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Revision as of 12:21, 6 December 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,084 edits Saving copy of the {{drugbox}} taken from revid 464348071 of page Quinidine for the Chem/Drugbox validation project (updated: 'DrugBank', 'ChEMBL').		Latest revision as of 19:11, 13 December 2024 edit 2603:6000:8700:824:9181:dcc9:a723:8e8e (talk) →History: Spelling correctionTags: Mobile edit Mobile app edit Android app edit App section source
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			{{Short description|Antiarrythmic medication}}
	{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
			{{Distinguish|quinine|quifenadine}}
	{{Drugbox		{{Drugbox
	| Verifiedfields = changed		| Verifiedfields = changed
			| Watchedfields = changed
	| verifiedrevid = 408381751
			| verifiedrevid = 464378674
	| IUPAC_name = (9''S'')-6'-methoxycinchonan- 9-ol
			| IUPAC_name = (''S'')-(6-Methoxyquinolin-4-yl)methanol
	| image = quinidine2d.png
	| image2 = Quinidine-3d-balls.png		| image = Quinidine structure.png
	<!--Clinical data-->		<!--Clinical data-->
	| tradename =		| tradename = Quinaglute, Quinidex
	| Drugs.com = {{drugs.com|monograph|quinidine-sulfate}}		| Drugs.com = {{drugs.com|monograph|quinidine-sulfate}}
			| pregnancy_AU = C
	| routes_of_administration = Oral
			| pregnancy_US = C
			| legal_AU = S4
			| legal_CA = Rx-only
			| legal_UK = POM
			| legal_US = Rx-only
			| routes_of_administration = ], ], ]
	<!--Pharmacokinetic data-->		<!--Pharmacokinetic data-->
	| bioavailability = 70-80%		| bioavailability = 70–85%
	| metabolism = 50-90% ]		| metabolism = 50–90% (by ])
	| elimination_half-life = 6-8h		| elimination_half-life = 6–8 hours
	| excretion = ]		| excretion = By the liver (20% as unchanged quinidine via urine)
	<!--Identifiers-->		<!--Identifiers-->
	| CASNo_Ref = {{cascite|correct|CAS}}
	| CAS_number_Ref = {{cascite|correct|??}}		| CAS_number_Ref = {{cascite|correct|??}}
	| CAS_number = 56-54-2		| CAS_number = 56-54-2
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	| ATC_suffix = BA01		| ATC_suffix = BA01
	| PubChem = 441074		| PubChem = 441074
			| IUPHAR_ligand = 2342
	| DrugBank_Ref = {{drugbankcite|correct|drugbank}}		| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
	| DrugBank = DB00908		| DrugBank = DB00908
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}		| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 389880		| ChemSpiderID = 389880
			| KEGG_Ref = {{keggcite|changed|kegg}}
			| KEGG = D08458
	| UNII_Ref = {{fdacite|correct|FDA}}		| UNII_Ref = {{fdacite|correct|FDA}}
	| UNII = ITX08688JL		| UNII = ITX08688JL
	| ChEBI_Ref = {{ebicite|changed|EBI}}		| ChEBI_Ref = {{ebicite|correct|EBI}}
	| ChEBI = 28593		| ChEBI = 28593
	| ChEMBL_Ref = {{ebicite|changed|EBI}}		| ChEMBL_Ref = {{ebicite|changed|EBI}}
	| ChEMBL = <!-- blanked - oldvalue: 97 -->		| ChEMBL = 97
	| C=20 | H=24 | N=2 | O=2
			<!--Chemical data-->
	| molecular_weight = 324.417 g/mol
			| C=20 | H=24 | N=2 | O=2
	| smiles = O(c4cc1c(nccc1(O)2N3CC(C2)(/C=C)C3)cc4)C
			| SMILES = O(c4cc1c(nccc1(O)2N3CC(C2)(/C=C)C3)cc4)C
	| InChI = 1/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
	| InChIKey = LOUPRKONTZGTKE-LHHVKLHABX
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 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		| StdInChI = 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
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}		| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChIKey = LOUPRKONTZGTKE-LHHVKLHASA-N		| StdInChIKey = LOUPRKONTZGTKE-LHHVKLHASA-N
	| synonyms = (2-ethenyl- 4-azabicyclo oct- 5-yl)- (6-methoxyquinolin- 4-yl)- methanol,<br/>		| synonyms = (2-Ethenyl-4-azabicyclooct-5-yl)-(6-methoxyquinolin-4-yl)-methanol
	}}		}}
			'''Quinidine''' is a ] used to treat heart rhythm disturbances.<ref name="pmid9414330">{{cite journal | vauthors = Grace AA, Camm AJ | title = Quinidine | journal = The New England Journal of Medicine | volume = 338 | issue = 1 | pages = 35–45 | date = January 1998 | pmid = 9414330 | doi = 10.1056/NEJM199801013380107 }}</ref> It is a ] of ] ],<ref name="pmid32110303">{{cite journal | vauthors = Shiomi S, Misaka R, Kaneko M, Ishikawa H | title = Enantioselective total synthesis of the unnatural enantiomer of quinine | journal = Chemical Science | volume = 10 | issue = 41 | pages = 9433–9437 | date = November 2019 | pmid = 32110303 | doi = 10.1039/c9sc03879e| pmc = 7020653 }}</ref> originally derived from the bark of the ] tree. The drug causes increased ] duration, as well as a prolonged ]. As of 2019, its IV formulation is no longer being manufactured for use in the United States.<ref name="CDC2019">{{cite web |title= Artesunate Now First-Line Treatment for Severe Malaria in the United States | work = CDC Online Newsroom | publisher = U.S. Centers for Disease Control and Prevention |url=https://www.cdc.gov/media/releases/2019/s0328-artesunate-first-line-treatment.html |access-date=6 April 2019 |language=en-us |date=28 March 2019}}</ref>{{TOC limit}}
			==Medical uses==
			Quinidine is occasionally used as a ] to prevent ]s, particularly in ], although its safety in this indication is uncertain.<ref name="pmid9414330"/><ref>{{cite journal | vauthors = Bozic B, Uzelac TV, Kezic A, Bajcetic M | title = The Role of Quinidine in the Pharmacological Therapy of Ventricular Arrhythmias 'Quinidine' | journal = Mini Reviews in Medicinal Chemistry | volume = 18 | issue = 6 | pages = 468–475 | date = 2018 | pmid = 28685701 | doi = 10.2174/1389557517666170707110450 }}</ref>
			It reduces the recurrence of ] after patients undergo ], but it has ] effects and trials suggest that it may lead to an overall increased mortality in these patients.<ref>{{cite journal | vauthors = Valembois L, Audureau E, Takeda A, Jarzebowski W, Belmin J, Lafuente-Lafuente C | title = Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | issue = 9 | pages = CD005049 | date = September 2019 | pmid = 31483500 | pmc = 6738133 | doi = 10.1002/14651858.CD005049.pub5 }}</ref>
			Quinidine is also used to treat ].<ref name="pmid17521305">{{cite journal | vauthors = Kaufman ES | title = Quinidine in short QT syndrome: an old drug for a new disease | journal = Journal of Cardiovascular Electrophysiology | volume = 18 | issue = 6 | pages = 665–666 | date = June 2007 | pmid = 17521305 | doi = 10.1111/j.1540-8167.2007.00815.x | s2cid = 42247356 }}</ref>
			Eli Lilly has discontinued manufacture of parenteral quinidine gluconate in the US, and its future availability in many countries is uncertain.<ref>{{Cite web | url=https://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Quinidine+Gluconate+Injection&st=d&tab=tabs-2 | archive-url = https://web.archive.org/web/20190322143419/https://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Quinidine+Gluconate+Injection&st=d&tab=tabs-2 | archive-date = 22 March 2019 |title = Quinidine Gluconate Injection | work = FDA: Drug Shortages | publisher = U.S. Food and Drug Administration | date = 1 December 2017 }}</ref>
			===Other uses===
			There is one study supporting the use of a novel combination of ] and low dose quinidine in alleviating symptoms of easy laughing and crying (]); these are a type of rather severe uncontrollable behaviors which can be present in various neurological pathologies such as ] and ]. The dose of quinidine (10&nbsp;mg two times daily) is about 1/40th of a relatively low antiarrhythmic dose (400&nbsp;mg, twice or 3 times daily, as an example; antiarrhythmic doses can sometimes exceed 1500&nbsp;mg/day). The authors did not observe significant safety risks using the low quinidine dose, but urged caution and also pointed out that quinidine interacts with a large number of other medications in dangerous or unpredictable ways. A meta analysis was published referencing only that one study.<ref>{{cite journal | vauthors = Kongpakwattana K, Sawangjit R, Tawankanjanachot I, Bell JS, Hilmer SN, Chaiyakunapruk N | title = Pharmacological treatments for alleviating agitation in dementia: a systematic review and network meta-analysis | journal = British Journal of Clinical Pharmacology | volume = 84 | issue = 7 | pages = 1445–1456 | date = July 2018 | pmid = 29637593 | pmc = 6005613 | doi = 10.1111/bcp.13604 }}</ref><ref name="D+Q Trial">{{cite journal | vauthors = Brooks BR, Thisted RA, Appel SH, Bradley WG, Olney RK, Berg JE, Pope LE, Smith RA | display-authors = 6 | title = Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a randomized trial | journal = Neurology | volume = 63 | issue = 8 | pages = 1364–1370 | date = October 2004 | pmid = 15505150 | doi = 10.1212/01.wnl.0000142042.50528.2f | s2cid = 25732335 }}</ref>
			Although intravenous quinidine is sometimes used to treat '']'' ], the future availability of this agent is uncertain.<ref>{{Cite web | url=https://www.cdc.gov/malaria/new_info/2017/Quinidine_2017.html |title = Quinidine Availability in the United States | work = U.S. Centers for Disease Control and Prevention |date = 2019-01-28}}</ref>
			==Side effects==
			Quinidine is an inhibitor of the ] enzyme ], and can lead to increased blood levels of ], ], ], and some ]. Quinidine also inhibits the ] ] and so can cause some peripherally acting drugs such as ] to have central nervous system side effects, such as respiratory depression, if the two drugs are coadministered.<ref name="pmid11014404">{{cite journal | vauthors = Sadeque AJ, Wandel C, He H, Shah S, Wood AJ | title = Increased drug delivery to the brain by P-glycoprotein inhibition | journal = Clinical Pharmacology and Therapeutics | volume = 68 | issue = 3 | pages = 231–237 | date = September 2000 | pmid = 11014404 | doi = 10.1067/mcp.2000.109156 | s2cid = 38467170 }}</ref>
			Quinidine can cause thrombocytopenia, granulomatous hepatitis, ], and '']'' (dangerous heart rhythm),<ref>{{cite book |last1=Dubin DB |title=Rapid interpretation of EKG's: an interactive course |date=2000 |publisher=Cover Publishing Company |location=Tampa, Fla |isbn=978-0-912912-06-6 |edition=6th}}</ref> and has been largely phased out in favor of other antiarrhythmics. ''Torsades'' can occur after the first dose. Quinidine-induced ] (low platelet count) is mediated by the ], and may lead to thrombocytic ].
			Quinidine intoxication can lead to a collection of symptoms collectively known as ], with ] (ringing in the ears) being among the most characteristic and common symptoms of this toxicity syndrome.
			==Pharmacology==
			===Pharmacodynamics===
			Quinidine acts as a ] of ]s.<ref name="pmid25927480">{{cite journal | vauthors = de Lera Ruiz M, Kraus RL | title = Voltage-Gated Sodium Channels: Structure, Function, Pharmacology, and Clinical Indications | journal = Journal of Medicinal Chemistry | volume = 58 | issue = 18 | pages = 7093–7118 | date = September 2015 | pmid = 25927480 | doi = 10.1021/jm501981g | doi-access = free }}</ref><ref name="Abriel2015">{{cite book| vauthors = Roden DM | chapter = Pharmacology and Toxicology of Na<sub>V</sub>1.5 Class 1 Antiarrhythmic Drugs | veditors = Abriel H |title=Cardiac Sodium Channel Disorders, An Issue of Cardiac Electrophysiology Clinics, E-Book| chapter-url = https://books.google.com/books?id=vnKPBQAAQBAJ&pg=PA695|date=1 September 2015|publisher=Elsevier Health Sciences|isbn=978-0-323-32641-4|pages=695–}}</ref> Inhibition of the ] channel is specifically involved in its antiarrhythmic effects as a class I antiarrhythmic agent.<ref name="HemmingsEgan2013">{{cite book | vauthors = Abbott GW, Levi R | chapter = Antiarrhythmic Drugs | veditors = Hemmings HC, Egan TD |title=Pharmacology and Physiology for Anesthesia: Foundations and Clinical Application: Expert Consult - Online and Print| chapter-url=https://books.google.com/books?id=s8CXrbimviMC&pg=PT451|year=2013|publisher=Elsevier Health Sciences|isbn=978-1-4377-1679-5|pages=451–}}</ref> Quinidine also blocks certain ]s (e.g., ], ], ], among others),<ref name="UrbanPatel2015">{{cite book| vauthors = Pearlstein RA, MacCannell KA, Hu QY, Farid R, Duca JS | chapter = The Mechanistic Basis of hERG Blockade and the Proarrhythmic Effects Thereof | veditors = Urban L, Patel V, Vaz RJ |title=Antitargets and Drug Safety| chapter-url = https://books.google.com/books?id=jkBPCAAAQBAJ&pg=PA303 |date=23 February 2015|publisher=Wiley|isbn=978-3-527-67367-4|pages=303–}}</ref><ref name="ArcherRusch2012">{{cite book | vauthors = Archer SL, Rusch NJ |title=Potassium Channels in Cardiovascular Biology|url=https://books.google.com/books?id=e_gxBwAAQBAJ&pg=PT343|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4615-1303-2|pages=343–}}</ref> acts as an ] and ],<ref name="pmid9570190">{{cite journal | vauthors = Shibata K, Hirasawa A, Foglar R, Ogawa S, Tsujimoto G | title = Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors | journal = Circulation | volume = 97 | issue = 13 | pages = 1227–1230 | date = April 1998 | pmid = 9570190 | doi = 10.1161/01.cir.97.13.1227 | doi-access = free }}</ref> and is an ].<ref name="HemmingsEgan2013" /> It is said to be a ] ] ] ].<ref name="LavradorCabralVeríssimo2023">{{cite journal | vauthors = Lavrador M, Cabral AC, Veríssimo MT, Fernandez-Llimos F, Figueiredo IV, Castel-Branco MM | title = A Universal Pharmacological-Based List of Drugs with Anticholinergic Activity | journal = Pharmaceutics | volume = 15 | issue = 1 | date = January 2023 | page = 230 | pmid = 36678858 | pmc = 9863833 | doi = 10.3390/pharmaceutics15010230 | doi-access = free | url = }}</ref>
			====Mechanism of action====
			Like all other class I ]s, quinidine primarily works by blocking the fast inward ] current (I<sub>Na</sub>). Quinidine's effect on I<sub>Na</sub> 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 ] to decrease (decreased V<sub>max</sub>).
			It seems still efficacious as an IV antimalarial against Plasmodium falciparum. This electrolyte dependent agent also increases action potentials and prolongs the QT interval.
			Quinidine also blocks the slowly inactivating, ]-sensitive ] current, the slow inward ] current (I<sub>Ca</sub>), the rapid (I<sub>Kr</sub>) and slow (I<sub>Ks</sub>) components of the ], the ] (I<sub>KI</sub>), the ] (I<sub>K<sub>ATP</sub></sub>) and I<sub>to</sub>.
			At micromolar concentrations, quinidine inhibits ] by binding to the same receptor sites as the digitalis glycosides such as ].
			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.
			===Pharmacokinetics===
			====Elimination====
			{{unsourced section|date=February 2024}}
			The ] of oral quinidine is 6 to 8&nbsp;hours, and it is eliminated by the ] system in the liver. About 20% is excreted unchanged via the kidneys.
			==History==
			The effects of ] bark (the botanical source from which quinidine is extracted) had been commented on long before the understanding of cardiac physiology arose. ], in his 1749 work on the anatomy, function, and diseases of the heart, had this to say:
			<blockquote>"Long and rebellious palpitations have ceded to this ]".<ref name="ncbi">{{cite journal | vauthors = Hollman A | title = Quinine and quinidine | journal = British Heart Journal | volume = 66 | issue = 4 | pages = 301 | date = October 1991 | pmid = 1747282 | pmc = 1024726 | doi = 10.1136/hrt.66.4.301 }}</ref></blockquote>
			<blockquote>"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 mixed with a little rhubarb."<ref>{{cite journal | vauthors = Bowman IA | title = Jean-Baptiste Sénac and his treatise on the heart | journal = Texas Heart Institute Journal | volume = 14 | issue = 1 | pages = 5–11 | date = March 1987 | pmid = 15227324 | pmc = 324686 }}</ref></blockquote>
			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, quinidine 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, ] saw a man with ]. 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.<ref name="ncbi" />
			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.<ref>{{cite book | vauthors = Sneader W |title=Drug Discovery: A History |url=https://books.google.com/books?id=mYQxRY9umjcC&q=Frey+Berlin+quinidine&pg=PA95 |date=Jun 20, 2005 |publisher=John Wiley and Sons |page=95 |isbn=978-0-471-89980-8}}</ref>
			==Chemistry==
			Quinidine-based ligands are used in AD-mix-β for ].
			==Veterinary use==
			Quinidine sulfate is used in the treatment of atrial fibrillation in horses.<ref>{{cite journal | vauthors = Kurakane E, Amada A |date=1982 |title=Pharmacokinetic Studies on Quinidine Sulfate Orally Administered in Horses |journal=Bulletin of Equine Research Institute |volume=1982 |issue=19 |pages=59–68 |doi=10.11535/jes1977.1982.59 }}</ref><ref>{{cite journal | vauthors = Hiraga A, Sugano S | title = History of research in Japan on electrocardiography in the racehorse | journal = Journal of Equine Science | volume = 26 | issue = 1 | pages = 1–13 | date = 2015 | pmid = 25829865 | pmc = 4379327 | doi = 10.1294/jes.26.1 }}</ref>
			== References ==
			{{Reflist|2}}
			== External links ==
			*
			*
			{{Antiarrhythmic agents}}
			{{Chromalveolate antiparasitics}}
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