized levels in nontarget tissues.     

Effects on the human central nervous system of two isomers of ephedrine and triprolidine, and their interaction

1 D(-)ephedrine is four times as potent as L(+)pseudoephedrine in producing both tachycardia and a rise in systolic blood pressure. No changes in diastolic blood pressure occurred in 12 subjects with doses of up to D(-)ephedrine (50 mg) and L(+)pseudoephedrine (180 mg).

2 Significant evidence of stimulation of the central nervous system occurred only after D(-)ephedrine in that tapping rates were increased and subjects could reliably detect that they had received an active drug. While mean performance rates in an auditory vigilance test were higher following both ephedrine isomers these changes were not significant.

3 Impairment of both tapping rates and auditory vigilance occurred following triprolidine in another group of 12 subjects. The effect was generally related to dose of antihistamine given and lasted up to 7.25 hours. Subjective effects were reliably recognized by subjects following all treatments containing triprolidine (2.5 mg or more) for up to 4.75 hours. Using analogue lines for self rating the subjective effects following triprolidine indicated both mental and physical impairment differing significantly from scores after lactose and L(+)pseudoephedrine (60 mg).

4 Combination of triprolidine (2.5 mg) and L(+)pseudoephedrine (60 mg) produced effects similar to triprolidine alone on both subjective measures and the auditory vigilance test. It is suggested that these objective tests and subjective scales could be used to measure effects on the central nervous system produced by antihistamines together with similar drugs, and their interaction with other compounds administered concurrently.

     

Reversal of the bronchodilator action of ephedrine during ventilation with carbon dioxide

Ephedrine reduces the bronchoconstrictor effects of histamine, 5-hydroxytryptamine and acetylcholine in guinea-pigs ventilated with air, but during ventilation with 10% carbon dioxide in air, when blood pH is lowered and blood P_CO2 is raised, ephedrine enhances the bronchoconstrictor responses to all three drugs. Pretreatment with monoamine oxidase inhibitors did not affect the bronchodilator actions of ephedrine, but significantly increased its action in enhancing bronchoconstrictor responses during ventilation with 10% carbon dioxide in air. It is suggested that ephedrine sensitizes bronchial smooth muscle to constrictor drugs and this effect is manifested when the bronchodilator action of ephedrine is abolished. The findings suggest a potentially hazardous effect of ephedrine in the treatment of severe asthmatic attacks.     

Loteprednol and tobramycin in combination: a review of their impact on current treatment regimens

Importance of the field: The treatment of ocular inflammation continues to be a challenge. Topical corticosteroids are effective in reducing ocular inflammation but are limited by adverse events including elevation of intraocular pressure, development of cataracts, glaucoma and inhibition of wound healing with associated risk of infection. Loteprednol etabonate (LE) is a unique C-20 ester corticosteroid designed to produce a predictable therapeutic effect with a low incidence of side effects. Zylet^® (LE/T) a combination of LE and tobramycin (T) is indicated for the treatment of steroid-responsive ocular inflammatory conditions in which there exists either superficial bacterial ocular infection or a potential risk of bacterial infection.

Areas covered in this review: The current review of the literature (Medline and the Cochrane Library, 1996 – 2009) examines the safety and efficacy of LE/T in the treatment of ocular inflammation.

What the reader will gain: Studies with either LE or LE/T indicate that LE has a lower risk of IOP elevation compared with C-20 ketone corticosteroids owing to its rapid de-esterification to inactive metabolites. LE also lacks the ability to form Schiff base intermediates with lens proteins, a common first step in cataractogenesis. LE/T was noninferior to dexamethasone 0.1%/tobramycin 0.3% in the treatment of blepharokeratoconjunctivitis.

Take home message: LE/T may be a safer treatment option for ocular inflammation in which there is risk of superficial bacterial infections.     

Evaluation of the effect of thymoxamine solution 0.5% on mydriasis induced by ibopamine solution 1%

Summary The effects of thymoxamine 0.5% solution and of a placebo solution (mannitol) on the mydriasis induced by ibopamine 1% solution were evaluated in 8 healthy volunteers and 12 patients with eye diseases.One drop of ibopamine was instilled into each eye and 30 min later 1 drop of thymoxamine was instilled into one eye and 1 drop of placebo into the contralateral eye. Pupillary diameter was measured before and 30 min after the instillation of ibopamine, immediately before the treatment with thymoxamine and placebo and 30, 60 and 90 min after the instillation of thymoxamine or of placebo.Within 30 min of treatment, ibopamine had produced a statistically and clinically significant mydriatic effect. In eyes treated with thymoxamine, prompt reversal of mydriasis was observed, the baseline diameter being observed within 60 min.No difference in the time-course of the mydriatic effect was detected between healthy subjects and patients. The pupillary response to thymoxamine was not influenced by the colour of the iris. The tolerability of ibopamine and of thymoxamine was good. No local or systemic adverse events were seen or reported.