Phenoxybenzamine Research Articles

Identification and Characterization of New Impurity in Phenoxybenzamine Hydrochloride Drug Substance

Identification and Characterization of New Impurity in Phenoxybenzamine Hydrochloride Drug Substance

Influence of duration of preoperative treatment with phenoxybenzamine and secretory phenotypes on perioperative hemodynamics and postoperative outcomes in pheochromocytoma and paraganglioma.

Resection of pheochromocytoma and paraganglioma (PPGL) carries risks with perioperative hemodynamic instability. Phenoxybenzamine (PXB) is a commonly used α-blockade to prevent it. It is unclear whether lengthening the preoperative duration of PXB is better for hemodynamic stability and postoperative outcomes. Furthermore, different types of catecholamines have varying effects on perioperative hemodynamics. Thus, our study aimed to investigate the impact of the duration of preoperative preparation with PXB and secretory phenotypes of the patients on intraoperative hemodynamic stability and postoperative complications in PPGL. Between Dec 2014 and Jan 2022, 166 patients with PPGL were operated on by the same team at Sun Yat-sen Memorial Hospital. They were divided into group A(1-14d), Group B(15-21d), and Group C(>21d) based on the duration of management with PXB and into the adrenergic and the noradrenergic phenotype group based on secretory profiles. Data on intraoperative hemodynamics and postoperative outcomes were collected and compared among groups. A total of 96 patients occurred intraoperative hemodynamic instability, and 24 patients had 29 postoperative complications related to the surgery. Among the 145 patients treated with PXB, no significant differences were found in the cumulative time outside the target blood pressure(6.67%[0-17.16%] vs. 5.97%[0-23.08%] vs. 1.22%[0-17.27%], p=0.736) or in the median total HI-score(42.00[30.00-91.00] vs. 89.00[30.00-113.00] vs. 49.00[30.00-93.00], p=0.150) among group A(n=45), B(n=51) and C(n=49). Multivariate analysis demonstrated that the level of plasma-free metanephrine(MN) was an independent risk factor for intraoperative hemodynamic instability. And the median cumulative time outside of the target blood pressure in the adrenergic phenotype group was significantly greater than that in the noradrenergic phenotype group(8.17%[0-26.22%] vs. 1.86%[0-11.74%], p=0.029). However, the median total HI-score(99.50[85.00-113.25] vs. 90.00[78.00-105.00], p=0.570) and postoperative outcomes showed no differences between the two groups. A preoperative duration of nearly 14 days with PXB is sufficient for ensuring intraoperative hemodynamic stability in PPGL. And lengthening the preparation duration may not provide additional benefits in the era of widespread application and advanced techniques of laparoscopic surgery. Additionally, patients with the adrenergic phenotype are more prone to intraoperative hemodynamic instability than the noradrenergic phenotype. Thus, more attention should be given to the adrenergic phenotype during surgery.

Sustained vascular contractile response induced by an R- and S-epimer of the ergot alkaloid ergocristine and attenuation by a noncompetitive antagonist.

Vasoconstriction is a known effect associated with ergot alkaloid consumption. The vascular contractile responses are often sustained for an extended period after exposure. Ergot alkaloids exist in two molecular configurations, the C-8-(R)-isomer (R-epimer) and the C-8-(S)-isomer (S-epimer). The sustained vascular contractile response to the R-epimers has been studied previously, unlike the S-epimers which are thought to be biologically inactive. Additionally, antagonists have been utilized to attenuate the vascular contraction associated with the R-epimers of ergot alkaloids utilizing ex vivo techniques. This study utilized an arterial tissue bath to examine and compare the sustained vascular contractile response attributed to ergocristine (R) and ergocristinine (S) using dissected bovine metatarsal arteries. The contractile blocking effect of a noncompetitive alpha-adrenergic antagonist, phenoxybenzamine (POB), was also investigated in precontracted arteries. Arteries (n = 6/epimer) were exposed to a single dose of ergocristine or ergocristinine (1 × 10−6 M in buffer). Each of the epimer doses was followed by a POB (1 × 10−3 M) or methanol (control) treatment at 90 min and the response was observed for another 90 min. Both epimers produced a sustained contractile response over the 180-min incubation period in the control groups. The R-epimer caused a greater sustained contractile response from 60 to 180 min post epimer exposure, compared to the S-epimer (P < 0.05, generalized estimating equations, independent t-test). Phenoxybenzamine caused a decrease in the contractile response induced by ergocristine and ergocristinine from 105 to 180 min, compared to the control (P < 0.05, generalized estimating equations, paired t-test). Overall, these results demonstrate the presence of a sustained vascular contractile response attributed to the R- and S-epimer of an ergot alkaloid with differences in contractile response between the epimers, suggesting differences in receptor binding mechanisms. Furthermore, this study demonstrated that a noncompetitive antagonist could attenuate the sustained arterial contractile effects of both ergot configurations ex vivo. Additional investigation into S-epimers of ergot alkaloids is needed. This research contributes to the understanding of the ergot epimer-vascular receptor binding mechanisms, which may support the investigation of different approaches of minimizing ergot toxicity in livestock.

Regulatory effects of cervical sympathetic trunk and renal sympathetic nerve activities on cerebral blood flow during head-down postural rotations.

This study attempts to clarify the neural control of cerebral blood flow (CBF) during head-down postural rotation, which induces a cephalad fluid shift in urethane-anesthetized rats. The animals were placed on a table, tilted to a 45° head-down position over 5s and maintained in that position. Head-down rotation (HDR) induced a transient decrease (8±3mmHg; mean±SE) in mean arterial blood pressure (ABP) at 7.3±0.3s after the onset of HDR. The pressure returned to the pre-HDR level within 1min in the head-down position. Pretreatment with hexamethonium bromide suppressed the HDR-elicited decrease in ABP, suggesting that the decrease in ABP was induced by the suppression of autonomic neural outflow. The administration of phenoxybenzamine (PB), an α-adrenergic antagonist, also eliminated the HDR-elicited decrease in ABP, suggesting that this decrease was elicited by the suppression of α-adrenergic vascular tone. To test sympathetic outflow during HDR, renal sympathetic nerve activity (RSNA) and cervical sympathetic trunk (CST) activity (CSTA) were recorded. RSNA was transiently suppressed at 2.3±0.4s after HDR onset, followed by a decrease in ABP, suggesting that this decrease was, at least in part, induced by the suppression of sympathetic nerves. CSTA did not change significantly during HDR. These results suggest that HDR suppresses sympathetic nerves in the lower body rather than in the head, which might result in a decrease in ABP. To test the effect of the decrease in ABP due to sympathetic activity on CBF during HDR, changes in CBF during HDR were measured. CBF did not change significantly during HDR in the control group after the administration of an α-receptor blocker or after denervation of the CSTs. These results suggest that the impact of the CSTs on CBF is likely to be limited by a rapid increase in CBF due to HDR-elicited cephalad fluid shift and that CBF autoregulation proceeds through an alternative mechanism involving the myogenic properties of cerebral vessels.

Clarification of the USP compendial procedure for phenoxybenzamine hydrochloride via updating impurity profiles

The current United States Pharmacopeia–National Formulary (USP–NF) and the British Pharmacopoeia phenoxybenzamine (PBA) hydrochloride drug substance and drug product monographs describe an HPLC procedure for the determination of a specified impurity “tertiary amine phenoxybenzamine” and use the resolution of an “unknown related substance” from PBA as a system suitability criterion; however, neither structural information of the “unknown related substance” is provided nor reference standards of the two impurities are available. The ambiguity in pharmacopeias poses difficulties in implementing the procedure for quality control. To clarify the degradation pathways, and incorporate the impurity profile of PBA into the USP monographs, the degradation of PBA was revisited. PBA undergoes rapid degradation in neutral or basic aqueous solutions to generate the “tertiary amine phenoxybenzamine” as the predominant degradation product, which was confirmed as phenoxybenzamine hydroxide (PBA-OH). In addition, the “unknown related substance” was proposed as the phenoxybenzamine nitrile (PBA-CN) on the basis of LC–MS studies. The identity of PBA-CN was unambiguously verified via chemical synthesis, HPLC and NMR analyses. A stability-indicating method was developed and validated for the determination of PBA and its impurities, and was used to support USP monograph modernization.

Preparation of a thiols β-cyclodextrin/gold nanoparticles-coated open tubular column for capillary electrochromatography enantioseparations.

Inspired by the distinct chemical and physical properties of nanoparticles, here a novel open-tubular capillary electrochromatography column was prepared by electrostatic assembly of poly(diallydimethylammonium chloride) onto the inner surface of a fused-silica capillary, followed by self-adsorption of negatively charged SH-β-cyclodextrin/gold nanoparticles. The formation of the SH-β-cyclodextrin/gold nanoparticles coated capillary was confirmed and characterized by scanning electron microscopy and energy dispersive spectrometry. The results of scanning electron microscopy and energy dispersive spectrometry studies indicated that SH-β-cyclodextrin/gold nanoparticles were successfully coated on the inner wall of the capillary column. The performance of the SH-β-cyclodextrin/gold nanoparticles coated capillary was validated by the analysis of six pairs of chiral drugs, namely zopiclone, carvedilol, salbutamol, terbutaline sulfate, phenoxybenzamine hydrochloride, and ibuprofen. Satisfactory enantioseparation results were achieved, confirming the use of gold nanoparticles as the support could enhance the phase ratio of the open-tubular capillary column. Additionally, the stability and reproducibility of the SH-β-cyclodextrin/gold nanoparticles coated capillary column were also investigated. Then, this proposed method was well validated with good linearity (≥0.999), recovery (90.0-93.5%) and repeatability, and was successfully used for enantioseparation of ibuprofen in spiked plasma samples, which indicated the new column's potential usage in biological analysis.

The Duration of Preoperative Administration of Single α-Receptor Blocker Phenoxybenzamine before Adrenalectomy for Pheochromocytoma: 18 Years of Clinical Experience from Nationwide High-Volume Center.

Purpose There is no consensus for the optimum duration of preoperative administration of phenoxybenzamine (PXB) before adrenalectomy for pheochromocytoma. The aim of this study is to investigate whether perioperative hemodynamics and postoperative outcomes are related to the duration of PXB administration. Methods In total, 102 patients managed preoperatively with single α-receptor blocker phenoxybenzamine were enrolled from 469 consecutive patients diagnosed histologically with pheochromocytoma. The patients received surgical treatment in the Department of Urology, Peking University First Hospital, between January 2001 and July 2018. All patients were divided into three groups: Group A (<14 d), Group B (14–30 d), and Group C (>30 d). Patient and tumor characteristics, intraoperative hemodynamics, and postoperative outcomes were recorded and compared among the three groups. Results These patients included 47 men and 55 women, with an average age of 43 years at the time of surgery. Clinical characteristics, except the status of preoperative biochemical tests (24 hr urine fractioned catecholamine or plasma-fractioned catecholamine) (p=0.020), preoperative hemodynamics, and medicine management and surgical approaches, in the three groups were comparable. Multivariate analyses demonstrated that the size of the tumor (p=0.034) was an independent risk factor for intraoperative hemodynamic instability. Among the three groups, we found no significant difference in intraoperative hemodynamics and postoperative outcomes. Conclusion The data from the current study indicated that the preoperative management of pheochromocytoma with single α-receptor blocker PXB for more than 2 weeks, after the final dose adjustment, could not further reduce the risk of intraoperative hemodynamic instability or postoperative complications. Thus, our study supports that 14 days would be enough for the duration of preoperative management of pheochromocytoma with single α-receptor blocker PXB in final dose.

Analysis of clinical characteristics for hypertensive attack during pheochromocytoma and paraganglioma operation: a single center case report of 219 cases

Objective To analyze the clinical characteristics for hypertensive attack during operation and clinical experience of preoperative evaluation and preparation in patients with pheochromocytoma and paraganglioma(PHEO/PGL). Methods A total 219 PHEO/PGL cases from September 2016 to September 2018 were retrospectively reviewed. It included 99 males and 120 females, aged 13 to 76(average 47)years old.The mean diameter of tumor was 5.3 cm(1.5-18.0 cm).140 cases were unilateral PHEO, 6 cases were bilateral PHEO, 68 cases were PGL(jugular, mediaphragm, heart, retroperitoneum, pelvic and bladder) and 5 cases were PHEO combined with PGL. Preoperative highest systolic blood pressure (SBP)was 240 mmHg(1 mmHg=0.133 kPa) and highest diastolic blood pressure(DBP) was 160 mmHg. 20 cases were occult PHEO without hypertension. 217 cases accepted preoperative preparation of alpha-blocker [phenoxy-benzamine, dosage ranging from 5 mg Q12h to 40 mg Q8h, maximum dosage not exceeding 1 mg/(kg·24 h)]. 2 cases did not accept preoperative preparation. All cases accepted open or endoscope surgery. The patients were divided into 2 groups depending on the presence or absence of hypertensive attack at the time of surgery. Patient demographic characteristics and preoperative evaluations were assessed for their prognostic relevance with respect to hypertensive attack. Results Histopathological results showed that all cases were PHEO or PGL, while 205 cases were benign, 14 cases were malignant. Hypertensive attack were recorded in 112 cases(51%). The diameter of tumors in the hypertensive attack group were larger than that in the non-hypertensive attack group[(6.70±2.95)cm vs.(3.95±1.70)cm, P=0.005]. There was no significant difference between the two groups among age[(51.0±10.8)years vs.(38.5±17.6)years, P=0.105], preoperative catecholamine level [norepinephrine (111.20±41.49)μg/24 h vs.(419.15±154.81)μg/24 h, P=0.075], time of use of alpha blockers[(53.0±7.5)d vs.(38.0±6.4)d, P=0.139], daily dosage of alpha blocker[(40.0±7.2)mg vs.(27.1±1.8)mg, P=0.111] and blood pressure at diagnosis[(173.75±26.69)mmHg vs.(155.0±20.75)mmHg, P=0.139]. Among 219 cases, 2 case had emergency hemostasis after operation, 1 case had catecholamine cardiomyopathy after operation for occult pheochromocytoma, and no perioperative death occurred. Conclusions Patients with large tumor tend to have hypertensive attack during operation so that should be better prepared. Key words: Pheochromocytoma; Paraganglioma; Alpha-blockade; Hypertension

The characteristics of peroperative blood pressure and heart rate in patients with normotensive incidental pheochromocytomas

Objective To investigate the characteristics of peroperative blood pressure and heart rate in patients with normotensive incidental pheochromocytomas in order to provide the basis for peroperative treatment. Methods This retrospective study collected the data of 104 patients with a pathological diagnosis of unilateral pheochromocytoma at PLA General Hospital during January 2011 to December 2016. They were divided into normotensive incidental pheochromocytomas(NIP)group(n=50)if the patients were normotensive and HIP group(n=54)if the patients were with hypertension. The clinical features, imaging features and peroperative hemodynamics were analyzed. Results (1)The age, urinary norepinephrine, daily dosage and duration of phenoxybenzamine in NIP group were less than those of HIP group(all P<0.05). (2)Preinduction blood pressure, maximum blood pressure, and total fluid intake in NIP group were lower than those in HIP group(all P<0.05). The blood pressure range, heart rate range, increased blood pressure, minimum mean arterial pressure, vasoactive medication were without statistical significance between these two groups.(3)The times and rate of intraoperative systolic blood pressure more than 30% baseline, 200 mmHg(1 mmHg=0.133 kPa), 180 mmHg, 160 mmHg, intraoperative tachycardia, bradycardia, intraoperative hypotension and postoperative hypotension were without statistical significance between these two groups.(4)Stratified analysis of age(50 years), phenoxybenzamine(40 mg/d), tumor diameter(50 mm)and preinduction blood pressure(130/80 mmHg)showed that intraoperative blood pressure and heart rate were without statistical significance between these two groups.(5)There was no correlation between phenoxybenzamine(daily dosage or duration)and peroperative hypotension. Applying phenoxybenzamine or vasoactive medication was not correlated with peroperative hypotension in NIP group. Conclusion The peroperative blood pressure and heart rate of patients with NIP are similar to those of patients with HIP. Adequate peroperative treatment should be applied to NIP to avoid hemodynamic instability. (Chin J Endocrinol Metab, 2018, 34: 466-471) Key words: Pheochromocytoma; Hypertension; Peroperation; Blood pressure; Heart rate

Identification of serotonin 2A receptor as a novel HCV entry factor by a chemical biology strategy

ABSTRACTHepatitis C virus (HCV) is a leading cause of liver disease worldwide. Although several HCV protease/polymerase inhibitors were recently approved by U.S. FDA, the combination of antivirals targeting multiple processes of HCV lifecycle would optimize anti-HCV therapy and against potential drug-resistance. Viral entry is an essential target step for antiviral development, but FDA-approved HCV entry inhibitor remains exclusive. Here we identify serotonin 2A receptor (5-HT2AR) is a HCV entry factor amendable to therapeutic intervention by a chemical biology strategy. The silencing of 5-HT2AR and clinically available 5-HT2AR antagonist suppress cell culture-derived HCV (HCVcc) in different liver cells and primary human hepatocytes at late endocytosis process. The mechanism is related to regulate the correct plasma membrane localization of claudin 1 (CLDN1). Moreover, phenoxybenzamine (PBZ), an FDA-approved 5-HT2AR antagonist, inhibits all major HCV genotypes in vitro and displays synergy in combination with clinical used anti-HCV drugs. The impact of PBZ on HCV genotype 2a is documented in immune-competent humanized transgenic mice. Our results not only expand the understanding of HCV entry, but also present a promising target for the invention of HCV entry inhibitor.

Adrenal cholangiocarcinoma: a case report and literature review

Objective To discuss the clinical characteristics and pathologic features of adrenal cholangiocarcinoma. Methods We reported one extremely rare adrenal cholangiocarcinoma case and review the relative literature. A 71-year-old male was admitted with right adrenal mass for 2 months. Patient has been suffered from hypertension and controlled by oral drugs for ten years. Enhanced computerized tomography (CT) revealed a mass in right adrenal gland area, with the size of 7.1 cm×6.8 cm×4.4 cm and inhomogeneous enhancement in arterial phase. Adrenal functional examination showed no obvious abnormalities of serum catecholamine, supine RAAS, cortisol determination and rhythm and urine VMA detection. Results After medical preparation of phenoxybenzamine for 3 weeks preoperatively, the patient's blood pressure was maintained at 110-125/80-90 mmHg and with stuffy nose and ruddy nail bed. The patient′s weight gained of 1kg than before. Retroperitoneal laparoscopic resection of right adrenal tumor was performed in general anesthesia. The tumor that related to the inferior vena cava and liver was successfully removed without any other damage. The operation time was 155 min and estimated blood volume was 50 ml. Perioperative blood pressure of patient was stable and recovery was well. According to clinical characteristic and pathological test and immunohistochemical results, patient was diagnosed with adrenal cholangiocarcinoma. Followed up for 15 months, no tumor recurrence and metastasis based on ultrasound examination and CT, and with normal blood pressure. Conclusions Adrenal cholangiocarcinoma was extremely rare type in the adrenal malignant tumors based on hepato-adrenal fusion histologically. This case constitutes a contribution for the knowledge of adrenal cholangiocarcinoma. The imaging findings were heterogeneous enhancement of soft tissue masses, and there was no obvious abnormality in adrenal functional examination. The retroperitoneal laparoscopic surgery is a treatment choice for this kind of patient. Key words: Adrenal gland neoplasm; Cholangiocarcinoma; Adrenalectomy

Perioperative hemodynamics and outcomes of patients on metyrosine undergoing resection of pheochromocytoma or paraganglioma

IntroductionTo describe outcomes of patients with metyrosine (MET) pretreatment for abdominal surgical resection of pheochromocytoma or paraganglioma (PCC/PGL) compared with patients who had phenoxybenzamine (PBZ) pretreatment. MethodsRetrospective review of perioperative outcomes for PCC/PGL patients treated with MET and propensity-matched comparison of MET and PBZ (MET + PBZ) with PBZ alone. ResultsMET preparation was given in 63 cases (26 laparoscopic and 37 open, of which 55 also received PBZ). All patients had wide perioperative hemodynamic oscillations. Patients with open procedures required more intravenous fluids and blood transfusions; 35% required postoperative vasopressor infusions for hypotension and 38% developed acute kidney injury. One laparoscopic procedure required postoperative vasopressor infusion, and 12% of patients developed acute kidney injury. Forty-five MET + PBZ patients were propensity-matched with PBZ-only patients. Intraoperatively, MET + PBZ patients had lower minimum systolic and diastolic blood pressures than PBZ-only patients (median systolic, 74 vs 80 mm Hg, P = 0.01; median diastolic, 42 vs 46 mm Hg, P = 0.005) and larger intraoperative blood pressure oscillations (median systolic range, 112 vs 93 mm Hg, P = 0.06; median diastolic range, 58 vs 51 mm Hg, P = 0.02). Postoperative vasopressor infusion use was similar between MET + PBZ and PBZ only (16% vs 11%, P = 0.76). Major outcomes were not different between regimens. ConclusionLarge hemodynamic oscillations were present in our PCC/PGL patients treated with MET + PBZ. These patients had a wider range of intraoperative blood pressure variations than PBZ-only patients. No differences in postoperative comorbid outcomes were found between MET + PBZ and PBZ-only groups.

Alpha blockers: A relook at phenoxybenzamine

Phenoxybenzamine (PBZ) is an alpha adrenergic antagonist, used for the management of hypertension. PBZ acts by blocking alpha-adrenergic receptors, leading to vasodilatation and low systemic vascular resistance. This helps in control of blood pressure in pheochromocytoma, improvement of systemic oxygen delivery, and optimization of the Qp/Qs in pediatric cardiac surgery such as hypoplastic left heart syndrome and improving perfusion parameters during open heart surgery. The uses have further extended to causalgia, Raynaud's phenomenon, autonomic hyperreflexia, and even for patency of radial artery conduit in coronary artery bypass grafting surgery. However, its prolonged hypotensive effect limits the regular use. In this review, we discussed the mechanism of action, pharmaco-physiology of PBZ, perioperative uses in different clinical setting and controversies for its uses; publications in different scientific journals from the previous years.

Anti-tumor activity of phenoxybenzamine hydrochloride on malignant glioma cells.

Phenoxybenzamine hydrochloride (PHEN) is a selective antagonist of both α-adrenoceptor and calmodulin that exhibits anticancer properties. The aim of this study was to explore the anti-tumor function of PHEN in glioma. Cell proliferation assay was used to assess glioma cell growth. Migration and invasion capacity of glioma cells was monitored by wound-healing and transwell assay, respectively. Neurosphere formation test was adopted for the tumorigenesis of glioma cells, which was also confirmed by soft agar cloning formation test in vitro and a nude mouse model in vivo. Finally, we explored the potential pathway utilized by PHEN using Western blot and immunofluoresce staining. PHEN exhibited a significant inhibitory effect on the proliferation of both U251 and U87MG glioma cell lines in a positive dose-dependent manner. PHEN apparently attenuated the malignancy of glioma in terms of migration and invasion and also suppressed the tumorigenic capacity both in vitro and in vivo. Mechanism study showed that PHEN promoted tumor suppression by inhibiting the TrkB-Akt pathway. The results of the present study demonstrated that PHEN suppressed the proliferation, migration, invasion, and tumorigenesis of glioma cells, induced LINGO-1 expression, and inhibited the TrkB-Akt pathway, which may prove to be the mechanisms underlying the anti-tumor effect of PHEN on glioma cells.

Chiral aziridine ring opening: facile synthesis of (R)-mexiletine and (R)-phenoxybenzamine hydrochloride

A simple and efficient synthesis of chiral drugs (R)-mexiletine 1, an anti-arrhythmic drug and (R)-phenoxybenzamine hydrochloride 2, an anti-hypertensive drug has been described via controlled reductive ring opening of chiral aziridine as a key step. The target compounds 1 and 2 were obtained in overall yields of 34% and 10.5%, respectively.

Cavernous hemangioma of adrenal： a case report and review of the literature

Objective To study the diagnosis and surgical treatment of adrenal cavernous hemangi -oma. Methods The data of one case with adrenal cavernous hemangioma was retrospectively reviewed .A 62-year-old female patient admitted in out hospital on 18th June, 2013 due to the paroxysmal hypertension for 10 years and finding the left adrenal mass for 2 months.Her highest blood pressure was 175/55 mmHg and the response for the drug treatment was poor .In recent 6 months, her blood pressure was unstable .Ab-dominal ultrasound showed a hypoechoic mass in left adrenal .Enhanced CT examination showed an irregular mass in the left adrenal gland , with the size of 4.5 cm ×2.5 cm ×3.9 cm,peripherally enhanced in arterial phase , contrast agent filling in portal venous phase , and high density in delay phase .Abdominal MR exami-nation showed a mass before abdominal aortic , with clear and smooth edge .The mass showed low signal in T1WI phase and high signal in T 2WI phase, which was considered as pheochromocytoma .24h urinary cate-cholamines showed that norepinephrine was 103.0 nmol, epinephrine was 9.8 nmol and dopamine was 18.9 nmol.Octreotide （99Tcm-TOC） showed slight high expression of somatostatin receptor .Preoperative diagnosis was left pheochromocytoma . Results After the preoperative medical preparation of phenoxybenzamine for 3 weeks, her blood pressure was maintained at 120-132/50-70 mmHg, with stuffy nose, warm hand and foot, and the weight gain of about 1 kg.The patient was undergone laparoscopic resection of left adrenal tumor under general anesthesia on June 24, 2013.The postoperative blood pressure returned to normal .And the left adrenal pathology was cavernous hemangioma .Following up for 5 months, the patient had normal blood pressure without the tumor recurrence . Conclusions The adrenal cavernous hemangioma is extreme-ly rare with high rate of misdiagnosis .For adrenal tumor with typical hemangioma imaging , the diagnosis of cavernous hemangioma should be considered .For tumors larger than 6 cm, surgery is recommended .The first choice of operative approach is laparoscopic resection of adrenal tumor , and normal adrenal tissue should be retained as far as possible. Key words: Cavernous hemangioma of adrenal; Laparoscopic resection of adrenal tumor; Misdiagnosis

Predictors of hemodynamic instability during surgery for pheochromocytoma.

Resection of pheochromocytoma is often associated with hemodynamic instability (HDI). We examined patient and tumor factors that may influence HDI. The effect of pretreatment with nonselective α blockade phenoxybenzamine (PXB) versus selective α blockade on HDI and outcomes was also evaluated. The records of 91 patients who underwent adrenalectomy between 2002 and 2013 were retrospectively reviewed. HDI was determined by number of intraoperative episodes of systolic blood pressure (SBP)>200mmHg, those greater than or less than 30% of baseline, heart rate>110bpm, and the need for postoperative vasopressors. Fishers exact, t test and regressions were performed. Among 91 patients, 78% received PXB, 18% selective α blockade and 4% no adrenergic blockade. Patient demographics, tumor factors and surgical approach were similar among the blockade groups. On multivariate analysis, increasing tumor size was associated with a significant rise in the number of episodes of SBP>30% [rate ratio (RR) 1.40] and an increased postoperative vasopressor requirement [odds ratio (OR) 1.23]. Open adrenalectomy and use of selective blockade were associated with an increased number of episodes of SBP>200mmHg (RR 27.8 and RR 20.9, respectively). Open adrenalectomy was also associated with increased readmissions (OR 12.3), complications (OR 5.6), use of postoperative vasopressors (OR 4.4) and hospital stay (4.6days longer). There were no differences in other HDI measurements or postoperative outcomes among the blockade groups. Tumor size, open adrenalectomy, and type of α blockade were associated with intraoperative HDI during pheochromocytoma resection. Selective blockade was associated with significantly more episodes of intraoperative hypertension but no perioperative adverse outcomes.

Phenoxybenzamine Is Neuroprotective in a Rat Model of Severe Traumatic Brain Injury

Phenoxybenzamine (PBZ) is an FDA approved α-1 adrenergic receptor antagonist that is currently used to treat symptoms of pheochromocytoma. However, it has not been studied as a neuroprotective agent for traumatic brain injury (TBI). While screening neuroprotective candidates, we found that phenoxybenzamine reduced neuronal death in rat hippocampal slice cultures following exposure to oxygen glucose deprivation (OGD). Using this system, we found that phenoxybenzamine reduced neuronal death over a broad dose range (0.1 μM–1 mM) and provided efficacy when delivered up to 16 h post-OGD. We further tested phenoxybenzamine in the rat lateral fluid percussion model of TBI. When administered 8 h after TBI, phenoxybenzamine improved neurological severity scoring and foot fault assessments. At 25 days post injury, phenoxybenzamine treated TBI animals also showed a significant improvement in both learning and memory compared to saline treated controls. We further examined gene expression changes within the cortex following TBI. At 32 h post-TBI phenoxybenzamine treated animals had significantly lower expression of pro-inflammatory signaling proteins CCL2, IL1β, and MyD88, suggesting that phenoxybenzamine may exert a neuroprotective effect by reducing neuroinflammation after TBI. These data suggest that phenonxybenzamine may have application in the treatment of TBI.

Prospective Study to Compare Peri‐operative Hemodynamic Alterations following Preparation for Pheochromocytoma Surgery by Phenoxybenzamine or Prazosin

Prospective studies comparing the efficacy of selective versus nonselective alpha blockers for preoperative preparation of pheochromocytoma (PCC) are lacking. In this prospective nonrandomized study, we compared the outcome of preoperative preparation with phenoxybenzamine (PBZ) and prazosin (PRZ) in terms of perioperative hemodynamic alterations. The study was conducted at a tertiary referral center from July 2010 to December 2012. Thirty-two patients with PCC underwent operation after adequate preparation with PBZ (n = 15) or PRZ (n = 17). Five pediatric and adolescent patients were excluded because of different hemodynamics in this population. Perioperative monitoring was done for pulse rate (PR) and blood pressure(BP) alterations, occurrence of arrhythmias, and time taken to achieve hemodynamic stability. Groups were compared with the Mann-Whitney test, Student's t test, and the χ2 test as applicable. Patients in the two groups were similar in age,gender, 24 h urinary metanephrine and normetanephrine levels, and type of procedure. Patients prepared with PRZ had significantly more intraoperative episodes of transient hypertension (systolic BP ≥ 160 mmHg) and hypertensive urgency (BP >180/110 mmHg) (p 0.02, 0.03, respectively). More patients receiving PRZ suffered from transient severe hypertension (SBP ≥ 220 mmHg) (p 0.03). The PRZ group also had more median maximum SBP (233 mmHg vs PBZ 181.5 mmHg) (p = 0.01) and lesser median minimum SBP (71 mmHg vs PBZ 78 mmHg) (p 0.03). No significant differences were found between the study groups for changes in PR, postoperative BP alterations,occurrence of arrhythmias, and time taken to achieve hemodynamic stability. PBZ was found superior to PRZ in having fewer intraoperative hemodynamic fluctuations.

An unusual case of paraganglioma

Pheochromocytomas or Paragangliomas are neroendocrine tumors elaborating catecholamines. They may not present always in a classic manner and a high degree of suspicion is important in diagnosing them early. They can grow large enough to impinge on the great vessels and yet symptoms may not indicate the severity until late. A young African 32 year old Male presented with occasional headaches, moderate weight loss, abdominal pain and hypertension for three years. On investigation for hypertension a large paraganglioma was discovered wrapped around the Aorta and vena cava. He was operated successfully after preoperative preparation and was discharged normotensive.Conclusion:Young hypertensive should always be worked up fully including checking for abdominal masses. The classic paroxysm was absent in this case. After surgical removal the catecholamines elaborated by the tumor also take time to be washed out of the circulation thus the blood pressure will need careful monitoring. Conventional alpha blockage first and beta blockage later was the algorithm followed but choice of agent was also discussed with nesthethesiologist. Though classically taught phenoxy benzamine is used, in this case it was not used and a combination of Prazosin and Propranolol