Quinaglute

キニジン

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/11/14 07:21:48」(JST)

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Not to be confused with quinine or quifenadine.

Quinidine

Systematic (IUPAC) name
(S)-(6-Methoxyquinolin-4-yl)((2R,4S,8R)-8-vinylquinuclidin-2-yl)methanol
Clinical data
Trade names	Quinaglute, Quinidex
AHFS/Drugs.com	monograph
Pregnancy category	AU: C US: C (Risk not ruled out)
Legal status	AU: Prescription Only (S4) CA: ℞-only UK: Prescription-only (POM) US: ℞-only
Routes of administration	Oral, IM, IV
Pharmacokinetic data
Bioavailability	70-80%
Metabolism	50-90% Hepatic
Biological half-life	6-8h
Excretion	Renal via urine
Identifiers
CAS Registry Number	56-54-2 Y
ATC code	C01BA01
PubChem	CID: 441074
IUPHAR/BPS	2342
DrugBank	DB00908 Y
ChemSpider	389880 Y
UNII	ITX08688JL Y
ChEBI	CHEBI:28593 Y
ChEMBL	CHEMBL97 N
Synonyms	(2-ethenyl- 4-azabicyclo [2.2.2] oct- 5-yl)- (6-methoxyquinolin- 4-yl)- methanol,
Chemical data
Formula	C20H24N2O2
Molecular mass	324.417 g/mol
SMILES O(c4cc1c(nccc1[C@H](O)[C@@H]2N3CC[C@@H](C2)[C@@H](/C=C)C3)cc4)C
InChI InChI=1S/C20H24N2O2/c1-3-13-12-22-9-7-14(13)10-19(22)20(23)16-6-8-21-18-5-4-15(24-2)11-17(16)18/h3-6,8,11,13-14,19-20,23H,1,7,9-10,12H2,2H3/t13-,14-,19+,20-/m0/s1 Y Key:LOUPRKONTZGTKE-LHHVKLHASA-N Y
N (what is this?)  (verify)

Quinidine is a pharmaceutical agent that acts as a class I antiarrhythmic agent (Ia) in the heart. It is a stereoisomer of quinine, originally derived from the bark of the cinchona tree. The drug causes increased action potential duration, as well as a prolonged QT interval.

Mechanism

Like all other class I antiarrhythmic agents, quinidine primarily works by blocking the fast inward sodium current (I_Na). Quinidine's effect on I_Na is known as a 'use dependent block'. This means at higher heart rates, the block increases, while at lower heart rates, the block decreases. The effect of blocking the fast inward sodium current causes the phase 0 depolarization of the cardiac action potential to decrease (decreased V_max).

Quinidine also blocks the slowly inactivating, tetrodotoxin-sensitive Na current, the slow inward calcium current (I_Ca), the rapid (I_Kr) and slow (I_Ks) components of the delayed potassium rectifier current, the inward potassium rectifier current (I_KI), the ATP-sensitive potassium channel (I_KATP) and I_to.

At micromolar concentrations, quinidine inhibits Na⁺/K⁺-ATPase by binding to the same receptor sites as the digitalis glycosides such as ouabain.

The effect of quinidine on the ion channels is to prolong the cardiac action potential, thereby prolonging the QT interval on the surface ECG.

Other ECG effects include a wide notched P wave, wide QRS complex, depressed ST segment, and U waves. These are the results of both slowed depolarization and repolarization.

History

The effects of cinchona bark (the botanical source from which quinidine is extracted) had been commented on long before the understanding of cardiac physiology arose. Jean-Baptiste de Sénac, in his 1749 work on the anatomy, function, and diseases of the heart, had this to say,

"Long and rebellious palpitations have ceded to this febrifuge".

"Of all the stomachic remedies, the one whose effects have appeared to me the most constant and the most prompt in many cases is quinquina [Peruvian bark] mixed with a little rhubarb."

Sénac subsequently became physician to Louis XV of France, a counselor of the state, and superintendent of the mineral waters and medicinals in France. As a result of his influence, throughout the 19th century, quinine was used to augment digitalis therapy. It was described as das Opium des Herzens (the opium of the heart).

However, the use of quinidine to treat arrhythmia really only came into its own because a physician listened to the astute observation of one of his patients. In 1912, Karel Frederik Wenckebach saw a man with atrial fibrillation. He was a Dutch merchant, used to good order in his affairs. He would like to have good order in his heart business, also, and asked, "why there were heart specialists if they could not abolish this very disagreeable phenomenon ... he knew himself how to get rid of his attacks. As I did not believe him, he promised to come back next morning with a regular pulse, and he did."

The man had found by chance that when he took one gram of quinine during an attack, it reliably halted it in 25 minutes; otherwise it would last for two to 14 days. Wenckebach often tried quinine again, but he succeeded in only one other patient.

He made passing mention of it in his book on cardiac arrhythmias published in 1914. Four years later, Walter von Frey of Berlin reported in a leading Viennese medical journal that quinidine was the most effective of the four principal cinchona alkaloids in controlling atrial arrhythmias.

Elimination

The half life of oral quinidine is six to eight hours, and it is eliminated by the cytochrome P450 system in the liver. About 20% is excreted unchanged via the kidneys.

Side effects

Quinidine is also an inhibitor of the cytochrome P450 enzyme 2D6, and can lead to increased blood levels of lidocaine, beta blockers, opioids, and some antidepressants. Quinidine also inhibits the transport protein P-glycoprotein and so can cause some peripherally acting drugs such as loperamide to have central nervous system side effects, such as respiratory depression, if the two drugs are coadministered.

Quinidine can cause thrombocytopenia, granulomatous hepatitis, myasthenia gravis, and torsades de pointes, so is not used much today. Torsades can occur after the first dose. Quinidine-induced thrombocytopenia (low platelet count) is mediated by the immune system, and may lead to thrombocytic purpura.

Quinidine intoxication can lead to a collection of symptoms collectively known as cinchonism, with tinnitus (ringing in the ears) being among the most characteristic and common symptoms of this toxicity syndrome. Quinidine toxicity can also invoke episodes of Torsades de Pointes - a rapid and dangerous ventricular rhythm.

Other uses

A combination of dextromethorphan and quinidine has been shown to alleviate symptoms of easy laughing and crying (pseudobulbar affect) in patients with amyotrophic lateral sclerosis and multiple sclerosis. This drug is marketed as Nuedexta in the United States.

Intravenous quinidine is also indicated for treatment of Plasmodium falciparum malaria. However, quinidine is not considered the first-line therapy for P. falciparum. The recommended treatments for P. falciparum malaria, according to the Toronto Notes 2008, are a combination of either quinine and doxycycline or atovaquone and proguanil (Malarone).

Quinidine sulfate is used in the treatment of atrial fibrillation in horses.

Quinidine-based ligands are used in AD-mix-β for Sharpless asymmetric dihydroxylation.

See also

• Antiarrhythmic agents
• Cardiac action potential

References

External links

• MedlinePlus
• Poisons Information Monograph

English Journal

• Severe Malaria Complicated by G6PD Deficiency in a Pediatric Tanzanian Immigrant.

• Damhoff HN1, Kuhn RJ2, Stadler LP3.
• The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG.J Pediatr Pharmacol Ther.2014 Oct-Dec;19(4):325-34. doi: 10.5863/1551-6776-19.4.325.
• Approximately 1,500 cases of malaria are diagnosed in the United States each year. Most cases are travelers and immigrants returning from parts of the world where malaria transmission occurs. Malaria is the most frequent cause of systemic febrile illness without localizing symptoms in travelers retu
• PMID 25762879

• A case of imported severe plasmodium falciparum malaria in the emergency department and the current role of exchange transfusion treatment.

• Habeeb H1, Ripper JR, Cohen A, Hinfey PB.
• The Journal of emergency medicine.J Emerg Med.2013 Feb;44(2):e211-5. doi: 10.1016/j.jemermed.2012.02.051. Epub 2012 May 18.
• BACKGROUND: The role of exchange transfusion in the management of severe malaria is not well documented in Emergency Medicine literature.OBJECTIVES: The goal of this article is to review the importance of considering malaria in the differential diagnosis of the febrile returned traveler and to discu
• PMID 22609412

• Artesunate: investigational drug for the treatment of severe falciparum malaria in Hawai'i.

• Callender DM1, Hsue G.
• Hawaii medical journal.Hawaii Med J.2011 Apr;70(4):77-9.
• INTRODUCTION: There are hundreds of millions of cases of malaria each year worldwide resulting in a million deaths. These deaths are mostly due to Plasmodium falciparum. The only Federal Drug Administration approved treatment for severe malaria is intravenous quinidine gluconate. Intravenous quinidi
• PMID 21785506

Related Links

• Quinaglute - definition of Quinaglute in the Medical dictionary ...

forum Join the Word of the Day Mailing List For webmasters TheFreeDictionary Google Bing? Word / Article Starts with Ends with Text ... Quin·a·glute (kwĭn′ə-glo o t′) A trademark for the drug quinidine in its gluconate form. Quinaglute,

• Quinaglute | Reference drugs.

Quinaglute Generic Name: quinidine (Oral route, Injection route, Intramuscular route)KWIN-i-deenOverviewSide EffectsInteractionsFor ProfessionalsMore... Oral ... Pregnancy Category Explanation All Trimesters C Animal studies ...

Related Pictures

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★リンクテーブル★

リンク元

「キニジン」

「キニジン」

　　[★]

英

quinidine

化

硫酸キニジン quinidine sulfate、キニジン硫酸塩水和物

商

Quinaglute, Quinidex

関

抗不整脈薬

• 抗不整脈薬
• Ia群

• APD延長

作用機序

• 活動電位の最大分極速度を抑制

活性化および不活性化状態の時にNaチャネルに結合することでチャネルをブロックする。

(低濃度)

自動能を有する細胞の拡張期脱分極を抑制

(通常)

→閾値の増大

→伝導速度の現象　→　刺激伝導を抑制

→不応期の延長

• Kチャネルを抑制し、膜の再分極を起こりにくくする

→　APD延長　→　異所的刺激による期外収縮の発現を抑制

適応

• 上室性・心室性期外収縮、心房細動・粗動、房室結節リエントリー性発作性頻拍