ナトリウムチャネル遮断薬

WordNet

a three-dimensional shape with six square or rectangular sides (同)cube
(computer science) a sector or group of sectors that function as the smallest data unit permitted; "since blocks are often defined as a single sector, the terms `block and `sector are sometimes used interchangeably"
support, secure, or raise with a block; "block a plate for printing"; "block the wheels of a car"
a solid piece of something (usually having flat rectangular sides); "the pyramids were built with large stone blocks"
housing in a large building that is divided into separate units; "there is a block of classrooms in the west wing"
a rectangular area in a city surrounded by streets and usually containing several buildings; "he lives in the next block" (同)city block
an inability to remember or think of something you normally can do; often caused by emotional tension; "I knew his name perfectly well but I had a temporary block" (同)mental_block
a number or quantity of related things dealt with as a unit; "he reserved a large block of seats"; "he held a large block of the companys stock"
interrupt the normal function of by means of anesthesia; "block a nerve"; "block a muscle"
run on a block system; "block trains"
shape by using a block; "Block a hat"; "block a garment"
shape into a block or blocks; "block the graphs so one can see the results clearly"
stamp or emboss a title or design on a book with a block; "block the book cover"
direct the flow of; "channel information towards a broad audience" (同)canalize, canalise
a television station and its programs; "a satellite TV channel"; "surfing through the channels"; "they offer more than one hundred channels" (同)television channel, TV channel
a passage for water (or other fluids) to flow through; "the fields were crossed with irrigation channels"; "gutters carried off the rainwater into a series of channels under the street"
(often plural) a means of communication or access; "it must go through official channels"; "lines of communication were set up between the two firms" (同)communication channel, line
a path over which electrical signals can pass; "a channel is typically what you rent from a telephone company" (同)transmission channel
a deep and relatively narrow body of water (as in a river or a harbor or a strait linking two larger bodies) that allows the best passage for vessels; "the ship went aground in the channel"
a silvery soft waxy metallic element of the alkali metal group; occurs abundantly in natural compounds (especially in salt water); burns with a yellow flame and reacts violently in water; occurs in sea water and in the mineral halite (rock salt) (同)Na, atomic number 11
a class of drugs that inhibit (block) some biological process (同)blocking_agent
a football player whose responsibility is to block players attempting to stop an offensive play
official routes of communication; "you have to go through channels"

PrepTutorEJDIC

(木・石などの,通例平らな面のある)『かたまり』 / 《米》(四団を街路に囲まれた)『区画』,街区 / 街区の1辺の距離(一般に40メートル前後) / 《英》ブロック(アパート・事務所・商店などに区切られている大きな建物) / 『妨害物』,障害物(obstacle);(障害によって生じた)停滞,渋滞 / 台木,台(まないた・肉切り台・まき割り台・せり売り台・帽子の木型など);《the~》炭頭台 / (特にアメリカンフットボールで)ブロック(相手の選手の突進を阻止する) / 滑車(pulley) / (座席券・株券などの)一組《+『of』+『名』》 / 〈通路など〉'を'『ふさぐ』,〈通行・進行など〉'を'妨げる / 〈帽子など〉の型取りをする / (特にアメリカンフットボールで)〈相手選手の突進〉'を'ブロックする;(ボクシングで)〈相手のパンチ〉'を'ブロックする
〈C〉『水路』(川・湾・運河の船の通行ができる深い部分) / 〈U〉河床・川底 / 〈C〉『海峡』 / 〈C〉みぞ(groove),(道路の)水渠(すいきょ) / 《複数形で》(運搬・伝達の)正式の経路(手続き);(一般に)経路 / 〈C〉(テレビ・ラジオの)チャンネル / …‘に'水路を開く / …‘に'みぞを堀る / …'を'伝える,流す
ソジウム,ナトリウム(金属元素;化学記号はNa)

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/12/19 20:22:40」(JST)

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[Wiki en表示]

Sodium channel blockers are agents that impair conduction of sodium ions (Na⁺) through sodium channels.^[1]

Extracellular[edit]

The following naturally produced substances block sodium channels by binding to and occluding the extracellular pore opening of the channel:

Alkaloid based toxins
- saxitoxin (STX)
- neosaxitoxin (NSTX)
- tetrodotoxin (TTX)

Intracellular[edit]

Drugs which block sodium channels by blocking from the intracellular side of the channel include:

Local anesthetics
Class I antiarrhythmic agents
Some anticonvulsants

Unknown mechanism[edit]

Calcium has been shown to block sodium channels^[2] which explains the effects of hypercalcemia and hypocalcemia.

Caffeine has been shown to inhibit Na⁺ current in ventricular cells of guinea pigs.^[3]

A-803467: specific blockade of Na_v1.8 channels (SCN10A), developed by Icagen and Abbott Laboratories^[4]

Antiarrhythmic[edit]

Sodium channel blockers are used in the treatment of cardiac arrhythmia. They are classified as "Type I" in the Vaughan Williams classification.

Class I antiarrhythmic agents interfere with the (Na⁺) channel. Class I agents are grouped by their effect on the Na⁺ channel, and by their effect on cardiac action potentials. Class I agents are called Membrane Stabilizing Agents. 'Stabilizing' refers to the decrease of excitogenicity of the plasma membrane effected by these agents. A few class II agents, propranolol for example, also have a membrane stabilizing effect.

Class Ia agents[edit]

Class Ia agent decreasing V_max, thereby increasing action potential duration.

Class Ia agents block the fast sodium channel, which depresses the phase 0 depolarization (i.e. reduces V_max), which prolongs the action potential duration by slowing conduction. Agents in this class also cause decreased conductivity and increased refractoriness.

Indications for Class Ia agents are supraventricular tachycardia, ventricular tachycardia, symptomatic ventricular premature beats, and prevention of ventricular fibrillation.

Procainamide can be used to treat atrial fibrillation in the setting of Wolff-Parkinson-White syndrome, and to treat wide complex hemodynamically stable tachycardias. Oral procainamide is no longer being manufactured in the US, but intravenous formulations are still available.

While procainamide and quinidine may be used in the conversion of atrial fibrillation to normal sinus rhythm, they should only be used in conjunction with an AV node blocking agent such as digoxin or verapamil, or a beta blocker), because procainamide and quinidine can increase the conduction through the AV node and may cause 1:1 conduction of atrial fibrillation, causing an increase in the ventricular rate.

Class Ia agents include quinidine, procainamide and disopyramide.

Class Ib agents[edit]

Effect of class Ib antiarrhythmic agents on the cardiac action potential.

Class Ib antiarrhythmic agents are sodium channel blockers. They have fast onset and offset kinetics, meaning that they have little or no effect at slower heart rates, and more effects at faster heart rates. Class Ib agents shorten the action potential duration and reduce refractoriness. These agents will decrease V_max in partially depolarized cells with fast response action potentials. They either do not change the action potential duration, or they may decrease the action potential duration. Class Ib drugs tend to be more specific for voltage gated Na channels than Ia. Lidocaine in particular is highly frequency dependent, in that it has more activity with increasing heart rates. This is because lidocaine selectively blocks Na channels in their open and inactive states and has little binding capability in the resting state.

Class Ib agents are indicated for the treatment of ventricular tachycardia and symptomatic premature ventricular beats, and prevention of ventricular fibrillation.

Class Ib agents include lidocaine, mexiletine, tocainide, and phenytoin.

Class Ic agents[edit]

Effect of class Ic antiarrhythmic agent on cardiac action potential.

Class Ic antiarrhythmic agents markedly depress the phase 0 depolarization (decreasing V_max). They decrease conductivity, but have a minimal effect on the action potential duration. Of the sodium channel blocking antiarrhythmic agents (the class I antiarrhythmic agents), the class Ic agents have the most potent sodium channel blocking effects.

Class Ic agents are indicated for life-threatening ventricular tachycardia or ventricular fibrillation, and for the treatment of refractory supraventricular tachycardia (i.e. atrial fibrillation). These agents are potentially pro-arrhythmic, especially in settings of structural heart disease (e.g. post-myocardial infarction), and are contraindicated in such settings.

Class Ic agents include encainide, flecainide, moricizine, and propafenone. Encainide is not available in the US.

Other uses[edit]

Sodium channel blockers are also used as local anesthetics and epilepsy treatments.^[5]

Sodium channel blockers have been proposed for use in the treatment of cystic fibrosis,^[6] but current evidence is mixed.^[7]

It has been suggested that the analgesic effect of some antidepressants is due to sodium channel blockade.^[8]

References[edit]

^ Sodium Channel Blockers at the US National Library of Medicine Medical Subject Headings (MeSH)
^ Cota (1999). "Calcium block of Na+ channels and its effect on closing rate". Proceedings of the National Academy of Sciences of the United States of America 96 (7): 4154–4157. Bibcode:1999PNAS...96.4154A. doi:10.1073/pnas.96.7.4154. PMC 22436. More than one of |author= and |last= specified (help)
^ Habuchi Y, Tanaka H, Furukawa T, Tsujimura Y (Dec 1991). "Caffeine-induced block of Na⁺ current in guinea pig single ventricular cells". Am J Physiol. 261 (6 Pt 2): H1855–63. PMID 1661092.
^ Jarvis, Michael F.; Prisca Honore and 35 additional coauthors (2007-05-27). "A-803467, a potent and selective Na_v1.8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the rat". PNAS (National Academy of Sciences of the United States) 104 (20): 8520–5. doi:10.1073/pnas.0611364104. PMC 1895982. PMID 17483457. Retrieved 2007-12-16.
^ Wood JN, Boorman J (2005). "Voltage-gated sodium channel blockers; target validation and therapeutic potential". Curr Top Med Chem 5 (6): 529–37. doi:10.2174/1568026054367584. PMID 16022675.
^ Hirsh AJ, Zhang J, Zamurs A, et al. (April 2008). "Pharmacological properties of N-(3,5-diamino-6-chloropyrazine-2-carbonyl)-N'-4-[4-(2,3-dihydroxypropoxy)phenyl]butyl-guanidine methanesulfonate (552-02), a novel epithelial sodium channel blocker with potential clinical efficacy for cystic fibrosis lung disease". J. Pharmacol. Exp. Ther. 325 (1): 77–88. doi:10.1124/jpet.107.130443. PMID 18218832.
^ "Sodium channel blockers for cystic fibrosis".
^ Dick IE, Brochu RM, Purohit Y, Kaczorowski GJ, Martin WJ, Priest BT (April 2007). "Sodium channel blockade may contribute to the analgesic efficacy of antidepressants". J Pain 8 (4): 315–24. doi:10.1016/j.jpain.2006.10.001. PMID 17175203.

UpToDate Contents

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1. 心筋活動電位および抗不整脈剤の作用 myocardial action potential and action of antiarrhythmic drugs
2. ブルガダ症候群および突然の心停止 brugada syndrome
3. 不整脈治療におけるカルシウムチャネル遮断剤拮抗剤 calcium channel blockers in the treatment of cardiac arrhythmias
4. 腎集合管ナトリウムチャンネルの遺伝的障害：リドル症候群および偽性低アルドステロン症1型 genetic disorders of the collecting tubule sodium channel liddles syndrome and pseudohypoaldosteronism type 1
5. 小児蘇生法における第一選択剤 primary drugs in pediatric resuscitation

English Journal

Activation of the prelimbic medial prefrontal cortex induces anxiety-like behaviors via N-Methyl-D-aspartate receptor-mediated glutamatergic neurotransmission in mice.

Saitoh A1, Ohashi M, Suzuki S, Tsukagoshi M, Sugiyama A, Yamada M, Oka J, Inagaki M, Yamada M.
Journal of neuroscience research.J Neurosci Res.2014 Aug;92(8):1044-53. doi: 10.1002/jnr.23391. Epub 2014 Apr 21.
We investigated the possible roles of the prelimbic medial prefrontal cortex (PL) in the regulation of anxiety-like behaviors by pharmacologically activating the terminals of neuronal inputs or postsynaptic efferent neurons with a sodium channel activator veratrine. The extracellular glutamate level
PMID 24752881

Antiarrhythmic drugs and epilepsy.

Borowicz KK1, Banach M2.
Pharmacological reports : PR.Pharmacol Rep.2014 Aug;66(4):545-551. doi: 10.1016/j.pharep.2014.03.009. Epub 2014 Apr 13.
For a long time it has been suspected that epilepsy and cardiac arrhythmia may have common molecular background. Furthermore, seizures can affect function of the central autonomic control centers leading to short- and long-term alterations of cardiac rhythm. Sudden unexpected death in epilepsy (SUDE
PMID 24948053

Risk stratification and treatment of brugada syndrome.

Arbelo E1, Brugada J.
Current cardiology reports.Curr Cardiol Rep.2014 Jul;16(7):508. doi: 10.1007/s11886-014-0508-1.
The Brugada syndrome (BS) is a hereditary disease characterized by typical electrocardiographic alterations (elevation of the ST segment in right precordial leads) that affects young individuals without structural heart disease, predisposing them to ventricular arrhythmias and sudden death (SD). Sev
PMID 24893941

Japanese Journal

Effects of gomisin A on vascular contraction in rat aortic rings

Seok Young Mi,Choi Young Whan,Kim Gyung-Duck,Kim Hye Young,Takuwa Yoh,Kim In Kyeom
Naunyn-Schmiedeberg's Archives of Pharmacology 383(1), 45-56, 2011-01
… Pretreatment with GA dose-dependently inhibited the concentration-response curves in response to sodium fluoride (NaF) or thromboxane A2 agonist U46619, but not to phorbol 12, 13-dibutyrate (PDBu). … However, K+ channel blockers such as glibenclamide, apamin, or charybdotoxin did not affect the vascular relaxation induced by GA. …
NAID 120002829317

Effects of gomisin A on vascular contraction in rat aortic rings

Seok Young Mi,Choi Young Whan,Kim Gyung-Duck,Kim Hye Young,Takuwa Yoh,Kim In Kyeom
Naunyn-Schmiedeberg's Archives of Pharmacology 383(1), 45-56, 2011-01
… Pretreatment with GA dose-dependently inhibited the concentration-response curves in response to sodium fluoride (NaF) or thromboxane A2 agonist U46619, but not to phorbol 12, 13-dibutyrate (PDBu). … However, K+ channel blockers such as glibenclamide, apamin, or charybdotoxin did not affect the vascular relaxation induced by GA. …
NAID 120002754121