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Background: It is known that serious refractory hypotension during anesthesia may develop in some patients treated with antidepressants. However the detail of this phenomenon remains unclear., Methods: We performed a retrospective study based on written anesthesia records from April 2011 through September 2012 (n=5,578). We picked up patients who had received various types of antidepressants. We excluded cases in which neuraxial anesthesia had been performed, and preoperative general condi- tion or performed operation had affected hemodynam- ics greatly. 91 of 5,578 patients were included. All 91 patients received general anesthesia using propofol. We checked type of antidepressants taken and use of vasopressors during anesthesia., Results: Type of antidepressants taken by 91 patients had no effect on the frequency of vasopressor administration. However, 7 of 91 patients showed treatment-resistant refractory hypotension by ephed- rine and phenylephrine. Catecholamines (noradrenaline, dobutamine) were effective. Frequency of refractory hypotension was significantly higher with serotonin and noradrenaline reuptake inhibitors (SNRI) or with two combined antidepressants., Conclusions: Type of antidepressants had no effect on frequency of vasopressor administration. Treat- ment-resistant refractory hypotension by ephedrine and phenylephrine was significantly higher with SNRI or two combined antidepressants. Sympathetic nerve activity may be influenced by interaction of anesthetics and antidepressants in some patients.

Background: It is known that when isobaric bupivacaine is applied for Caesarean delivery, phenylephrine is superior to ephedrine in preventing rostral spread of spinal anesthesia. In this study, we prospectively investigated whether phenylephrine can prevent rostral spread of spinal hyperbaric bupivacaine., Methods: We randomly divided 32 patients undergoing Caesarean delivery into two groups: phenylephrine group and ephedrine group. In both groups, after the spinal injection of 2.0 ml of hyperbaric 0.5% bupivacaine, we started continuous intravenous infusion of phenylephrine or ephedrine. Blood pressure and heart rate were recorded every minute. Block height of cold sensation was assessed at 5, 10 and 15 minutes after the spinal injection. We measured umbilical artery pH after birth. Data were analyzed using a statistical software package., Results: Block height was significantly lower with phenylephrine than with ephedrine at 10 and 15 minutes. Umbilical artery pH was significantly higher with phenylephrine than with ephedrine. Haemodynamic changes were significantly different between the two groups. There were no significant differences in age, BMI and spinal-delivery intervals., Conclusions: 1. Phenylephrine prevented rostral spread of spinal hyperbaric bupivacaine. 2. Haemodynamic changes were significantly different between the two groups. 3. Umbilical artery pH was significantly higher with phenylephrine than with ephedrine.

We studied the effect of oral administration of the extracts from MBST and its component chinese plants, and 1-ephedrine on 48 hr homologous passive cutaneous anaphylaxis (PCA), and histamine- or serotonin-induced skin reaction in rats. Administration (100-1,000 mg/kg) of MBST 1 hr before antigen challenge dose-dependently inhibited PCA. Skin reaction induced by histamine was also inhibited by this formula at 1,000 mg/kg 1 hr prior to the provocation in some degree. The inhibitory component of MBST of PCA was found to be Mao. Further examinations revealed that 1-ephedrine, which is contained in Mao in a large amount, did not substantially inhibit histamine- or serotonin-induced skin reaction. These results indicate that MBST has a significantly inhibitory activity on PCA, to which 1-ephedrine from Mao in the formula almost totally contributes, through the inhibition of chemical mediator release. Since MBST showed some inhibition of histamine-induced skin reaction, on which 1-ephedrine did not affect, it is suggested that some ingredient of MBST responsible for inhibition of PCA may be involved in addition to 1-ephedrine.

We investigated the effects of ephedrine (EP) and phenylephrine (PH) on partial pressure of oxygen and intra-pulmonary shunt during one-lung ventilation under general anesthesia with enflurane, fentanyl and oxygen. When systolic blood pressure decreased to less than 80% of the resting values, 30 adult patients who were randomly assigned into 2 groups, received either EP 0.15 mg.kg-1 or PH 2 micrograms.kg-1. In group-EP, PaO2 increased significantly from 187 +/- 112 to 205 +/- 114 mmHg (FIO2 = 1.0, P < 0.05), while in group-PH, PaO2 changed from 209 +/- 129 to 248 +/- 84 mmHg without statistical significance. Intra-pulmonary shunts were essentially unchanged in both groups. Neither dysrhythmia, ST-T changes on electrocardiography, congestive heart failure, nor severe hypoxemia were observed in any patient during the study. These results indicate that EP and PH in above doses can be safely administered to treat arterial hypotension during one-lung ventilation.

Effects of repeated administration of ephedrine (EPH) 40 and 80 mg/kg sc, and 20, 40, and 80 mg/kg ip on ambulatory activity in adult male mice of the dd strain were investigated. The drug was administered 5 times at intervals of 1 and 7 days. The ambulatory activity of each mouse was measured by a tilting-type round activity cage of 25 cm in diameter for 150-210 min after the drug administration. Repeated administration of EPH 80 mg/kg ip produced a marked augmentation in the sensitivity of the mouse, i.e. reverse tolerance, to the ambulation-increasing effect of the drug regardless of the administration intervals. However, repeated administration of 80 mg/kg sc and 40 mg/kg ip at intervals of 7 days caused a slight reverse tolerance, while 40 mg/kg sc at intervals of 7 days as well as 20 and 40 mg/kg ip at intervals of 1 day did not produce reverse tolerance. In contrast, a poorer development of reverse tolerance to the ambulation-increasing effect of EPH was observed when a mouse was confined in a glass jar of 5 cm in diameter to impede ambulation for 150-180 min after each administration. Mice showing reverse tolerance to EPH demonstrated an increased sensitivity to methamphetamine as compared with the saline-pretreated control mice. The present results suggest that the characteristics of reverse tolerance to ambulation-increasing effect of EPH are almost identical with those after methamphetamine and methylphenidate.

The action of d-psuedoephedrine on bronchial smooth muscle, respiratory resistance and blood pressure was compared with that of 1-ephedrine. The following results were obtained. 1) Administration of dl-isoproterenol on isolated guinea pig tracheal muscle previously constricted with acetylcholine (ACh) or histamine (his) was the most effective and d-pseudoephedrine had the same effect as 1-ephedrine. The relaxing effect of dl-isoproterenol, 1-ephedrine or d-pseudoephedrine on ACh or His induced tracheal constriction was competitively antagonized by the pretreatment of propranolol. 2) The intravenous or sublingual administration of d-pseudoephedrine on the increased respiratory resistance induced by His produced the same effect as 1-ephedrine. 3) The increase in blood pressure with d-pseudoephedrine was weaker than that of 1-ephedrine. 4) When 1-ephedrine of d-pseudoephedrine was repeatedly injected into the same animal, signs of tachyphylaxis were observed. It was found that d-pseudoephedrine, the main alkaloid of Ephedrine Helba, exhibited the relaxing effect on bronchial smooth muscles as did 1-ephedrine. The respiratory resistance increased by His was inhibited by the sublingual administration of d-pseudoephedrine and 1-ephedrine.

Some pharmacological actions of intraperitoneally (i.p.) administered d-pseudoephedrine (d-pseudo) on the central nervous system of mice were compared with those of l-ephedrine (l-eph). Locomotor activity was increased by l-eph (50, 100 and 200 mg/kg,) but not by d-pseudo (50, 100 and 200 mg/kg). Wheel-revolving activity was reduced by a 200 mg/kg dose of both drugs. Rectal temperature was increased by l-eph at 50, 100 and 200 mg/kg. However, it was decreased by 50 and 100 mg/kg doses of d-pseudo, and the change in response to 200 mg/kg of d-pseudo was biphasic, decreasing first and increasing subsequently. Pentobarbital-induced sleeping time was shortened by l-eph (50 and 100 mg/kg), but was not influenced by any of the doses of d-pseudo. In the experiment on locomotor activity, L-3,4-dihydroxyphenylalanine (400 mg/kg, i.p.) potentiated the effects of d-pseudo and l-eph, but reserpine (1 mg/kg, day X 5 days, i.p.) and 6-hydroxydopamine (40 micrograms/mouse, intracerebroventricular injection) potentiated only the effect of l-eph. These results suggest that the effect of d-pseudo on the central nervous system of mouse is not only weaker than that of l-eph, but also the mechanisms of action of these two substances are different.

Effects of repeated oral administration of a commercial preparation of antitussive and expectorant, BRON-W Solution (SS Pharmaceut., BRON; 10ml/kg), and of single and combination of dihydrocodeine (2HCOD; 10mg/kg), methylephedrine (MEPH; 20mg/kg), caffeine (CAF; 20.6mg/kg) and chloropheniramine (CPA; 4mg/kg) were investigated by means of ambulatory activity in mice. The drug doses tested were identical with those in BRON 10ml/kg. The drug administration was conducted 5 times at intervals of 3-4 days. Furthermore, 4 days after the final treatments, all mice were given methamphetamine 2 mg/kg s.c. In the single administration regimen of individual drugs, only CAF significantly increased the ambulatory activity. However, there was no significant change in the ambulation-increasing effect of CAF after the repeated administration. The other 3 drugs failed to elicit any marked change in the activity throughout the 5 times administration. Such the repeated administration of the individual drugs induced no significant change in the sensitivity to the ambulation-increasing effect of methamphetamine. BRON and BRON-corresponding combination of 4 drugs increased the ambulatory activity in the 1st administration, and the ambulation-increasing effect was progressively enhanced by the repeated administration of these preparations. On the other hand, although CAF-containing solutions significantly increased the ambulatory activity in the 1st administration, the proportions of the changes in the ambulatory activity during the repeated administration regimen were different from that observed after BRON. The combined administration of 2HCOD + MEPH + CPA failed to increase the ambulatory activity in the 1st administration, but significantly increased it in the 2nd and 3rd administration, then elicited again no significant increase in the activity in the 4th and 5th administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of oral administration of a commercial preparation of an antitussive and expectorant (BRON-W Solution, SS Pharmaceut., BRON), and of its constituents; dihydrocodeine (2HCOD), methylephedrine (MEPH), caffeine (CAF) and chloropheniramine (CPA), were behaviorally investigated by means of ambulatory activity and discrete lever-press avoidance response in mice. In 1ml of BRON, 2HCOD 1mg, MEPH 2mg, CAF 2.06mg and CPA 0.4mg are contained with 0.25ml of Senega sirup. BRON 5 and 10ml/kg increased the ambulatory activity in a dose-dependent manner, and suppressed the avoidance response at 10ml/kg. Similar behavioral effects were reproduced by the administration of a mixed solution, in which 2HCOD, MEPH, CAF and CPA were contained at the same doses with those in BRON 10ml/kg. However, such the effects could not be observed after the administration of the drug solutions in which CAF was not contained. The combined administration of 4 drugs at the doses corresponding to 40ml/kg of BRON elicited significant increase in the ambulatory activity and disruption of the avoidance response, eliciting a decrease in the avoidance rate. Though these behavioral effects markedly changed when CAF was eliminated from the solution, an elimination of either 2HCOD, MEPH or CPA was also effective to modify the behavioral effect. Furthermore, combined administration of 4 drugs and MEPH + CAF + CPA at the doses equivalent to those contained in 40ml/kg of BRON produced death of 1 or 2 mice out of 10-14. The present results suggest that the ambulation-increasing and avoidance-suppressing effects of BRON were mainly produced by CAF, and that 2HCOD, MEPH and CPA are also involved therein. In addition, there is a possibility of acute death during BRON-abuse.

Injection of a low dose of clonidine showed the biphasic blood pressure response which comprises a delayed onset of long lasting hypotension and a quick onset of hypertension of short duration followed by the former, in the alpha-chloralose-urethanized rat. A second injection of low dose of clonidine administered 90 min after the first showed only two peaks of pressor response, no longer a depressor one, and tachyphylaxis occurred with repeated injections of the same dose of clonidine, together with a gradual elevation of blood pressure level. Furthermore, the depressor action was inhibited by pretreatment with cocaine or imipramine. In contrast, injection of a high dose of clonidine exhibited pressor response with only two peaks, duration of which was markedly potentiated by pretreatment with cocaine or imipramine, and also by guanethidine, but inhibited in reserpinized and spinal rats. While the blood pressure was sustained at a high level after the injection of a high dose os clonidine, blood pressure reversal was produced by tyramine, due to possible beta-mimetic action of much greater amounts of catecholamines released by tyramine. The isolated guinea-pig vas deferens contracted when treated with clonidine, and this contraction was inhibited in the reserpinized preparation. This inhibition was recovered by incubation with norepinephrine. Interaction between tyramine and clonidine was also seen in vitro, but it disappeared in the reserpinized, denervated or propranolol-pretreated guinea-pig vas deferens. The contraction of the vas deferens induced by clonidine was potentiated by pretreatment with cocaine, but not by pretreatment with guanethidine, ans was inhibited by treatment with alpha-adrenergic blocking agents phentolamine and phentolame and phenoxybenzamine, but not by tolazoline.