A prospective randomized double masked controlled clinical trial to determine the efficacy of multiple drop centbucridine as an ocular surface anaesthetic

In this study, the ocular surface anaesthetic and analgesic efficacies of 0.5% and 1% centbucridine both in saline were compared with 4% lignocaine drops in distilled water in normal healthy volunteers divided into three equal groups. In 99 healthy eyes, keeping one eye as an unanaesthetized control, one drop of any of the above three coded drugs was instilled in the contralateral eye, followed by one more drop of the same drug in the same eye after 3 minutes. The oneset of anaesthesia, achievement and duration of peak activity, total duration of action, the depth of analgesia, and period of burning sensation were all noted in this double-masked randomized controlled trial with the various drug solutions. Total peak duration of anaesthetic as well as analgesic effects in the 99 healthy normal eyes were found to be the highest with centbucridine 1%, followed by 4% lignocaine and 0.5% centbucridine respectively.     

Some pharmacological properties of o-methyl-α-propylaminopropionanilide, a new local anaesthetic

The anaesthetic action of o-methyl-α-propylaminopropionanilide (L 67, Astra) has been studied and compared with lignocaine in different in vitro and in vivo tests. Procaine and amethocaine (tetracaine) were also included in several of the comparisons. In nerve block on the isolated frog sciatic nerve L 67 is somewhat less effective than lignocaine. In all in vivo conditions, however, L 67 is quite comparable to lignocaine as to duration, latency and frequency of anaesthesia. As a spinal anaesthetic in rabbits 2 to 4% solutions of L 67 give a longer duration of anaesthesia than lignocaine. Toxicity in mice and rabbits and respiratory and circulatory effects in cats have also been evaluated. L 67 is almost twice as well tolerated as lignocaine. It is concluded that L 67 may prove to be a useful anaesthetic in certain clinical applications.     

An in vitro model for studying the effects of pharmacological agents on human ciliary beat frequency: effects of lignocaine.

1 The effects of lignocaine hydrochloride on ciliary beat frequency (CBF), measured photometrically in vitro, using human epithelium obtained by nasal brushing was studied in 20 healthy subjects. Above lignocaine concentrations of 2.5 x 10(-3) g/ml cilio-inhibition occurred in a dose-dependent manner. Concentrations greater than 2 x 10(-2) g/ml caused ciliostasis. 2 Lignocaine aerosol was sprayed in vivo on the mucosa of one nasal cavity in five healthy subjects and five patients premedicated for bronchoscopy. CBF, measured in vitro in nasal brushings, was not different for treated and untreated sides. 3 Variation of intrinsic CBF with time after nasal brushings were taken was studied in ten normal subjects. No significant change in CBF was found until after 24 h. 4 We conclude that lignocaine hydrochloride, at concentrations three orders of magnitude above drug levels encountered in clinical practice, inhibits human CBF in a dose-dependent manner. Aerosolised lignocaine hydrochloride in doses which produce local nasal mucosal anaesthesia, does not inhibit CBF subsequently measured in vitro. Lignocaine is a suitable local anaesthetic for use at fibreoptic bronchoscopy when samples are being obtained for study of ciliary function. 5 The measurement of CBF in nasal mucosal brushings provides an in vitro model suitable for studying the effects of pharmacological agents on human ciliary activity.     

Acute local irritative effect of (2'R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic

(2"R)-4'-O-Tetrahydropyranyladriamycin hydrochloride (THP), a new antitumor antibiotic, was administered to rabbits at a concentration from 0.02 to 0.5% by instillation, or by intracutaneous, subcutaneous or intramuscular injection to study its local irritative effect. The irritative effect of THP increased with concentration. At a concentration of 0.5%, THP was irritant to the eye, skin and muscle but at a concentration of 0.1% practically no effect was observed. The effect was equal to or lower than that of doxorubicin. An instillation of 0.5% THP caused reversible irritation effect on the eye. Slight conjunctival responses (redness and chemoisis) were observed. Rinsing reduced the irritative effect. Intracutaneous injection of 0.1 ml of 0.5% THP caused well defined, moderate erythema, surface ulceration and dermal necrosis. Cutaneous muscle necrosis also occurred. At a concentration of 0.02%, dermal necrosis and inflammatory cell infiltration were observed. Erythema, as well as muscle necrosis and calcification with giant cell reaction and inflammatory cell infiltration were observed by an intramuscular injection at a concentration of 0.5%. Subcutaneous injection of 0.5% THP showed no irritative effect.     

The local anaesthetic activity of a benzotriazinium salt.

1 The local anaesthetic properties of 2-n-propyl-4-p-tolylamino-1,2,3-benzotriazinium iodide (TnPBI) were compared with those of lignocaine hydrochloride on intact and desheathed sciatic nerves of the frog, on the phrenic nerve-hemidiaphragm preparation of the rat, and by the intradermal wheal test in the guinea-pig. 2 Both TnPBI and lignocaine were more potent on desheathed than on intact sciatic nerves. The potency of TnPBI was affected more than that of lignocaine by the presence of the sheath in intact nerves. 3 Both drugs inhibited conduction in the rat phrenic nerve, as shown by the reduction in twitch tension of the diaphragm elicited by nerve stimulation. TnPBI also caused an initial augmentation of the twitch tension of the diaphragm when applied directly to the muscle. 4 TnPBI was shown to be approximately twice as potent as lignocaine by the guinea-pig intradermal wheal test. 5 These results are discussed in view of the known effects of TnPBI on intracellular calcium storage.     

The effect of entrapment of procaine hydrochloride in liposomes on its local anesthetic action

The study has shown the effect of liposomally entrapped procaine hydrochloride on local anaesthesia and its intensity after intradermal administration. The experiments of anaesthetic infiltration have been carried out on guinea pig skin applying mechanical stimulus. Liposomes were prepared by the shaking method followed by suspending in phosphate buffer pH 7.2, 0.5% methylcellulose in phosphate buffer or 5% glucose solution. The results of the study were compared with those of procaine hydrochloride in analogous solutions. The study has shown significant influence of liposomally entrapped procaine hydrochloride on the prolongation of local anaesthesia and its intensity. It has also been shown that local anaesthesia was influenced by the composition of the solutions in which liposomes were suspended. The longest effect (55 min) has been observed after administration of liposomes in phosphate buffer with methylcellulose.     

Pharmacological and microbiological evaluations of potential new long-acting local anaesthetics.

The results of the preliminary pharmacological and microbiological evaluations of certain new derivatives of dialkylaminoethyl-phenyl-ether hydrochloride, as potential long-acting local anaesthetics, are reported. The guinea pig intradermal wheal test was used for determining the activity and duration of local anaesthesia (WT). These were assayed at concentrations of 0.5% w/v. Lidocaine hydrochloride, 1.0% w/v, was employed as the standard and normal saline, 0.9% w/v, as the control. The compounds showed outstanding activity profiles and duration of action with no apparent signs of both local and systemic side effects. In addition, the results of inhibition of the ciliated protozoan Tetrahymena pyriformis mobility by the aforementioned compounds are presented. A general relationship between the minimum inhibitory concentration (MIC) of these compounds to inhibit mobility of the whole T. pyriformis cells and the duration of anaesthesia was observed. Moreover, derivatives with tertiary or secondary butyl substituents in the benzene ring, irrespective of position or number, were superior to others and showed prolonged duration of anaesthesia and lower MIC. The dependence of both WT and MIC on partition coefficient (log P) of these compounds indicates that in both biological systems the anaesthetics interact strongly with hydrophobic structures of the T. pyriformis cells membrane resulting in fluidisation and loss of ciliary function.     

A comparative study of centbucridine and lidocaine in dental extraction

A randomized double-blind study comparing the efficacy and tolerability of centbucridine (0.5%) with those of lidocaine (2%) as an anaesthetic agent was conducted in the dental outpatient department on patients attending for dental extraction. One hundred and twenty patients were studied. The degree of analgesia attained with centbucridine compared well with that obtained with lidocaine. The compound was well tolerated with no significant changes in the cardiovascular parameters and no serious side-effects.     

复方盐酸左氧氟沙星丁卡因滴眼液的制备及其质量控制

目的:制备复方盐酸左氧氟沙星丁卡因滴眼液,并建立其质量控制方法。方法:选择盐酸左氧氟沙星及盐酸丁卡因为主药制备复方滴眼液,采用反相高效液相色谱法测定其中主药的含量;通过考察性状、可见异物、pH值、渗透压等指标初步确定其质量控制方法,并对其进行稳定性考察。结果:盐酸左氧氟沙星和盐酸丁卡因检测浓度的线性范围分别为15.06～90.36μg·mL-1(r=0.9998)、7.57～45.42μg·mL-(1r=0.9997),平均回收率分别为102.75%(RSD=1.31%)、99.95%(RSD=0.85%)。所得制剂为淡黄色澄明液体,可见异物符合2010年版《中国药典》(二部)附录IG眼用制剂项下的有关规定,pH在4.0～5.0之间,渗透压为0.285～0.310Osmol;样品在高温、高湿、光照条件下放置10d及室温下放置1个月,各项指标均无明显变化。结论:本制剂处方合理,制备工艺简单,稳定性好,含量测定方法简便、准确。     

比较国产与进口复方噻吗洛尔滴眼液对家兔瞳孔和眼压的影响

目的 :比较复方噻吗洛尔国产滴眼液 (含0 .5 %噻吗洛尔和 2 %硝酸毛果芸香碱 )和进口滴眼液 (含 0 .5 %噻吗洛尔和 2 %盐酸毛果芸香碱 )对家兔瞳孔和眼压的影响。方法 :测量正常家兔瞳孔直径变化 ,制备水负荷高眼压兔模型并用压陷式眼压计测量家兔眼压。结果 :国产和进口滴眼液在给药后 15～ 12 0min ,家兔瞳孔明显缩小 ,较对照组眼压明显下降 ,2组间无显著统计差异。结论 :含不同毛果芸香碱盐基的复方噻吗洛尔国产滴眼液与进口滴眼液均具有明显缩瞳和降眼压作用 ,其药理作用强度和作用持续时间无明显差异。     

Comparative trial of mexiletine and lignocaine in the treatment of early ventricular tachyarrhythmias after acute myocardial infarction

The antiarrhythmic effects of intravenously administered lignocaine and mexiletine were compared over a period of 48 hr in a randomized trial on 24 patients who developed ventricular tachyarrhythmias within 48 hr of the onset of acute myocardial infarction. Mexiletine was given as an initial bolus of 200 mg, followed by an infusion of 1 mg/min reduced to 0.5 mg/min after 1 hr. Lignocaine was given as a bolus of 100 mg, followed by an infusion of 3 mg/min reduced to 2 mg/min after 1 hr. Plasma levels of mexiletine, lignocaine, and monoethylglycinexylidide were monitored. The frequency of "complex" ventricular tachyarrhythmias was significantly lower in the mexiletine-treated group. This group of patients also had significantly fewer ventricular extrasystoles than those receiving lignocaine, the difference being most marked during the second 24 hr of treatment. Too few episodes of ventricular fibrillation occurred for statistical comment. The greater efficacy of mexiletine was not associated with increased drug toxicity.     

盐酸丁卡因滴眼液的薄层色谱鉴别和紫外光谱含量测定

盐酸丁长因滴眼液为局部麻醉药，临床常用于测量眼压、角膜异物剔除和眼科手术前表面麻醉等。１９９０年版《中国医院制剂规范》［１］采用以氯仿－乙醇（１∶１）作溶剂，用碱量法测定含量，缺乏专属性，终点变化迟缓。１９９５年版《中国医院制剂规范》（西药制剂）［２］改用永停满定法，用重氨化测定含量，限于仪器条件，目前还难以普及。因此，作者研究了紫外光谱法测定含量和薄层法定性鉴别，便于普及。本法操作简便、快速，定量准确性和定性专属性均好。一、仪器与药品（一）仪器ＵＶ－２６５ＦＷ型紫外可见分光光度计（日本岛津），…     

Block of cardiac sodium channels by amiodarone studied by using Vmax of action potential in single ventricular myocytes.

1. Acute effects of amiodarone on cardiac sodium channels were investigated in ventricular myocytes isolated from guinea-pig hearts, and compared with those of lignocaine. 2. Transmembrane potential was recorded and controlled by whole-cell current-clamp and voltage-clamp respectively through suction pipette electrodes. The maximum upstroke velocity (Vmax) of the action potential was used as a qualitative index of sodium channel availability. 3. In myocytes treated with amiodarone (1 microM) or lignocaine (40 microM), Vmax of reference action potential elicited at 0.03 Hz was decreased by 6-11%, indicating minimal tonic block of sodium channels. 4. Application of a single conditioning depolarization to those myocytes resulted in a significant decrease in Vmax of a subsequent test action potential. The Vmax reduction was enhanced in a single exponential function as the clamp pulse duration was prolonged. Time constants at 0 mV clamp were 25 ms for amiodarone and 122 ms for lignocaine. 5. Vmax recovery of test action potential following a 1000 ms 0 mV clamp was approximated by a dual exponential function. Time constants for the late slow component (tau R) at the resting potential level were 418 ms for amiodarone and 178 ms for lignocaine. tau R values were shortened in a voltage-dependent manner by hyperpolarization during the coupling interval. 6. These findings suggested that amiodarone, like lignocaine, blocks the sodium channel primarily when it is in the inactivated state. Both onset and offset kinetics of the block are very rapid. Such sodium channel blocking characteristics may contribute to its potent antiarrhythmic activity.     

General anaesthetics and field currents in unclamped, unmyelinated axons of rat olfactory cortex.

1. The effects of seven general anaesthetics and one local anaesthetic having a wide range of physical and chemical properties were studied on nerve terminal Na- and K-mediated currents in slices of olfactory cortex. These currents were measured from the groups of fine unmyelinated axons traversing the surface of the olfactory cortex and which give off synapses en passant. The amplitude of the K-current was visualized by depolarizing the axons via an electrode polarization. 2. The anaesthetics tested were ketamine (0.1-2 mM), pentobarbitone (0.1-5 mM), urethane (5-200 mM), halothane (0.5-5 mM), ether (10-200 mM), alphaxalone (0.001-0.05 mM), diisopropylphenol (0.05-0.5 mM) and lignocaine (0.01-0.5 mM). All had depressant effects on the axonal Na-current (at the higher concentrations tested) and on the K-current (at slightly lower concentrations). The apparent lower potency on the Na-current was considered to be due to a masking of effect as a consequence of the reduction in the K-mediated membrane rectification rather than any real difference in the susceptibilities of the Na and K-currents. 3. Some of the depressant effect of pentobarbitone and alphaxalone was gamma-aminobutyric acid (GABA)-mediated as indicated by the reduced potency in the presence of bicuculline. The actions of ketamine and halothane were unaffected by bicuculline. 4. For some anaesthetics these axonal depressant effects might contribute to general anaesthesia, while for other substances the relatively high concentrations necessary would suggest that this mode of action does not produce effective anaesthesia in vivo.     

Diffuse epithelial keratopathy following a single instillation of topical lignocaine: the damaging drop

Toxic corneal epitheliopathies are a known occurrence following chronic use of topical anesthetic agents in ophthalmology. We report two cases of diffuse epithelial keratopathy following a single drop of 4% lignocaine in two diabetic patients scheduled for fundus fluorescein angiography.     

HPLC法测定复方盐酸利多卡因洗液中3组分的含量

目的:建立以高效液相色谱法同时测定复方盐酸利多卡因洗液中3组分含量的方法。方法:色谱柱为C18,流动相为甲醇-水-三乙胺(58∶42∶0.4),用磷酸调pH至3.0,流速为1mL.min-1,检测波长为240nm,进样量为20μL,柱温为22℃～28℃。结果:利多卡因、醋酸氯己定及曲安奈德检测浓度的线性范围分别为369.6～985.6(r=0.9998)、84.0～224.0(r=0.9998)、12.0～32.0μg.mL-1(r=0.9999);平均回收率分别为99.58%(RSD=0.41%)、99.51%(RSD=0.83%)、100.00%(RSD=0.68%)。结论:本方法操作简便、快速、准确、可靠,可用于该制剂的质量控制。     

Ropivacaine: an update of its use in regional anaesthesia

Ropivacaine is a long-acting, enantiomerically pure (S-enantiomer) amide local anaesthetic with a high pKa and low lipid solubility which blocks nerve fibres involved in pain transmission (Adelta and C fibres) to a greater degree than those controlling motor function (Abeta fibres). The drug was less cardiotoxic than equal concentrations of racemic bupivacaine but more so than lidocaine (lignocaine) in vitro and had a significantly higher threshold for CNS toxicity than racemic bupivacaine in healthy volunteers (mean maximum tolerated unbound arterial plasma concentrations were 0.56 and 0.3 mg/L, respectively). Extensive clinical data have shown that epidural ropivacaine 0.2% is effective for the initiation and maintenance of labour analgesia, and provides pain relief after abdominal or orthopaedic surgery especially when given in conjunction with opioids (coadministration with opioids may also allow for lower concentrations of ropivacaine to be used). The drug had efficacy generally similar to that of the same dose of bupivacaine with regard to pain relief but caused less motor blockade at low concentrations. Lumbar epidural administration of 20 to 30ml ropivacaine 0.5% provided anaesthesia of a similar quality to that achieved with bupivacaine 0.5% in women undergoing caesarean section, but the duration of motor blockade was shorter with ropivacaine. For lumbar epidural anaesthesia for lower limb or genitourinary surgery, comparative data suggest that higher concentrations of ropivacaine (0.75 or 1.0%) may be needed to provide the same sensory and motor blockade as bupivacaine 0.5 and 0.75%. In patients about to undergo upper limb surgery, 30 to 40ml ropivacaine 0.5% produced brachial plexus anaesthesia broadly similar to that achieved with equivalent volumes of bupivacaine 0.5%, although the time to onset of sensory block tended to be faster and the duration of motor block shorter with ropivacaine. Ropivacaine had an adverse event profile similar to that of bupivacaine in clinical trials. Several cases of CNS toxicity have been reported after inadvertent intravascular administration of ropivacaine, but only 1 case of cardiovascular toxicity has been reported to date. The outcome of these inadvertent intravascular administrations was favourable. CONCLUSION: Ropivacaine is a well tolerated regional anaesthetic with an efficacy broadly similar to that of bupivacaine. However, it may be a preferred option because of its reduced CNS and cardiotoxic potential and its lower propensity for motor block.     

Modification by hypoxia, hyperkalaemia and acidosis of the cardiac electrophysiological effects of a range of antiarrhythmic drugs.

1. The electrophysiological effects of a series of drugs with Class I antiarrhythmic activity were examined in sheep Purkinje fibres, superfused in vitro with either a normal or hypoxic, hyperkalaemic and acidotic physiological salt solution (PSS). 2. In normal sheep Purkinje fibres, lignocaine, disopyramide, nicainoprol and propranolol all significantly reduced action potential height and the maximum rate of depolarization of phase zero (MRD) and abbreviated the action potential, without modifying resting membrane potential (RMP). 3. Verapamil at the highest concentration studied, 8 microM, significantly reduced MRD with an associated slight membrane depolarization and abbreviated action potential duration measured at 50% repolarization (APD50). 4. Superfusion of sheep Purkinje fibres with a hypoxic, hyperkalaemic and acidotic PSS resulted in marked reductions in resting membrane potential, upstroke and duration of the action potential. 5. In the presence of modified PSS, lignocaine, propranolol and verapamil all reduced MRD to a greater extent than in normal PSS. The effects of nicainoprol on MRD were not affected whereas those of disopyramide were significantly attenuated. 6. Under simulated ischaemic conditions, lignocaine, propranolol and nicainoprol did not produce a concentration-dependent reduction in action potential duration whereas disopyramide and verapamil, respectively, prolonged and abbreviated both APD50 and APD90. 7. The Na+ channel blocking actions of the different subtypes of Class I antiarrhythmic agents studied, as well as their effects on action potential duration, were modified differently by simulated ischaemia.     

Anaesthesia for shock wave therapy in musculoskeletal disorders: a preliminary report

The potential for using external applied energy to rectify or ameliorate musculoskeletal disorders has been explored for decades. A shock wave is a pressure disturbance: tissue effect is cavitation, producing microtrauma or microfracture and haematoma formation, inducing, as to date is thought, increase in vascularization, increased soft callus and faster enchondral ossification. Anaesthesiological interest in this field is focused in non-union or delayed osseous union, joint stiffness or osteochondrosis and femoral head necrosis in adults. Actually, because of the pain associated with high energy extracorporeal shock wave therapy on bones, anaesthesia is necessary, but, since almost all patients have no complaint after treatment, there is no need of postoperative analgesia. Therefore, short duration anaesthetic techniques and agents should be preferred. Loco-regional anaesthesia or general anaesthesia are both suitable to the purpose. Fifty patients have been treated nowadays in our Institution with shock wave therapy needing anaesthesia. 18 patients (36%) received general anaesthesia. Since patient's stay in hospital was expected to be short, short duration agents have been used, avoiding those causing unpleasent side effects, first emesis. We used Propofol or Remifentanil by continuous infusion, titrated to maintain stable haemodynamics and an appropriate level of anaesthesia. The short duration of action of Propofol depends on its rapid elimination, whereas Remifentanil undergoes rapid biotransformation to minimally active metabolites. 32 patients (64%) received regional anaesthesia. We avoided long acting agents or high concentration drugs. Spinal blocks have been performed with 0.5% hyperbaric bupivacaine; brachial plexus blocks, sciatic-femoral blocks and an epidural block have been performed with 0.5-1% xylocaine or 1% mepivacaine. Shock Wave Therapy has been done during a 3-day hospital stay. With suitable anaesthesiological treatment and preparation, almost all patients could be treated as outpatients or with an overnight hospital stay.     

Pharmaceutical investigation of vancomycin hydrochloride eye drops and their topical application to MRSA eye infection]

Two formulations of 0.5% vancomycin hydrochloride (VM) eye drops (VM-B and VM-C eye drops) were prepared by dissolving commercial VM powder for injection with preserved water B (PWB) containing phosphate buffer and preserved water C (PWC) containing only antimicrobial preservative, respectively. The VM-B eye drops have neutral pH (about 6.3), and the VM-C eye drops acidic pH of about 3.5. The pharmaceutical examination of these eye drops was performed regarding its clinical application to MRSA eye infection. In an irritability test using a rabbit's eye, the average number of winks after instillation of one drop of VM-B eye drops was 0.8 times/min and significantly smaller than that of VM-C eye drops (2.0 times/min). In dark storage at 4 degrees C, no change of VM concentration in both eye drops was observed for 25 weeks after preparation and the mean residual concentrations as determined by the HPLC-UV (240 nm) method were constant over 90% for 8 weeks, of the initial concentration. However, the residual VM concentration of VM-B eye drops under a room condition declined to 58% after 4 weeks and 20% after 8 weeks, and VM in light storage at 40 degrees C was not detectable after 8 weeks. The drug concentration of VM-C eye drops declined to 83% after 4 weeks and 74% after 8 weeks under a room condition, and to 46% after 4 weeks and 20% after 8 weeks under light storage at 40 degrees C. Under these storage conditions, the precipitation of VM related crystals was observed in both the eye drops when the residual percentage of VM was lower than 80%. Judging from HPLC chromatograms of a solution of the precipitated crystals, it was suggested that this crystal was degradation products of VM. The VM-B eye drops was applied to a patient with MRSA eye infection, because other medication was not effective. After continuous instillation of a drop per times every hour to both eyes, MRSA in corneal culture turned out negative after one week, and the clinical condition was remarkably improved. On the basis of the result of eye-irritability, VM-B eye drops with neutral pH was suggested to be superior to acidic VM-C eye drops from a safety point of view. It was also indicated that VM-B eye drops can be effectively used for 8 weeks under dark storage at 4 degrees C for MRSA eye infection, which is a useful piece information for the proper usage of the VM eye drops.