1、DOXAZOSIN用在 PHEOCHROMOCYTOMA (嗜鉻細胞瘤,如:腎上腺髓質瘤 )的治療評估,99.05.28 主講人:謝曉瑩 藥師 指導藥師:張秀玲 藥師,Question,Question,Patient History,63歲，男性 Past historysuspect adhesion ileusDiadetes Mellitus , type 2HypertentionChronic Kidney DiseaseSuspected malignant pheochromocytoma with multiple para-aortic lymph nodes and li
2、ver metastasis.Complicated with fluctuated blood pressure, peripheral vessel and bowel ischemia episodes,Lab Data,Creatinine (1.1-1.5mg/dL),Norepinephrine (11.1-85.5mcg/day),1213.95,2028.27,1835.6,2,9.8,4.1,5.7,Drug Profile,1# BID,1# QD,1# BID,2# BID,1#QID,1# QD,BP=132/95 , HR=108 Increase Doxazosin
3、 dose to 2# bid for pheochromocytoma management. Increase Indera 1# to qid for palpitation and blood pressure treatment.,1# BID,Pheochromocytoma,Diagonsis Treatment Conclusion,Pheochromocytoma,Phaeochromocytomas(PHEOs) are catecholamine-producin neuroendocrine tumours arising from chromaffin cells o
4、f the adrenal medulla or extra-adrenal paraganglia.Pheochromocytoma is characterized by hypertension which is typically paroximal, but may be persistent. About 0.6% of all hypertensive patients were due to pheochromocytoma. 1,The diagnosis of pheochromocytomas depends mainly upon the demonstration o
5、f catecholamine excess by 24-h urinary catecholamines and metanephrines or plasma metanephrines.,Pheochromocytoma,-blocker,-blocker,Vasodilator,CCBs,PHENOXYBENZAMINE HYDROCHLORIDE Adults (initial): 10 mg orally twice daily; titrate to maintenance; may increase dose every other day to 20 to 40 mg ora
6、lly 2 to 3 times daily Pediatrics: 1 to 2 mg/kg/day orally in divided doses PHENTOLAMINE MESYLATE Adults: 1 to 5 mg boluses IV (maximum dose 15 mg) Pediatrics: 0.05 to 0.1 mg/kg/dose IV DOXAZOSIN,LABETALOL HYDROCHLORIDE Adults: 2 mg/minute IV infusion OR 20 mg every 10 minutes IV to maximum of 80 mg
7、 every 10 minutes (maximum cumulative dose 300 mg/24 hours) PROPRANOLOL HYDROCHLORIDE Adults: 10 mg orally 3 times daily initially, increase dose as necessary to maximum of 80 mg 3 times daily Pediatrics: 1 to 2 mg/kg orally twice daily (maximum 15 mg/kg/day) ESMOLOL HYDROCHLORIDE,SODIUM NITROPRUSSI
8、DE Adults (Following initial phentolamine therapy): 0.3 to 0.5 mcg/kg/minute IV; increase in increments of 0.5 mcg/kg/minute to desired effect (range 0.5 to 10 mcg/kg/minute) Pediatrics (Following initial phentolamine therapy): 0.3 to 0.5 mcg/kg/minute IV; increase in increments of 0.5 mcg/kg/minute
9、 to desired effect (range 0.5 to 10 mcg/kg/minute),NIFEDIPINE Adults: 10 to 20 mg orally 3 times daily OR 30 to 60 mg orally once daily,Selective alpha1-blocking agents, such as prazosin, terazosin, and doxazosin, are altermative medications when long-term therapy is required for metastatic pheochro
10、mocytoma.,Treatment,Negative side-effects might be tachycardia, orthostatic hypotension, gastrointestinal problems or swelling of nasal mucosa due to effective a-blockage.BBs should be added, as needed, to control tachycardia and arrhythmia. 8 CCBs may also be advantageous as secondary or tertiary a
11、gents because they attenuate the pressor response to norepinephrine and can prevent catecholamine-induced coronary spasm8,Treatment,Calcium channel blockers have been used alone or with selective a1-receptor blockers to successfully control BP and symptoms in patients with PHEO14Hypertensive crises
12、are controlled with nitroprusside, nitroglycerine, phentolamine or urapidile.13,MICROMEDEX,-blocker僅能用於已經在使用-blocker控制的病患，因為若單獨使用-blocker時，會對骨骼肌血管-mediated vasodilatation產生結抗作用而造成血壓之增高。通常-blocker的使用時機，是在已使用-blocker控制的病患發生心搏過速時，此時可使用propranolol 10mg 一天三至四次11 Monotherapy with doxazosin was effective i
13、n 8 of 12 patients (66.7%), and combined therapy with a beta-blocker was effective in 11 of 12 patients (91.7%).In patients with pheochromocytoma, doxazosin (1 to 2 milligrams (mg) initially, increasing to a dose of 2 to16 mg daily) alone or in combination with a beta-blocker is effective for contro
14、lling blood pressure and heart rate before and during surgery.,Pheochromocytoma,FDA Approval: Adult, no; Pediatric, no Efficacy: Adult, Evidence favors efficacy Recommendation: Adult, Class IIb Strength of Evidence: Adult, Category B,Conclusion,-blockers仍舊是最廣泛被使用的降壓藥，一般常用phenoxybenzamine，但是其會增加catec
15、holamines和metanephrine的合成，使得心跳加快 .7 Despite adverse side effects, phenoxybenzamine has been widely used for the preoperative management of patients with pheochromocytoma. Doxazosin (2-16 mg/day) was as effective as phenoxybenzamine in controlling arterial pressure and heart rate before and during su
16、rgery, but doxazosin, a specific a 1-adrenoceptor antagonist, caused fewer undesirable side effects both before and after surgery. 6 Pheochromocytomas with mild or moderate level of blood pressure are indicative of the use of doxazosin mosylate .8,Conclusion,Once a phaeochromocytoma is located, comp
17、lications during surgery need to be kept to a minimum by appropriate preoperative medical treatment. The major aim of medical pretreatment is to prevent catecholamine induced, serious, and potentially life-threatening complications during surgery, including hypertensive crises, cardiac arrhythmias,
18、pulmonary oedema, and cardiac ischaemia.12 Should substantial rises in blood pressure still take place during surgery, these can be controlled by bolus or by continuous infusion of phentolamine, sodium nitroprusside, or a shortacting calcium antagonist (eg, nicardipine); tachyarrhythmias can be trea
19、ted by infusion of a shortacting -adrenoceptor blocker (eg, esmolol). 12,Conclusion,Selective postsynaptica1-receptor antagonists, such as prazosin, terazosin, and doxazosin, have a shorter duration of action, permitting more rapid adjustment of dosage and a reduced duration of postoperative hypoten
20、sion.,Graham JB. Pheochromocytoma and hypertension; An analysis of 207 cases. Int Surg 1951;92:105-21. Y-C Kuo, M-Y Yen, Y-F Yang, et al. Pheochromocytoma with acute manifestation at the emergency department: a case report. J Taiwan Emerg Med 2002; 4:129-135.Walther MM, Keiser HR, Linehan WM. Pheoch
21、romocytoma: evaluation, diagnosis, and treatment. World J Urol 1999;17:35-9. Sheng-Wen Cheng, Ying-Hock Teng, Chao-Hsin Wu, Chen-Kuo Chu, Lee-Min Wang. Pheochromocytoma Presenting as a Cutaneous Manifestation: A Case Report. J Taiwan Emerg Med 2008;10:87-90 Jia-Hwia Wang. Pheochromocytoma. JTUA 20:7
22、5-8, 2009 Prys-Roberts C, Farndon JR. Efficacy and safety of doxazosin for perioperative management of patients with pheochromocytoma. World J Surg. 2002 Aug;26(8):1037-42. Epub 2002 Jun 19.Case Discussion 內科繼續教育 Pan DL, Li HZ, Ji ZG, Zeng ZP. Effects of doxazosin mosylate and phenoxybenzamine in pr
23、eoperative volume expansion of pheochromocytoma: a comparative study in 38 cases . Zhonghua Yi Xue Za Zhi. 2005 Jun 1;85(20):1403-5. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE DIAGNOSIS AND TREATMENT OF HYPERTENSION AACE Hypertension Guidelines
24、, Endocr Pract. 2006;12 Neuroendocrine Tumors. Practice Guidelines in Oncology v.1.2010,Reference,Reference,Chung-Yin Wu, Eric Chen, Gien-Wen Chio. Severe Hypertension Induced by Pheochromocytoma: A Case Report and Review of Literature. J Emerg Crit Care Med. Vol.10, No.3, 1999 Jacques W M Lenders,
25、Graeme Eisenhofer, Massimo Mannelli, Karel Pacak. Phaeochromocytoma. Vol 366 August 20, 2005 Nicole Reischa, Mariola Peczkowskab, Andrzej Januszewiczb and Hartmut P.H. Neumannc. Pheochromocytoma: presentation, diagnosis and treatment. 2332 Journal of Hypertension 2006, Vol 24 No 12 Asterios Karagiannis, Dimitri P Mikhailidis1, Vasilios G Athyros and Faidon Harsoulis. Pheochromocytoma: an update on genetics and management. Endocrine-Related Cancer (2007) 14 935956,Thanks for You,
