Transcript Pheochromocytoma

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 history
suspect adhesion ileus
Diadetes Mellitus , type 2
Hypertention
Chronic Kidney Disease
Suspected malignant pheochromocytoma
with multiple para-aortic lymph nodes and liver
metastasis.Complicated with fluctuated blood
pressure, peripheral vessel and bowel ischemia
episodes
Lab Data
12
9.8
10
8
5.7
Creatinine
6
(1.1-1.5mg/dL)
4
2
4.1
2
20
08
/3
/2
1
20
10
/4
20 /6
08
/1
20 1/8
08
/1
1/
28
20
09
/1
/7
20
09
/4
20 /3
09
/5
/1
20 9
09
/5
/2
9
20
09
/6
20 /3
09
/6
/1
20 0
09
/6
/1
20 8
09
/8
/1
20 0
10
/3
/2
2
0
2500
2000
2028.27
1500
1000
1835.6
(11.185.5mcg/day)
1213.95
500
0
2008/11/6
Norepinephrine
2009/1/5
2010/3/22
Drug Profile
97/11/24
97/12/24
98/01/06
98/02/11
98/05/04
98/06/25
98/10/05
Insulin glargine
Insulin aspart
Sennoside A+B
Doxazosin 4mg/tab
1# BID
2# BID
Iososrbide mononitrate
60mg/CRtab
1# QD
Amlodipine 5mg/tab
Propranolol 10mg/tab
1# QD
1# BID
1#QID
•BP=132/95 , HR=108
•Increase Doxazosin 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 of 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
1
hypertensive patients were due to pheochromocytoma.
The diagnosis of pheochromocytomas depends mainly upon the
demonstration of catecholamine excess by 24-h urinary
catecholamines and metanephrines or plasma metanephrines.
Pheochromocytoma
α-blocker
PHENOXYBENZAMINE
HYDROCHLORIDE Adults
(initial): 10 mg orally twice
daily; titrate to maintenance;
may increase dose every
other day to 20 to 40 mg
orally 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
β-blocker
LABETALOL
HYDROCHLORIDE Adult
s: 2 mg/minute IV infusion
OR 20 mg every 10
minutes IV to maximum of
80 mg every 10 minutes
(maximum cumulative dose
300 mg/24 hours)
PROPRANOLOL
HYDROCHLORIDE Adult
s: 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
Vasodilator
SODIUM
NITROPRUSSIDE
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 to
desired effect (range 0.5
to 10 mcg/kg/minute)
CCBs
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 pheochromocytoma.
Treatment
 Negative side-effects might be tachycardia, orthostatic
hypotension, gastrointestinal problems or swelling of
mucosa due to effective a-blockage.
nasal
 BBs should be added, as needed, to control tachycardia and
arrhythmia. 8
 CCBs may also be advantageous as secondary or tertiary
agents 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 PHEO14
crises are controlled with nitroprusside,
nitroglycerine, phentolamine or urapidile.13
 Hypertensive
MICROMEDEX



β-blocker僅能用於已經在使用α-blocker控制的病患，因為若單獨
使用β-blocker時，會對骨骼肌血管β-mediated vasodilatation產生
結抗作用而造成血壓之增高。通常β-blocker的使用時機，是在已
使用α-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 in 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
controlling 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
 α-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catecholamines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 surgery, but doxazosin, a
specific a 1-adrenoceptor antagonist, caused fewer
6
undesirable side effects both before and after surgery.
 Pheochromocytomas with mild or moderate level of blood
8
pressure are indicative of the use of doxazosin mosylate .
Conclusion
 Once a phaeochromocytoma is located, complications 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, 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 treated 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 hypotension.
Reference
1.
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4.
5.
6.
7.
8.
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10.
Graham JB. Pheochromocytoma and hypertension; An analysis of 207 cases. Int Surg
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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. Pheochromocytoma: 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.
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Case Discussion 內科繼續教育
Pan DL, Li HZ, Ji ZG, Zeng ZP. [Effects of doxazosin mosylate and
phenoxybenzamine in preoperative volume expansion of pheochromocytoma: a
comparative study in 38 cases] . Zhonghua Yi Xue Za Zhi. 2005 Jun 1;85(20):1403-5.
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GUIDELINES FOR CLINICAL PRACTICE FOR THE DIAGNOSIS AND TREATMENT
OF HYPERTENSION AACE Hypertension Guidelines, Endocr Pract. 2006;12
Neuroendocrine Tumors. Practice Guidelines in Oncology – v.1.2010
Reference
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