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an antihypertensive drug (trade name Apresoline) that dilates blood vessels; used (often with a diuretic) to treat hypertension and congestive heart failure (同)Apresoline
a complex consisting of an organic base in association with hydrogen chloride

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/10/14 23:44:53」(JST)

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Hydralazine (apresoline) is a direct-acting smooth muscle relaxant used to treat hypertension by acting as a vasodilator primarily in arteries and arterioles. By relaxing vascular smooth muscle, vasodilators act to decrease peripheral resistance, thereby lowering blood pressure and decreasing afterload.^[1]

However, this only has a short term effect on blood pressure, as the system will reset to the previous, high blood pressure necessary to maintain pressure in the kidney necessary for natriuresis. The long term effect of antihypertensive drugs comes from their effects on the pressure natriuresis curve.

It belongs to the hydrazinophthalazine class of drugs.^[2]

Mechanism of action[edit]

Hydralazine increases cyclic guanosine monophosphate (cGMP) levels, increasing the activity of protein kinase G (PKG). Active PKG adds an inhibitory phosphate to myosin light-chain kinase (MLCK) – a protein involved in the activation of cross-bridge cycling (i.e. contraction) in smooth muscle. This results in blood vessel relaxation. It dilates arterioles more than veins.^[3]

Hydralazine requires the endothelium to provide NO (nitric oxide.^[4] ) thus only provides the effects of NO in vivo with functional endothelium. It will not work to vasodilate in vitro in an isolated blood vessel.

Activation of hypoxia-inducible factors has been suggested as a mechanism.^[5]

Clinical use[edit]

Hydralazine is not used as a primary drug for treating hypertension because it elicits a reflex sympathetic stimulation of the heart (the baroreceptor reflex). The sympathetic stimulation may increase heart rate and cardiac output, and in patients with coronary artery disease may cause angina pectoris or myocardial infarction.^[1] Hydralazine may also increase plasma renin concentration, resulting in fluid retention. In order to prevent these undesirable side-effects, hydralazine is usually prescribed in combination with a beta-blocker (e.g., propranolol) and a diuretic.^[1] In the UK, labetalol tends to be the first line beta-blocker.

Hydralazine is used to treat severe hypertension, but again, it is not a first-line therapy for essential hypertension. However, hydralazine is the first-line therapy for hypertension in pregnancy, with methyldopa.^[6]

Pre-clinical research[edit]

Multiple sclerosis: Due to its ability to damage myelin nerve sheaths, acrolein may be a factor in the development of multiple sclerosis. Hydralazine, a known scavenger of acrolein, was found to reduce myelin damage and significantly improve behavioral outcomes in a mouse model of multiple sclerosis (experimental autoimmune encephalomyelitis).^[7]

Side effects[edit]

Common side-effects include:

Diarrhea
Compensatory tachycardia due to baroreceptor reflex ->Angina
Headache
Loss of appetite
Nausea or vomiting
Depression
Pounding heartbeat
Vitamin B6 deficiency ^[8]
Drug-Induced Lupus Erythematosus^[9]^[10]
ANCA-associated Vasculitis - Generally MPO-ANCA positive

Patients given hydralazine over a period of six months may develop a lupus-like syndrome or other immune-related diseases that, in general, are reversible with withdrawal.^[1] Hydralazine is differentially acetylated by fast and slow acetylator phenotypes, hence incidence of lupus-like disease in slow acetylators.^{[citation needed]} Rarely, hydrazaline may cause Dyscrasia typically manifested as a type of leukopenia. As such, your physician may request you undergo regular Complete blood count tests. Template:Cite package insert

References[edit]

^ ^a ^b ^c ^d Harvey, Richard A., Pamela A. Harvey, and Mark J. Mycek. Lippincott's Illustrated Reviews: Pharmacology. 2nd ed. Philadelphia: Lipincott, Williams & Wilkins, 2000. 190.
^ Bourreli, B.; Pinaud, M.; Passuti, N.; Gunst, J. P.; Drouet, J. C.; Remi, J. P. (1988). "Additive effects of dihydralazine during enflurane or isoflurane hypotensive anaesthesia for spinal fusion". Canadian Journal of Anaesthesia 35 (3): 242–248. doi:10.1007/BF03010617. PMID 3383316. edit
^ Le, Bhushan and Vasan. First Aid for the USMLE Step 1. 20th Anniv. Ed, 2010.
^ "antihtn". Retrieved 2008-10-05.
^ Knowles HJ, Tian YM, Mole DR, Harris AL (July 2004). "Novel mechanism of action for hydralazine: induction of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and angiogenesis by inhibition of prolyl hydroxylases". Circ. Res. 95 (2): 162–9. doi:10.1161/01.RES.0000134924.89412.70. PMID 15192023.
^ Bhushan, Vikas, Tao T. Lee, and Ali Ozturk. First Aid for the USMLE Step 1. New York: McGraw-Hill Medical, 2007. 251.
^ Leung, G; Sun W, Zheng L, Brookes S, Tully M, Shi R (2010). "Anti-acrolein treatment improves behavioral outcome and alleviates myelin damage in EAE mouse". Neuroscience 173: 150–5. doi:10.1016/j.neuroscience.2010.11.018. PMC 3034379. PMID 21081153.
^ Sanders, Lisa (2010-06-06). "DIAGNOSIS; Dizzying Symptoms". The New York Times.
^ Schoonen WM,et al. Do selected drugs increase the risk of lupus? A matched case-control study. Br J Clin Pharmacol. 2010 Oct;70(4):588-96. doi:10.1111/j.1365-2125.2010.03733.x.
^ Mazari L, Ouarzane M, Zouali M (April 2007). "Subversion of B lymphocyte tolerance by hydralazine, a potential mechanism for drug-induced lupus". Proc. Natl. Acad. Sci. U.S.A. 104 (15): 6317–22. doi:10.1073/pnas.0610434104. PMC 1851062. PMID 17404230.

UpToDate Contents

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1. 収縮能障害による心不全患者におけるヒドララジンおよび硝酸塩による治療 hydralazine plus nitrate therapy in patients with heart failure due to systolic dysfunction
2. 収縮能障害による心不全の治療の概要 overview of the therapy of heart failure due to systolic dysfunction
3. 高血圧緊急症の薬物治療 drug treatment of hypertensive emergencies
4. 薬物誘発性ループス drug induced lupus
5. 高血圧緊急症の治療 treatment of specific hypertensive emergencies

English Journal

How to manage hypertension in pregnancy effectively.

Magee LA, Abalos E, von Dadelszen P, Sibai B, Easterling T, Walkinshaw S; for the CHIPS Study Group.SourceBC Women's Hospital and Heath Centre and the University of British Columbia, 4500 Oak Street, Room D213, Vancouver, BC V6H 3N1, Canada Centro Rosarino De Estudios Perinatales Perinatales (CREP), Pueyrredon 985, 2000 Rosario, Argentina BC Women's Hospital and Health Centre and the University of British Columbia, 4500 Oak Street, Room 2H30, Vancouver, BC V6H 3N1, Canada Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0526 University of Washington, Box 356460, Seattle, WA 98195-6460, USA Fetal Centre, Liverpool Women's NHS Foundation Trust, Crown Street, Liverpool L8 7SS, UK.
British journal of clinical pharmacology.Br J Clin Pharmacol.2011 Sep;72(3):394-401. doi: 10.1111/j.1365-2125.2011.04002.x.
The hypertensive disorders of pregnancy (HDP) are a leading cause of maternal mortality and morbidity in both well and under-resourced settings. Maternal, fetal, and neonatal complications of the HDP are concentrated among, but not limited to, women with pre-eclampsia. Pre-eclampsia is a systemic di
PMID 21545480

A Single-Stranded DNA-Cross-Reactive Immunogenic Epitope of Human Homocysteine-Inducible Endoplasmic Reticulum Protein.

Oka Y, Hirabayashi Y, Ikeda T, Fujii H, Ishii T, Harigae H.SourceDepartment of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan Department of Rheumatology, Yokohama Rosai Hospital, Yokohama, Japan Department of Rheumatology, Hikarigaoka Spellman Hospital, Sendai, Japan.
Scandinavian journal of immunology.Scand J Immunol.2011 Sep;74(3):296-303. doi: 10.1111/j.1365-3083.2011.02572.x.
The mechanism involved in generating anti-DNA antibodies (Abs) remains unclear, as DNA is poorly immunogenic. Molecular mimicry between DNA and non-DNA substances has been implicated as a possible mechanism. We previously reported that homocysteine-inducible endoplasmic reticulum protein (Herp), whi
PMID 21535081

Japanese Journal

Gene expression analysis in rat livers and immune organs treated with isoniazid, phenytoin, hydralazine hydrochloride or chlorpromazine(Proceedings of the 32nd Annual Meeting)

ITO Kazumi,KIYOSAWA Naoki,WATANABE Kyoko,NIINO Noriyo,KANBORI Miyuki,SATO Takayuki,YAMOTO Takashi,MANABE Sunao,MATSUNUMA Naochika
Journal of toxicological sciences 30(Supplement), S115, 2005-10-31
NAID 110004041828

汎用医薬品の好塩基球段階のアレルギー応答に対する影響

久保鈴子,新井俊彦
病院薬学 22(5), 444-448, 1996-10-10
… and a β-blocker, propranolol and an αβ-stimulant, ephedrine hydrochloride were seen to enhance histamine release. … Other drugs tested including NO-producing drugs, nitroglycerin and hydralazine, a Ca^<++> …
NAID 110001799599

Related Pictures

★リンクテーブル★

リンク元	「ヒドララジン」
関連記事	「hydrochloride」

「ヒドララジン」

Hydralazine
Systematic (IUPAC) name
	1-hydrazinylphthalazine
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a682246
Pregnancy cat.	C; Commonly used to treat severe PIH
Legal status	?
Routes	Oral, intravenous
Pharmacokinetic data
Bioavailability	26-55%
Metabolism	Hepatic
Half-life	2-4 hours
Excretion	Renal
Identifiers
CAS number	86-54-4
ATC code	C02DB02
PubChem	CID 3637
DrugBank	DB01275
ChemSpider	3511
UNII	26NAK24LS8
KEGG	D08044
ChEBI	CHEBI:5775
ChEMBL	CHEMBL276832
Chemical data
Formula	C8H8N4
Mol. mass	160.176 g/mol
	SMILES n2nc(c1ccccc1c2)NN;
	InChI InChI=1S/C8H8N4/c9-11-8-7-4-2-1-3-6(7)5-10-12-8/h1-5H,9H2,(H,11,12) ; Key:RPTUSVTUFVMDQK-UHFFFAOYSA-N ;
(what is this?) (verify);

　　[★]

英: hydralazine
同: 塩酸ヒドララジン hydralazine hydrochloride
商: アプレゾリン, Apresoline
関: 降圧薬

降圧薬。血管拡張薬
動脈系に作用。↓後負荷。　⇔硝酸薬
妊婦に適用可能な降圧剤。とりわけ、妊娠中毒症に伴う高血圧に用いる。以前は、メチルドパが使われた。

作用機序

細動脈の血管平滑筋に作用し弛緩させて(血管抵抗↓)、血圧を下げる (SPC.249)

細動脈が拡張するので細動脈血圧が低下

血圧↓→(反射で)心拍数↑、収縮力↑。(β受容体刺激)レニン放出↑ (SPC.249)

特徴

腎血流量増加
(交感神経遮断薬でありがちな)起立性低血圧、射精不能がない (SPC.249)
反射性に心拍量と心拍数が増すので心臓に負担がかかる→β遮断薬との併用で改善 (SPC.249)

普通は利尿薬やβ遮断薬と併用する

副作用

血管拡張に起因する症状：起立性低血圧、頻脈、顔面紅潮、頭痛など
消化気象上：また悪心・嘔吐、食欲不振、下痢など
血液：(長期大量投与)好酸球増加
全身性エリテマトーデス様症状()lupus-like syndrome lupus syndrome

「hydrochloride」

　　[★] 塩酸塩、ハイドロクロライド　

[Harvey-1] Harvey, Richard A., Pamela A. Harvey, and Mark J. Mycek. Lippincott's Illustrated Reviews: Pharmacology. 2nd ed. Philadelphia: Lipincott, Williams & Wilkins, 2000. 190.

[Bourreli1988-2] Bourreli, B.; Pinaud, M.; Passuti, N.; Gunst, J. P.; Drouet, J. C.; Remi, J. P. (1988). "Additive effects of dihydralazine during enflurane or isoflurane hypotensive anaesthesia for spinal fusion". Canadian Journal of Anaesthesia 35 (3): 242–248. doi:10.1007/BF03010617. PMID 3383316. edit

[First_Aid-3] Le, Bhushan and Vasan. First Aid for the USMLE Step 1. 20th Anniv. Ed, 2010.

[urlantihtn-4] "antihtn". Retrieved 2008-10-05.

[pmid15192023-5] Knowles HJ, Tian YM, Mole DR, Harris AL (July 2004). "Novel mechanism of action for hydralazine: induction of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and angiogenesis by inhibition of prolyl hydroxylases". Circ. Res. 95 (2): 162–9. doi:10.1161/01.RES.0000134924.89412.70. PMID 15192023.

[Bhushan-6] Bhushan, Vikas, Tao T. Lee, and Ali Ozturk. First Aid for the USMLE Step 1. New York: McGraw-Hill Medical, 2007. 251.

[7] Leung, G; Sun W, Zheng L, Brookes S, Tully M, Shi R (2010). "Anti-acrolein treatment improves behavioral outcome and alleviates myelin damage in EAE mouse". Neuroscience 173: 150–5. doi:10.1016/j.neuroscience.2010.11.018. PMC 3034379. PMID 21081153.

[8] Sanders, Lisa (2010-06-06). "DIAGNOSIS; Dizzying Symptoms". The New York Times.

[9] Schoonen WM,et al. Do selected drugs increase the risk of lupus? A matched case-control study. Br J Clin Pharmacol. 2010 Oct;70(4):588-96. doi:10.1111/j.1365-2125.2010.03733.x.

[pmid17404230-10] Mazari L, Ouarzane M, Zouali M (April 2007). "Subversion of B lymphocyte tolerance by hydralazine, a potential mechanism for drug-induced lupus". Proc. Natl. Acad. Sci. U.S.A. 104 (15): 6317–22. doi:10.1073/pnas.0610434104. PMC 1851062. PMID 17404230.

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案内

案内

hydralazine hydrochloride