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Quinidine

PubChem CID
441074
Structure
Quinidine_small.png
Quinidine_3D_Structure.png
Molecular Formula
Synonyms
  • quinidine
  • 56-54-2
  • (+)-Quinidine
  • Conquinine
  • Pitayine
Molecular Weight
324.4 g/mol
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Dates
  • Create:
    2005-06-24
  • Modify:
    2025-01-11
Description
Crystals or white powder. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
Quinidine is a cinchona alkaloid consisting of cinchonine with the hydrogen at the 6-position of the quinoline ring substituted by methoxy. It has a role as an alpha-adrenergic antagonist, an antimalarial, an anti-arrhythmia drug, a sodium channel blocker, a muscarinic antagonist, a potassium channel blocker, a P450 inhibitor, an EC 1.14.13.181 (13-deoxydaunorubicin hydroxylase) inhibitor, an EC 3.6.3.44 (xenobiotic-transporting ATPase) inhibitor and a drug allergen. It derives from a hydride of a cinchonan.
Quinidine is a D-isomer of [quinine] present in the bark of the Cinchona tree and similar plant species. This alkaloid was first described in 1848 and has a long history as an antiarrhythmic medication. Quinidine is considered the first antiarrhythmic drug (class Ia) and is moderately efficacious in the acute conversion of atrial fibrillation to normal sinus rhythm. It prolongs cellular action potential by blocking sodium and potassium currents. A phenomenon known as “quinidine syncope” was first described in the 1950s, characterized by syncopal attacks and ventricular fibrillation in patients treated with this drug. Due to its side effects and increased risk of mortality, the use of quinidine was reduced over the next few decades. However, it continues to be used in the treatment of Brugada syndrome, short QT syndrome and idiopathic ventricular fibrillation.
See also: Quinidine Gluconate (has salt form); Quinidine Sulfate (active moiety of); Quinidine bisulfate (is active moiety of) ... View More ...

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Quinidine.png

1.2 3D Conformer

1.3 Crystal Structures

COD records with this CID as component

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

(S)-[(2R,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanol
Computed by Lexichem TK 2.7.0 (PubChem release 2024.11.20)

2.1.2 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
Computed by InChI 1.07.0 (PubChem release 2024.11.20)

2.1.3 InChIKey

LOUPRKONTZGTKE-LHHVKLHASA-N
Computed by InChI 1.07.0 (PubChem release 2024.11.20)

2.1.4 SMILES

COC1=CC2=C(C=CN=C2C=C1)[C@@H]([C@H]3C[C@@H]4CCN3C[C@@H]4C=C)O
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C20H24N2O2
Computed by PubChem 2.2 (PubChem release 2024.11.20)

2.3 Other Identifiers

2.3.1 CAS

56-54-2
50-54-4

2.3.2 Deprecated CAS

11010-73-4, 1528764-92-2, 2393956-08-4, 500225-45-6, 845886-64-8, 882741-47-1, 883881-01-4, 898814-00-1, 910899-51-3
11010-73-4, 1528764-92-2, 500225-45-6, 845886-64-8, 882741-47-1, 883881-01-4, 910899-51-3

2.3.3 European Community (EC) Number

2.3.4 UNII

2.3.5 UN Number

2.3.6 ChEBI ID

2.3.7 ChEMBL ID

2.3.8 DrugBank ID

2.3.9 DSSTox Substance ID

2.3.10 HMDB ID

2.3.11 KEGG ID

2.3.12 Metabolomics Workbench ID

2.3.13 NCI Thesaurus Code

2.3.14 PharmGKB ID

2.3.15 Pharos Ligand ID

2.3.16 RXCUI

2.3.17 Wikidata

2.3.18 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • Adaquin
  • Apo Quinidine
  • Apo-Quinidine
  • Chinidin
  • Quincardine
  • Quinidex
  • Quinidine
  • Quinidine Sulfate
  • Quinora
  • Sulfate, Quinidine

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
324.4 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
XLogP3
Property Value
2.9
Reference
Computed by XLogP3 3.0 (PubChem release 2024.11.20)
Property Name
Hydrogen Bond Donor Count
Property Value
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Hydrogen Bond Acceptor Count
Property Value
4
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Rotatable Bond Count
Property Value
4
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Exact Mass
Property Value
324.183778013 Da
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
Monoisotopic Mass
Property Value
324.183778013 Da
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
Topological Polar Surface Area
Property Value
45.6 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Heavy Atom Count
Property Value
24
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
457
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
4
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Physical Description

Crystals or white powder. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
Triboluminescent solid; [Merck Index]
Solid

3.2.2 Color / Form

CRYSTALS WITH 2.5 MOL WATER OF CRYSTALLIZATION; CRYSTALS FROM DILUTE ALCOHOL
Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 73rd ed. Boca Raton, FL: CRC Press Inc., 1992-1993., p. 3-440
Occurs as fine, needle-like, white crystals which frequently cohere in masses or as a fine, white powder.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 992

3.2.3 Taste

Very bitter taste
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 992

3.2.4 Melting Point

331 to 336 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
174 °C
PhysProp
174-175 °C after drying of solvated crystals
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1443
Prisms from dilute alcohol; loses one-half water in air; MP: about 168 °C /Hemipentahydrate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1443
Crystals from water; mp: 248 °C (dry); readily soluble in hot water, alcohol. /Quinidine methiodide monohydrate/
Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 1283
174 °C

3.2.5 Solubility

>48.7 [ug/mL] (The mean of the results at pH 7.4)
less than 0.1 mg/mL at 64 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
140 mg/L (at 25 °C)
YALKOWSKY,SH & DANNENFELSER,RM (1992)
Lustrous needles; decomposes at 259 °C (drug); specific optical rotation at 20 °C/D + 200 deg ; sol in 60 parts water, freely soluble in hot water, in alcohol, chloroform, slightly in ether; neutral reaction. /Quinidine hydrochloride monohydrate/
Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 1282
1 g /quinidine/ dissolves in about 36 ml alcohol, 56 ml ether, 1.6 ml chloroform; very soluble in methanol; practically insoluble in petroleum ether.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1443
Soluble in benzene
Lide, DR (ed.). CRC Handbook of Chemistry and Physics. 81st Edition. CRC Press LLC, Boca Raton: FL 2000, p. 3-114
In water, 140 mg/l @ 25 °C
Yalkowsky SH, Dannenfelser RM; The AQUASOL dATAbASE of Aqueous Solubility. Ver 5. Tucson, AZ: Univ AZ, College of Pharmacy (1992)
WHITE; VERY BITTER; ODORLESS; FINE CRYSTALS; FREQUENTLY COHERING IN MASSES; PH (1% AQUEOUS SOLN): 6.0-6.8 PKA: 4.2, 8.8; SPECIFIC OPTICAL ROTATION: +212 @ 25 °C/D (95% ALCOHOL); ABOUT + 260 @ 25 °C/D (DILUTE HYDROCHLORIC ACID); DOES NOT LOSE ALL OF ITS WATER BELOW 120 °C 1 G DISSOLVES IN ABOUT 90 ML WATER, 15 ML BOILING WATER, 10 ML ALCOHOL, 3 ML METHANOL, 12 ML CHLOROFORM; INSOL IN ETHER, BENZENE; /DIHYDRATE/
Slightly sol in water and soluble in alcohol.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 992
3.34e-01 g/L

3.2.6 LogP

3.44
HANSCH,C ET AL. (1995)
log Kow = 2.88
Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 168
2.6

3.2.7 LogS

-3.37
ADME Research, USCD

3.2.8 Stability / Shelf Life

Quinidine gluconate, quinidine polygalacturonate, and quinidine sulfate darken on exposure to light and should be stored in well-closed, light resistant containers. Solutions of quinidine salts slowly acquire a brownish tint on exposure to light. Only colorless, clear solutions of quinidine gluconate injection should be used. Quinidine gluconate injection should be stored at 15-30 °C. When diluted to a concentration of 16 mg/ml with 5% dextrose injection, quinidine gluconate injection is stable for 24 hours at room temperature and up to 48 hours when refrigerated. /Quinidine salts/
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1571
PROTECT FROM LIGHT; DARKENS ON EXPOSURE TO LIGHT /DIHYDRATE/
Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 1283
Quinidine gluconate, quinidine polygalacturonate, and quinidine sulfate darken on exposure to light and should be stored in well closed, light-resistant containers. Solutions of quinidine salts slowly acquire a brownish tint on exposure to light. Only colorless, clear solutions of quinidine gluconate injection should be used. Quinidine gluconate injection should be stored at 15-30 °C. When diluted to a concentration of 16 mg/ml with 5% dextrose injection, quinidine gluconate injection is stable for 24 hr at room temperature and up to 48 hr when refrigerated. /Quindine salts/
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 992

3.2.9 Optical Rotation

Specific optical rotation @ 15 °C/D + 230 deg (concn by volume = 1.8 in chloroform); specific optical rotation @ 17 °C/D + 258 deg (alcohol); +322 deg (concn by volume = 1.6 in 2 M HCl); UV absorption spectrum is identical with that of quinine; blue fluorescence in dilute H2SO4.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1443
MAX ABSORPTION (METHANOL): 230 NM (LOG E= 4.53); 280 NM (LOG E= 3.54); 336 NM (LOG E= 3.69); SPECIFIC OPTICAL ROTATION (ALCOHOL) @ 25 °C/D +212 DEG
Weast, R.C. (ed.). Handbook of Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc., 1979., p. C-480
Specific optical rotation: + 212 deg at 25 °C/D (alcohol); prisms; needles from water. /d-quinidine sulfate/
Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 73rd ed. Boca Raton, FL: CRC Press Inc., 1992-1993., p. 3-440

3.2.10 Decomposition

When heated to decomposition it emits toxic fumes of oxides of nitrogen.
Sax, N.I. Dangerous Properties of Industrial Materials. 6th ed. New York, NY: Van Nostrand Reinhold, 1984., p. 2348
When heated to decomposition it emits very toxic fumes of /nitrogen oxides and sulfur oxides/.
Sax, N.I. Dangerous Properties of Industrial Materials. 6th ed. New York, NY: Van Nostrand Reinhold, 1984., p. 2348

3.2.11 Refractive Index

INDEX OF REFRACTION ALPHA 1.565; BETA 1.607; GAMMA 1.670. OPTIC SIGN +, EXTINCTION PARALLEL, ELONGATION +
Association of Official Analytical Chemists. Official Methods of Analysis. 10th ed. and supplements. Washington, DC: Association of Official Analytical Chemists, 1965. New editions through 13th ed. plus supplements, 1982., p. 12/1029

3.2.12 Caco2 Permeability

-4.69
ADME Research, USCD

3.2.13 Dissociation Constants

Basic pKa
8.05
Comparison of the accuracy of experimental and predicted pKa values of basic and acidic compounds. Pharm Res. 2014; 31(4):1082-95. DOI:10.1007/s11095-013-1232-z. PMID:24249037
pKa
8.56 (at 25 °C)
SANGSTER (1994)
pK1 @ 20 °C = 5.4; pK2 = 10.0
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1443
pKa = 8.56 @ 25 °C
Sangster J; LOGKOW Databank. Sangster Res. Lab., Montreal Quebec, Canada (1994)

3.2.14 Collision Cross Section

175.8 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

3.2.15 Other Experimental Properties

Rods; soluble in 8 parts water with blue fluorescence /Acid sulfate tetrahydrate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1443
Crystals from water; decomposes at 115 °C; specific optical rotation at 15 °C/D + 223 deg (0.4 molar solution). /Quinidine dihydrobromide trihydrate/
Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 1282
Crystals; MP: 175-176.5 °C; sol in 9 parts water, 60 parts alcohol /Gluconate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1443
ODORLESS; VERY BITTER TASTE; SOLN ARE NEUTRAL OR ALKALINE TO LITMUS
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 795
Rods; soluble in 8 parts water with blue fluorescence. /Quinidine acid sulfate tetrahydrate/
Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 1282

3.3 SpringerMaterials Properties

3.4 Chemical Classes

Biological Agents -> Plant Toxins

3.4.1 Drugs

Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
3.4.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Antiarrhythmics
Human drug -> Discontinued
Human drug -> Prescription; Discontinued; Active ingredient (QUINIDINE SULFATE)
Pharmaceuticals
S72 | NTUPHTW | Pharmaceutically Active Substances from National Taiwan University | DOI:10.5281/zenodo.3955664

4 Spectral Information

4.1 1D NMR Spectra

4.1.1 13C NMR Spectra

1 of 2
Source of Sample
E. Merck AG, Darmstadt, Germany
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Copyright
Copyright © 2016-2024 W. Robien, Inst. of Org. Chem., Univ. of Vienna. All Rights Reserved.
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4.2 Mass Spectrometry

4.2.1 GC-MS

1 of 2
Source of Spectrum
Mass Spectrometry Committee of the Toxicology Section of the American Academy of Forensic Sciences
Copyright
Copyright © 2012-2024 John Wiley & Sons, Inc. Portions provided by AAFS, Toxicology Section. All Rights Reserved.
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2 of 2
Source of Spectrum
Mass Spectrometry Committee of the Toxicology Section of the American Academy of Forensic Sciences
Copyright
Copyright © 2012-2024 John Wiley & Sons, Inc. Portions provided by AAFS, Toxicology Section. All Rights Reserved.
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4.2.2 MS-MS

1 of 6
View All
Spectra ID
Instrument Type
LC-ESI-qTof
Ionization Mode
Positive
Top 5 Peaks

117.056435 32136

160.074936 31228

146.059097 20872

174.054581 16876

145.051208 14104

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Notes
From GNPS Library
2 of 6
View All
Spectra ID
Instrument Type
LC-ESI-qTof
Ionization Mode
Positive
Top 5 Peaks

325.188812 10320

172.073563 5164

160.074005 4960

307.179169 4804

184.074554 2572

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Notes
From GNPS Library

4.2.3 LC-MS

1 of 8
View All
Authors
Markus Kohlhoff, Natural Product Chemistry Lab (FIOCRUZ Minas, Brazil)
Instrument
maXis (Bruker Daltonics)
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
10 eV
Fragmentation Mode
CID
Column Name
Shimadzu Shim-Pack XR-ODS III; C18; 2.2um; 80A; 2.0x150mm
Precursor Adduct
[M+H]+
Top 5 Peaks

325.1911 999

326.1942 199

327.197 23

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License
CC BY
2 of 8
View All
Authors
Markus Kohlhoff, Natural Product Chemistry Lab (FIOCRUZ Minas, Brazil)
Instrument
maXis (Bruker Daltonics)
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
20 eV
Fragmentation Mode
CID
Column Name
Shimadzu Shim-Pack XR-ODS III; C18; 2.2um; 80A; 2.0x150mm
Precursor Adduct
[M+H]+
Top 5 Peaks

325.1916 999

326.1947 196

307.1808 39

327.1976 23

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License
CC BY

4.2.4 Other MS

1 of 4
View All
Other MS
MASS: 1940 (Atlas of Mass Spectral Data, John Wiley & Sons, New York) /Quinidine hydrate/
Other MS
MASS: 35750 (NIST/EPA/MSDS Mass Spectral Database, 1990 version)
2 of 4
View All
MS Category
Experimental
MS Type
Other
MS Level
MS2
Precursor Type
[M+H]+
Precursor m/z
325.1912273652373
Ionization Mode
positive
Retention Time
2.01
Top 5 Peaks

325.19519818339353 100

160.0753603589196 33.18

307.1827504925839 22.52

81.06962240397715 17.11

172.07460727803436 16.12

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4.3 UV Spectra

UV: 4-824 (Organic Electronic Spectral Data, Phillips et al, John Wiley and Sons, NY)
Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V3 2107
UV: 11429 (Sadtler Research Laboratories Spectral Collection)
Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and II. Boca Raton, FL: CRC Press Inc. 1985., p. V2 239

4.4 IR Spectra

1 of 2
IR Spectra
IR: 9516 (Sadtler Research Laboratories Prism Collection) /Quinidine hydrate/
2 of 2
IR Spectra
IR: 8162 (Sadtler Research Laboratories IR Grating Collection)

4.4.1 ATR-IR Spectra

Instrument Name
Bio-Rad FTS
Technique
ATR-Neat (DuraSamplIR II)
Source of Spectrum
Forensic Spectral Research
Source of Sample
Sigma-Aldrich Inc.
Catalog Number
Q3625
Lot Number
1343473
Copyright
Copyright © 2009-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.5 Raman Spectra

1 of 2
Technique
FT-Raman
Source of Spectrum
Forensic Spectral Research
Source of Sample
Sigma-Aldrich Inc.
Catalog Number
Q3625
Lot Number
1343473
Copyright
Copyright © 2012-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Catalog Number
145882
Copyright
Copyright © 2017-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2017-2024 John Wiley & Sons, Inc. All Rights Reserved.
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6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

Quinidine is indicated for the management and prophylactic therapy of atrial fibrillation/flutter, as well as the suppression of recurrent documented ventricular arrhythmias. It is also used in the treatment of Brugada syndrome, short QT syndrome and idiopathic ventricular fibrillation..

7.2 LiverTox Summary

Quinidine is a natural cinchona alkaloid which has potent antiarrhythmic activity and has been used for decades in the treatment of atrial and ventricular arrhythmias. Quinidine has been associated with fever, mild jaundice and clinically apparent liver injury in up to 2% of treated patients.

7.3 Drug Classes

Breast Feeding; Lactation; Milk, Human; Antiarrhythmics
Antiarrhythmic Agents

7.4 FDA Approved Drugs

7.5 FDA Orange Book

7.6 FDA National Drug Code Directory

7.7 Drug Labels

Drug and label
Active ingredient and drug

7.8 Clinical Trials

7.8.1 ClinicalTrials.gov

7.8.2 EU Clinical Trials Register

7.8.3 NIPH Clinical Trials Search of Japan

7.9 Therapeutic Uses

Adrenergic alpha-Antagonists; Anti-Arrhythmia Agents; Antimalarials; Enzyme Inhibitors; Muscarinic Antagonists
National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)
Quinidine is indicated in the treatment of recurrent, documented, life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia. Quinidine should not be used to treat ventricular arrhythmias of lesser severity, such as asymptomatic ventricular premature contractions. /Included in US product labeling/
MICROMEDEX Thomson Health Care. USPDI - Drug Information for the Health Care Professional. 22nd ed. Volume 1. MICROMEDEX Thomson Health Care, Greenwood Village, CO. 2002. Content Reviewed and Approved by the U.S. Pharmacopeial Convention, Inc., p. 2482
Quinidine is indicated in the treatment of symptomatic atrial fibrillation or flutter in patients whose symptoms are not controlled by measures to reduce the rate of ventricular response. /US Product Labeling/
MICROMEDEX Thomson Health Care. USPDI - Drug Information for the Health Care Professional. 22nd ed. Volume 1. MICROMEDEX Thomson Health Care, Greenwood Village, CO. 2002. Content Reviewed and Approved by the U.S. Pharmacopeial Convention, Inc., p. 2483
Chronic quinidine treatment is indicated for some patients at high risk for symptomatic atrial fibrillation pr flutter, such as those who have had previous episodes taht are so frequent and poorly tolerated as to outweigh the risk of porphylactic therapy with quinidine. /US Product Labeling/
MICROMEDEX Thomson Health Care. USPDI - Drug Information for the Health Care Professional. 22nd ed. Volume 1. MICROMEDEX Thomson Health Care, Greenwood Village, CO. 2002. Content Reviewed and Approved by the U.S. Pharmacopeial Convention, Inc., p. 2483
Intravenous quinidine is indicated in the treatment of life-threatening Plasmodium falciparum malaria. /US Product Labeling/
MICROMEDEX Thomson Health Care. USPDI - Drug Information for the Health Care Professional. 22nd ed. Volume 1. MICROMEDEX Thomson Health Care, Greenwood Village, CO. 2002. Content Reviewed and Approved by the U.S. Pharmacopeial Convention, Inc., p. 2483
MEDICATION (VET): OF 6 ANTIARRHYTHMICS TESTED, QUINIDINE BISULFATE GAVE NO PROTECTION AGAINST THE INDUCED ARRHYTHMIA IN DOGS.
FERNANDEZ MZ ET AL; REV COLOMB CIENC QUIM-FARM 3 (3): 65 (1979)
... IS EFFECTIVE FOR SHORT- AND LONG-TERM TREATMENT OF SUPRAVENTRICULAR AND VENTRICULAR ARRHYTHMIAS. /QUINIDINE/
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 854
FOR PRACTICAL PURPOSES, QUINIDINE IS ONLY GIVEN ORALLY, ALTHOUGH IT CAN BE ADMINEITHER IM OR IV UNDER SPECIAL CIRCUMSTANCES. THE USUAL ORAL DOSE OF QUINIDINE SULFATE IS 200 TO 300 MG THREE TO FOUR TIMES A DAY. ... FOR PATIENTS WITH PREMATURE ATRIAL OR VENTRICULAR CONTRACTIONS OR MAINTENANCE THERAPY. HIGHER AND/OR MORE FREQUENT DOSES CAN BE USED FOR LIMITED PERIODS FOR TREATMENT OF PAROXYSMAL VENTRICULAR TACHYCARDIA.
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 853
Quinidine is used primarily as prophylactic therapy to maintain normal sinus rhythm after conversion of atrial fibrillation and/or flutter by other methods. The drug is also used to prevent the recurrence of paroxysmal atrial fibrillation, paroxysmal atrial tachycardia, paroxysmal atrioventricular junctional rhythm, paroxysmal ventricular tachycardia, and atrial or ventricular premature contractions.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 993
For more Therapeutic Uses (Complete) data for QUINIDINE SULFATE (7 total), please visit the HSDB record page.

7.10 Drug Warnings

Skin reactions to quinidine are rare and include morbilliform and scarlatiniformeruptions, urticaria, rash, pruritus, exfoliative dermatitis, eczema, severe exacerbation of psoriasis, lichenoid reactions, flushing, pigmentary abnormalities, photodermatitis (photosensitivity), and contact dermatitis.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1566
... Adverse reactions are not related to plasma concentration and include drug fever cholestatic hepatitis, systemic lupus erythematosus, asthma, anaphylaxis, thrombocytopenia, hemolytic anemia (especially in glutcose-6-phosphate dehydrogenase deficiency), and hypoprothrombinemia. Skin changes range from maculopapular eruption to thrombocytopenic purpura, cutaneous vasculitis, photosensitivity, and bullous lesions.
Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 511
Drug induced agranulocytosisis a clinical entity characterized by a selective reduction of circulating neutrophils, usually to a level less than 0.2X10+9/l in relation to the administration of the drug. Quinidine is an antiarrhythmic agent widely used on an outpatient basis with some well known hematological side effects. Its midterm administration has been related to a few cases of agranulocytosis. The case of a 60 yr old man with atrial fibrillation is described who presented quinidine induced agranulocytosis of abrupt onset only 3 days after the exposure to the drug, recovering normal levels of neutrophils during the third hospitalization day.
Sureda A et al; Acta Haematol 84 (1): 43-4 (1990)
Large doses ...increase temporal dispersion of ventricular refractory periods ...may induce idioventricular impulse generation. Caution ...mandatory in ...treatment of ventricular ectopic rhythms; increased dose after therapeutic failure may increase hazard.
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 689
For more Drug Warnings (Complete) data for QUINIDINE (34 total), please visit the HSDB record page.
OCCASIONALLY PATIENTS TAKING QUINIDINE EXPERIENCE SYNCOPE OR SUDDEN DEATH. ... MAY BE RESULT OF HIGH CONCENTRATIONS OF QUINIDINE IN PLASMA OR RESULT OF COEXISTING DIGITALIS TOXICITY. /QUINIDINE/
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 853
INDIVIDUALS WITH THE LONG Q-T SYNDROME OR THOSE WHO RESPOND TO LOW CONCENTRATIONS OF QUINIDINE WITH MARKED LENGTHENING OF THE Q-T INTERVAL APPEAR TO BE PARTICULARLY AT RISK /OF SYNCOPE OR SUDDEN DEATH/ AND SHOULD NOT BE TREATED WITH THIS DRUG. /QUINIDINE/
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 853
EXCESSIVE CONCENTRATION OF DRUG IN PLASMA WILL CAUSE ADVERSE EFFECTS IN ANY PATIENT. BECAUSE QUINIDINE HAS LOW THERAPEUTIC RATIO, CONSTANT VIGILANCE IS THUS REQUIRED IN EVERY PATIENT TAKING THIS DRUG. /QUINIDINE/
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 853
Quinidine should be used with extreme caution, if at all, in patients with incomplete atrioventricular nodal block, since complete heart block and asystole may result. Im or iv administration of quinidine is especially hazardous in the presence of atrioventricular block, in the absence of atrial activity, and the patients with extensive myocardial injury. Hypokalemia, hypoxia, and disorders of acid base balance must be eliminated as potentiating factors in patients who require large doses of antiarrhythmic agents to control ventricular arrhythmias.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 995
For more Drug Warnings (Complete) data for QUINIDINE SULFATE (24 total), please visit the HSDB record page.

7.11 Drug Idiosyncrasies

Skin reactions to quinidine are rare and include morbilliform and scarlatiniform eruptions, urticaria, rash, pruritus, exfoliative dermatitis, eczema, severe exacerbation of psoriasis, lichenoid reactions, flushing, pigmentary abnormalities, photodermatitis (photosensitivity), and contact dermatitis. /Quinidine/
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 994
Quinidine has produced a systemic lupus erythematosus-like syndrome charaterized by polyarthritis, fever, pleuritic chest pain, lupus nephritis, and the presence of antinuclear antibodies in the blood. /Quinidine/
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 994

8 Pharmacology and Biochemistry

8.1 Pharmacodynamics

Quinidine is an antimalarial schizonticide, and a class Ia antiarrhythmic agent used to interrupt or prevent reentrant arrhythmias and arrhythmias due to increased automaticity, such as atrial flutter, atrial fibrillation, and paroxysmal supraventricular tachycardia. In most patients, quinidine can lead to an increase in the sinus rate. Quinidine also causes a marked prolongation of the QT interval in a dose-related manner, acts peripherally as an α-adrenergic antagonist, and has anticholinergic and negative inotropic activity. The QT interval prolongation caused by quinidine can lead to increased ventricular automaticity and polymorphic ventricular tachycardias, such as _torsades de pointes_. The risk of _torsades_ is increased by bradycardia, hypokalemia, hypomagnesemia or high serum levels of quinidine. However, this type of rhythm disturbance may appear in the absence of any of them. Patients treated with quinidine may also be at risk of a paradoxical increase in ventricular rate in atrial flutter/fibrillation, and patients with sick sinus syndrome treated with quinidine may develop marked sinus node depression and bradycardia.

8.2 MeSH Pharmacological Classification

Adrenergic alpha-Antagonists
Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma. (See all compounds classified as Adrenergic alpha-Antagonists.)
Muscarinic Antagonists
Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system. (See all compounds classified as Muscarinic Antagonists.)
Anti-Arrhythmia Agents
Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade. (See all compounds classified as Anti-Arrhythmia Agents.)
Cytochrome P-450 CYP2D6 Inhibitors
Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP2D6. (See all compounds classified as Cytochrome P-450 CYP2D6 Inhibitors.)
Antimalarials
Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585) (See all compounds classified as Antimalarials.)
Enzyme Inhibitors
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. (See all compounds classified as Enzyme Inhibitors.)
Voltage-Gated Sodium Channel Blockers
A class of drugs that inhibit the activation of VOLTAGE-GATED SODIUM CHANNELS. (See all compounds classified as Voltage-Gated Sodium Channel Blockers.)

8.3 FDA Pharmacological Classification

1 of 2
FDA UNII
ITX08688JL
Active Moiety
QUINIDINE
Pharmacological Classes
Established Pharmacologic Class [EPC] - Antiarrhythmic
Pharmacological Classes
Established Pharmacologic Class [EPC] - Cytochrome P450 2D6 Inhibitor
Pharmacological Classes
Mechanisms of Action [MoA] - Cytochrome P450 2D6 Inhibitors
FDA Pharmacology Summary
Quinidine is an Antiarrhythmic and Cytochrome P450 2D6 Inhibitor. The mechanism of action of quinidine is as a Cytochrome P450 2D6 Inhibitor.
2 of 2
Non-Proprietary Name
QUINIDINE SULFATE
Pharmacological Classes
Cytochrome P450 2D6 Inhibitors [MoA]; Antiarrhythmic [EPC]; Cytochrome P450 2D6 Inhibitor [EPC]

8.4 ATC Code

C - Cardiovascular system

C01 - Cardiac therapy

C01B - Antiarrhythmics, class i and iii

C01BA - Antiarrhythmics, class ia

C01BA01 - Quinidine

8.5 Absorption, Distribution and Excretion

Absorption
The absolute bioavailability of quinidine sulfate is approximately 70%, but it ranges from 45% to 100%. The less-than-complete quinidine sulfate bioavailability is a result of first-pass metabolism in the liver. In contrast, the absolute bioavailability of quinidine gluconate ranges from 70% to 80%, and relative to quinidine sulfate, quinidine from quinidine gluconate has a bioavailability of 1.03. The tmax of quinidine sulfate extended-release tablets is approximately 6 h, while the tmax of quinidine gluconate goes from 3 to 5 h. The peak serum concentration reached with immediate-release quinidine sulfate is delayed for about an hour when taken with food. Furthermore, the ingestion of grapefruit juice may decrease the rate of absorption of quinidine.
Route of Elimination
The elimination of quinidine is achieved by the renal excretion of the unchanged drug (15 to 40% of total clearance) and its hepatic biotransformation to a variety of metabolites (60 to 85% of total clearance). When urine has a pH lower than 7, 20% of administered quinidine appears in urine unchanged. However, this proportion decreases to as little as 5% as it becomes more alkaline. The renal clearance of quinidine involves both glomerular filtration and active tubular secretion, moderated by pH-dependent tubular reabsorption.
Volume of Distribution
Quinidine has a volume of distribution of 2-3 L/kg in healthy young adults, 0.5 L/kg in patients with congestive heart failure, and 3-5 L/kg in patients with liver cirrhosis.
Clearance
The clearance of quinidine ranges from 3 to 5 mL/min/kg in adults. In pediatric patients, quinidine clearance may be two or three times as rapid.
The volume of distribution of quinidine is 2 to 3 L/kg in healthy young adults, but this may be reduced to as little as 0.5 L/kg in patients with congestive heart failure, or increased to 3 or 5 L/kg in patients with cirrhosis of the liver. At concentrations of 2 to 5 mg/L (6.5 to 16.2 umol/L), the fraction of quinidine bound to plasma proteins (mainly to (alpha)1-acid glycoprotein and to albumin) is 80 to 88% in adults and older children, but it is lower in pregnant women, and in infants and neonates it may be as low as 50 to 70%. Because (alpha)1-glycoprotein levels are increased in response to stress, serum levels of total quinidine may be greatly increased in settings such as acute myocardial infarction, even though the serum content of unbound (active) drug may remain normal. Protein binding is also increased in chronic renal failure, but binding abruptly descends toward or below normal when heparin is administered for hemodialysis.
Medical Economics Co; Physicians Desk Reference 56th ed p. 2933 (2002)
...Essentially completely absorbed after oral admin; max effects occur within 1-3 hr, and persist for 6-8 more hr. Large fluctuations in plasma concentration... if repeated doses are given at this interval. ...IM admin... gluconate yields peak effects in 30-90 min.
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 291
...All administered compound is excreted by kidney, and about 10-50% appears in urine as unchanged quinidine, within 24 hr.
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 692
The bioavailability of quinidine is 70 to 80% after oral use but varies between individuals and preparations. The sulfate salt is rapidly absorbed in 60 to 90 minutes. Polygalacturonate salts produce peak quinidine concentrations in 5 to 6 hours; gastrointestinal absorption of gluconate salts is intermediate (peak 3-4 hours).
Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 510
For more Absorption, Distribution and Excretion (Complete) data for QUINIDINE (14 total), please visit the HSDB record page.
ABOUT 90% OF QUINIDINE IN PLASMA IS BOUND TO PLASMA PROTEINS (ALPHA/ACID GLYCOPROTEIN AND ALBUMIN) THE DRUG ENTERS ERYTHROCYTES & ... BINDS TO HEMOGLOBIN; AT STEADY STATE, CONCN OF QUINIDINE IN PLASMA & ERYTHROCYTES ARE APPROXIMATELY EQUAL. QUINIDINE ACCUMULATES RAPIDLY IN MOST TISSUES EXCEPT BRAIN, & ... VOL OF DISTRIBUTION IS 2-3 L/KG. /QUINIDINE/
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 852
METABOLITES AND SOME OF THE PARENT DRUG (20%) ARE EXCRETED IN URINE; ELIMINATION HALF-TIME IS ABOUT 6 HR. /QUINIDINE/
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 852
LIVER METABOLISM & RENAL EXCRETION ARE THE MAIN ROUTES OF ELIMINATION. ENTEROHEPATIC CIRCULATION WOULD NOT SIGNIFICANTLY ALTER ABSORPTION KINETICS AS REFLECTED BY BLOOD CONCENTRATION.
KOSKAS J ET AL; J PHARM BELG 36 (3): 193 (1981)
PEAK PLASMA CONCN OF 0.29 UG/ML OF QUINIDINE WERE MEASURED @ 4 HR AFTER ADMIN OF SUSTAINED RELEASE CAPSULE (250 MG QUINIDINE BISULFATE) AND DECLINED STEADILY DURING THE NEXT 8 HR, WHILE AFTER ADMIN OF SUSTAINED RELEASE TABLET (300 MG QUINIDINE SULFATE) THEY WERE FAIRLY EVEN DURING 2-10 HR AFTER DOSING. PLASMA CONCENTRATIONS WERE HIGHER AT LATER TIMES FOR THE CAPSULE THAN FOR THE TABLET. THE BIOAVAILABILITY OF QUINIDINE FROM THE CAPSULES DURING 12 HR WAS 184% COMPARED TO THE TABLET. MEAN QUINIDINE PLASMA CONCN WERE SIGNIFICANTLY GREATER @ 3, 4, 6, 8, & 10 HR AFTER ADMIN OF THE CAPSULE THAN AFTER THE TABLET.
CHASSEAUD LF ET AL; PHARM IND 38 (5): 488 (1976)
For more Absorption, Distribution and Excretion (Complete) data for QUINIDINE SULFATE (24 total), please visit the HSDB record page.

8.6 Metabolism / Metabolites

Quinidine is mainly metabolized in the liver by cytochrome P450 enzymes, specifically CYP3A4. The major metabolite of quinidine is 3-hydroxy-quinidine, which has a volume of distribution larger than quinidine and an elimination half-life of about 12 hours. Non-clinical and clinical studies suggest that 3-hydroxy-quinidine has approximately half the antiarrhythmic activity of quinidine; therefore, this metabolite is partly responsible for the effects detected with the chronic use of quinidine.
Lactate conjugates of quinidine and its 3-hydroxy metabolite were detected in overdose suicide patient.
Leferink et al; J Anal Toxicol 1 (2): 62-5 (1977)
Quinidine is metabolized in the liver, principally via hydroxylation to 3-hydroxyquinidine and 2-quinidinone. Some metabolites have antiarrhythmic activity. Approximately 10-50% of a dose is excreted in urine (probably by glomerular filtration) as unchanged drug within 24 hr.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1571
Quinidine metabolites include 3-hydroxyquinidine N-oxide, 2'-oxoquinidinone, desmethylquinidine, and quinidine N-oxide. While metabolism is highly variable between individuals, at least in cases of quinidine-induced torsade de pointes, the metabolites do not appear to contribute to the formation of dysrhythmias.
Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 510
Quinidine undergoes extensive hepatic oxidative metabolism... One metabolite, 3-hydroxyquinidine, is nearly as potent as quinidine in blocking cardiac sodium channels or prolonging action potentials.
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 966
Most quindiidne is eliminated hepatically via the action of cytochrome P450 IIIA.
Medical Economics Co; Physicians Desk Reference 56th ed p. 2933 (2002)
QUINIDINE YIELDS 2'-HYDROXYQUINIDINE AS METABOLITE IN MAN. /QUINIDINE; FROM TABLE/
Goodwin, B.L. Handbook of Intermediary Metabolism of Aromatic Compounds. New York: Wiley, 1976., p. Q-3
MOST URINARY METABOLITES ARE HYDROXYLATED AT ONLY ONE SITE, EITHER ON THE QUINOLINE RING OR ON THE QUINUCLIDINE RING; SMALL AMOUNTS OF DIHYDROXY COMPOUNDS ARE ALSO FOUND. THE FRACTION OF A DOSE OF QUINIDINE THAT IS METABOLIZED & THE METABOLIC PATHWAY APPEAR TO VARY CONSIDERABLY FROM PATIENT TO PATIENT.
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 852
Quinidine is metabolized in the liver, principally via hydroxylation to 3-hydroxyquinidine and 2-quinidinone. The metabolites may be pharmacologically active. Approximately 10-50% of a dose is excreted in urine (probably by glomerular filtration) as unchanged drug within 24 hr. /Quinidine/
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 993
Quinidine has known human metabolites that include 3-Hydroxyquinidine and Quinidine-N-oxide.
S73 | METXBIODB | Metabolite Reaction Database from BioTransformer | DOI:10.5281/zenodo.4056560

8.7 Biological Half-Life

The elimination half-life of quinidine is 6-8 hours in adults and 3-4 hours in pediatric patients.
Quinidine generally has a plasma half-life of 6-8 hr in healthy inividuals, but half-life may range from 3-16 hr or longer. In one study in patients with Plasmodium falciparum malaria, the elimination half-life of the drug averaged 12.8 hr (range: 6.6-24.8 hr).
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1571
The usual plasma half-life of approximately 7 hours after intravenous administration is increased in the presence of chronic liver disease.
Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 510
THE ELIMINATION HALF-LIFE OF QUINIDINE RANGES FROM 4 TO 10 HR IN HEALTHY PERSONS, WITH USUAL MEAN VALUE OF 6 TO 7 HR. HALF-LIFE IS SIGNIFICANTLY PROLONGED IN ELDERLY PERSONS, EVEN WHEN THEY ARE APPARENTLY HEALTHY. /QUINIDINE/
Miller, R. R., and D. J. Greenblatt. Handbook of Drug Therapy. New York: Elsevier North Holland, 1979., p. 299
... EXCRETED IN URINE; ELIMINATION HALF-TIME IS ABOUT 6 HR. /QUINIDINE/
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 852
Quinidine generally has a plasma half-life of 6-8 hr in healthy individuals, but half-life may range from 3-16 hr or longer. In one study in patients with Plasmodium falciparum malaria, the elimination half-life of the drug averaged 12.8 hr (range: 6.6-24.8 hr). /Quinidine/
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 993

8.8 Mechanism of Action

Quinidine has a complex electrophysiological profile that has not been fully elucidated. The antiarrhythmic actions of this drug are mediated through effects on sodium channels in Purkinje fibers. Quinidine blocks the rapid sodium channel (INa), decreasing the phase zero of rapid depolarization of the action potential. Quinidine also reduces repolarizing K+ currents (IKr, IKs), the inward rectifier potassium current (IK1), and the transient outward potassium current Ito, as well as the L-type calcium current ICa and the late INa inward current. The reduction of these currents leads to the prolongation of the action potential duration. By shortening the plateau but prolonging late depolarization, quinidine facilitates the formation of early afterdepolarisation (EAD). Additionally, in patients with malaria, quinidine acts primarily as an intra-erythrocytic schizonticide, and is gametocidal to _Plasmodium vivax_ and _P. malariae_, but not to _P. falciparum_.
The exact mechanism of antiarrhythmic action of quinidine has not been determined conclusively, but the drug is considered a class I (membrane stabilizing) antiarrhythmic agent. Like other class I antiarrhythmic agents, quinidine is believed to combine with fast sodium channels in their inactive state and thereby inhibit recovery after repolarization in a time- and voltage-dependent manner, which is associated with subsequent dissociation of the drug from the sodium channels. Quinidine exhibits electrophysiologic effects characteristic of class IA antiarrhythmic agents. The electrophysiologic characteristics of the subgroups of class I antiarrhythmic agents may be related to quantitative differences in their rates of attachment to and dissociation from transmembrane sodium channels, with class IA agents exhibiting intermediate rates of attachment and dissociation.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1570
Like lidocaine and procainamide, quinidine suppresses automaticity in the His-Purkinje system. In usual doses, quinidine may decrease the automaticity of ectopic pacemakers, but the extent of this effect also depends upon the anticholinergic effect of the drug on the sinoatrial node, atria, and atrioventricular node. Extremely high concentrations of quinidine may increase myocardial automaticity. The drug decreases conduction velocity in the atria, ventricles, and His-Purkinje system, and may decrease or cause no change in conduction velocity through the AV node. Quinidine probably suppresses atrial fibrillation or flutter by prolonging the effective refractory period and increasing the action potential duration in atrial and ventricular muscle and in the His-Purkinje system. Because prolongation of the effective refractory period is greater than the increase in the duration of the action potential, the cardiac tissue remains refractory even after restoration of the resting membrane potential. Quinidine shortens the effective refractory period of the atrioventricular node, and the anticholinergic action of the drug may also increase the conductivity of the atrioventricular node. The effects of quinidine on refractoriness and the action potential duration of atrial fibers may be modified by the anticholinergic effects of the drug. Quinidine decreases cardiac excitability, both in diastole and in the relative refractory period, by increasing the threshold potential for electrical excitation. At therapeutic plasma concentrations, quinidine causes prolongation of the QRS complex and QT interval.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1570
Quinidine also exhibits some antipyretic and oxytocic properties. Quinidine has a very weak curare-like action on the myoneural junction and also causes depression of skeletal muscle action potential.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1570
Intravenous quinidine depresses contractility and decreases systemic vascular resistance primarily by alpha-adrenergic receptor blockade. High blood levels of quinidine increase left ventricular end-diastolic pressure through its negative inotropic effect. Cardiovascular collapse has resulted from depression of contractility.
Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 511
Quindine primarily kills the schizont parasite at the asexual intra-erythrocytic cycle stage of the Plasmodium falciparum malaria protozoan parasite. Quinidine also kills the gametocyte parasite stages of Plasmodium malariae, Plasmodium vivax, and Plasmodium ovale.
MICROMEDEX Thomson Health Care. USPDI - Drug Information for the Health Care Professional. 22nd ed. Volume 1. MICROMEDEX Thomson Health Care, Greenwood Village, CO. 2002. Content Reviewed and Approved by the U.S. Pharmacopeial Convention, Inc., p. 2483
IN EXPERIMENTAL ANIMALS, QUINIDINE HAS VERY SIGNIFICANT ATROPINE LIKE ACTION, BLOCKING EFFECTS OF VAGAL STIMULATION OR OF ACETYLCHOLINE. ... ALSO HAS ALPHA-ADRENERGIC BLOCKING PROPERTIES. THIS CAN CAUSE VASODILATATION &, VIA BARORECEPTORS, ACTIVE SYMPATHETIC EFFERENT ACTIVITY. TOGETHER, CHOLINERGIC BLOCKAGE & INCR BETA-ADRENERGIC ACTIVITY CAUSED BY QUINIDINE CAN INCR SINUS RATE & ENHANCE ATRIOVENTRICULAR NODAL CONDUCTION. /QUINIDINE/
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 851
CAN CAUSE SEVERE DEPRESSION OF SINUS NODE IN PATIENTS WITH THE SICK SINUS SYNDROME ... QUINIDINE CAN INCR SINUS RATE BY CHOLINERGIC BLOCKADE OR BY REFLEXLY INCR SYMPATHETIC ACTIVITY. ... THERAPEUTIC CONCN OF QUINIDINE ... DECR FIRING RATE OF CARDIAC PURKINJE FIBERS BY DIRECT ACTION ... DECR SLOPE OF PHASE 4 DEPOLARIZATION AND SHIFTS THRESHOLD VOLTAGE TOWARD ZERO. /QUINIDINE/
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 850
... INCR DIASTOLIC ELECTRICAL CURRENT THRESHOLD IN ATRIAL & VENTRICULAR MUSCLE & IN PURKINJE FIBERS ... ALSO INCR FIBRILLATION THRESHOLD IN ATRIA & VENTRICLES. /QUINIDINE/
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 850
REENTRANT ARRYTHMIAS ARE ABOLISHED BY /QUINIDINE/. THEIR EFFECT ON EFFECTIVE REFRACTORY PERIOD, RESPONSIVENESS, & CONDUCTION. FOR EXAMPLE, WHEN VENTRICULAR PREMATURE DEPOLARIZATIONS ARE CAUSED BY REENTRY IN LOOPS OF PURKINJE FIBERS, ONE WAY BLOCK CAN BE CONVERTED TO TWO WAY BLOCK, THUS MAKING REENTRY IMPOSSIBLE. /QUINIDINE/
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 850
For more Mechanism of Action (Complete) data for QUINIDINE SULFATE (9 total), please visit the HSDB record page.

8.9 Human Metabolite Information

8.9.1 Cellular Locations

  • Extracellular
  • Membrane

8.9.2 Metabolite Pathways

8.10 Transformations

9 Use and Manufacturing

9.1 Uses

Sources/Uses
Used as a human and veterinary antiarrhythmic and human antimalarial; [Merck Index]
Merck Index - O'Neil MJ, Heckelman PE, Dobbelaar PH, Roman KJ (eds). The Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals, 15th Ed. Cambridge, UK: The Royal Society of Chemistry, 2013.
MEDICATION
MEDICATION (VET)

Use (kg; approx.) in Germany (2009): >500

Use (kg) in USA (2002): 56800

Consumption (g per capita; approx.) in Germany (2009): 0.00611

Consumption (g per capita) in the USA (2002): 0.201

Calculated removal (%): 41.8

9.1.1 Use Classification

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients
Pharmaceuticals
S72 | NTUPHTW | Pharmaceutically Active Substances from National Taiwan University | DOI:10.5281/zenodo.3955664

9.2 Methods of Manufacturing

ISOMERIZATION OF QUININE SULFATE
SRI
Quinidine may be made by treating quinine with a metallic alkoxide or by oxidizing quinine to quinone and then reducing the latter with sodium isopropoxide. It may also be obtained directly from the mother liquors remaining after removal of quinine from extracts of Cinchona; separation from cinchonine and other alkaloids is effected by special processes
GENNARO. REMINGTON'S PHARM SCI 17TH ED p.860 (1985)

9.3 Impurities

Quinidine of commerce is usually accompanied by up to 20% of hydroquinidine.
GENNARO. REMINGTON'S PHARM SCI 17TH ED p.860 (1985)
Commercially available quinidine salts contain not more than 20% of the respective dihydroquinidine salt, 1% of the respective quinine salt, and 1% of the respective dihydroquinine salt as impurities.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1571
Commercially available quinidine salts contain not more than 20% of the respective dihydroquinidine salt, 1% of the respective quinine salt, and 1% of the respective dihydroquinine salt as impurities. /Quinidine/
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 992

9.4 Formulations / Preparations

/Available as/ Capsules: 200and 300 mg; Injection: 200 mg/ml; Tablets: 100, 200 and 300 mg; Sustained-Release Tablets: 300 mg /Quinidine sulfate/, as Injection: 800 mg/10 ml; Extended-Release Tablets: 324 and 330 mg /Quinidine Gluconate/ and as Tablets: 275 mg /Quinidine Polygalacturonate/
GENNARO. REMINGTON'S PHARM SCI 17TH ED p.860 (1985)
Quinaglute Dura-Tabs contain 5 gr quinidine gluconate /per tablet/
GOSSELIN. CTCP 5TH ED p.V-528 (1984)
Quinidex Exten-tabs contain 300 mg quinidine sulfate /per tablet/
GOSSELIN. CTCP 5TH ED p.V-528 (1984)
Duraquin contains 330 mg quindine gluconate /per tablet/
BARNHART. PDR PHYSICIAN'S DESK REF 36TH ED p.1342 (1986)
For more Formulations/Preparations (Complete) data for QUINIDINE (11 total), please visit the HSDB record page.
QUINIDINE SULFATE CONTAINS 82% OF QUINIDINE BASE BY WEIGHT ... .
Miller, R. R., and D. J. Greenblatt. Handbook of Drug Therapy. New York: Elsevier North Holland, 1979., p. 301
QUINIDINE SULFATE AVAILABLE ... CAPSULES, CONTAIN 100 ... MG OF THE DRUG; TABLETS OF QUINIDINE POLYGALACTURONATE CONTAIN 275 MG, EQUIVALENT TO 200 MG OF QUINIDINE SULFATE. PREPN FOR SLOW ABSORPTION ARE ALSO AVAILABLE AS 300 MG EXTENDED RELEASE TABLET OF QUINIDINE SULFATE & A 324 MG TABLET OF GLUCONATE. QUINIDINE SULFATE IS ALSO AVAILABLE AS AN INJECTION IN 1 ML AMPULE CONTAINING 200 MG/ML. THE NECESSARY DOSE IS DILUTED TO 800 MG/50 ML IN 5% GLUCOSE SOLUTION AND IS INJECTED AT THE RATE OF 16 MG/MIN, WITH CONTINUOUS OBSERVATION OF THE PATIENT & OF THE ECG.
Gilman, A. G., L. S. Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co., Inc. 1980., p. 771
Oral Tablets extended release 324 mg (equivalent to quinidine 202 mg), Quinaglute Dura-Tabs, Berlex, Quinatime, CMC; 330 mg (equivalent to quinidine 206 mg), Duraquine (with povidone), Warner Chilcott; Parenteral injection, 80 mg (equivalent to quinidine 50 mg) per ml, quinidine gluconate injection (with edetate disodium and phenol). Lilly /Quinidine Gluconate/
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 997
Oral Tablets 275 mg (equivalent to quinidine sulfate 200 mg), Cardioquin (with povidone; scored), Purdue Frederick. /Quinidine polygalacturonate/
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 997
For more Formulations/Preparations (Complete) data for QUINIDINE SULFATE (7 total), please visit the HSDB record page.

9.5 Consumption Patterns

100% AS A CARDIAC DEPRESSANT TO INHIBIT AURICULAR FIBRILLATION (1975)
SRI

9.6 U.S. Production

(1972) PROBABLY GREATER THAN 4.54X10+5 GRAMS
SRI

9.7 U.S. Imports

(1984) 3.37X10+9 g /QUINIDINE AND ITS SALTS/
BUREAU OF THE CENSUS. U.S. IMPORTS FOR CONSUMPTION AND GENERAL IMPORTS 1984 p.1-365

9.8 General Manufacturing Information

EPA TSCA Commercial Activity Status
Cinchonan-9-ol, 6'-methoxy-, (9S)-: INACTIVE
Most of the material sold today is made by isomerization of quinine.
Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 1282
A long acting quinidine preparation /Quinidine gluconate/
Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 1283

10 Identification

10.1 Analytic Laboratory Methods

Analyte: quinidine gluconate; matrix: chemical identification; procedure: thin-layer chromatography with detection using short- and long-wavelength ultraviolet light and comparison to standards /Quinidine gluconate/
U.S. Pharmacopeia. The United States Pharmacopeia, USP 26/The National Formulary, NF 21; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p1605 (2003)
HPLC AND THIN LAYER CHROMATOGRAPHY DETERMINATIONS OF QUINIDINE AND RELATED ALKALOIDS IN PHARMACEUTICALS.
POUND NJ, SEARS RW; CAN J PHARM SCI 10 (4): 122-6 (1975)
Analyte: quinidine gluconate; matrix: chemical identification; procedure: solution in dilute sulfuric acid exhibits vivid blue fluorescence, addition of hydrochloric acid, the fluorescenece disappears. /Quinidine gluconate/
U.S. Pharmacopeia. The United States Pharmacopeia, USP 26/The National Formulary, NF 21; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p1605 (2003)
Analyte: quinidine gluconate; matrix: chemical purity; procedure: potentiometric titration with comparison to standards /Quinidine gluconate/
U.S. Pharmacopeia. The United States Pharmacopeia, USP 26/The National Formulary, NF 21; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p1605 (2003)
For more Analytic Laboratory Methods (Complete) data for QUINIDINE (10 total), please visit the HSDB record page.

10.2 Clinical Laboratory Methods

QUININE OR QUINIDINE DETECTION IN URINE BY FLUORESCENCE ANALYSIS, TLC.
Sunshine, Irving (ed.) Methodology for Analytical Toxicology. Cleveland: CRC Press, Inc., 1975., p. 336
QUINIDINE DETECTION IN PLASMA OR URINE BY UV SPECTROPHOTOMETRY WITH TLC CONFIRMATION.
Sunshine, Irving (ed.) Methodology for Analytical Toxicology. Cleveland: CRC Press, Inc., 1975., p. 338
GCD OF QUINIDINE IN BLOOD, PLASMA. OVERALL RECOVERY IS 98.27 + OR - 3.61%.
Sunshine, Irving (ed.) Methodology for Analytical Toxicology. Cleveland: CRC Press, Inc., 1975., p. 340
DETERMINATION OF QUINIDINE AND DIHYDROQUINIDINE IN PLASMA BY HPLC.
KLINE BJ ET AL; ANAL CHEM 51 (MAR): 449-51 (1979)
GLC DETERMINATION OF QUINIDINE FROM PLASMA AND WHOLE BLOOD. THE LIMIT OF DETECTABILITY IS 0.05 UG/ML OF QUINIDINE IN PLASMA AND THE METHOD IS ADEQUATE FOR FOLLOWING BLOOD PROFILES OF 200 MG QUINIDINE SULFATE DOSES IN HUMANS.
MIDHA KK, CHARETTE C; J PHARM SCI 63 (8): 1244 (1974)
QUINIDINE WAS DETERMINED IN PLASMA AFTER IV INJECTION OF QUINIDINE SULFATE (12.5 & 25 MG/KG AS QUINIDINE BASE) INTO RATS. THE UNCHANGED QUINIDINE WAS DETERMINED BY SPECTROFLUORODENSITOMETRY, EXCITATION AND EMISSION AT 350 AND 450 NM.
KOSKAS JP ET AL; J PHARM BELG 36 (3): 187 (1981)

11 Safety and Hazards

11.1 Hazards Identification

11.1.1 GHS Classification

Pictogram(s)
Acute Toxic
Irritant
Signal
Danger
GHS Hazard Statements

H301 (98%): Toxic if swallowed [Danger Acute toxicity, oral]

H315 (10%): Causes skin irritation [Warning Skin corrosion/irritation]

H319 (10%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H335 (10%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

Precautionary Statement Codes

P261, P264, P264+P265, P270, P271, P280, P301+P316, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 50 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

11.1.2 Hazard Classes and Categories

Acute Tox. 3 (98%)

Skin Irrit. 2 (10%)

Eye Irrit. 2A (10%)

STOT SE 3 (10%)

11.1.3 Health Hazards

SYMPTOMS: Symptoms of exposure to this compound may include anorexia, nausea, vomiting, abdominal cramps, diarrhea, tinnitus, impaired hearing, blurred vision, vertigo, severe emotional reactions, pyrexia, skin eruptions, thrombocytopenic purpura, asthma, urticaria, acute hemolytic anemia, heart block, diminished cardiac output, ventricular tachycardia, ventricular fibrillation or acute ventricular asystole, headache, confusion, skin rash and angioedema.

ACUTE/CHRONIC HAZARDS: This compound can cause irritation of the skin, eyes and mucous membranes. When heated to decomposition it emits toxic fumes. (NTP, 1992)

National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

11.1.4 Fire Hazards

Flash point data for this compound are not available. It is probably combustible. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

11.1.5 Hazards Summary

Quinidine sulfate has elicited contact allergy in production workers, and patch test with quinine were negative. [Kanerva, p. 435] Quinidine may induce photosensitivity in patients taking it systemically (photodrug reaction). [Marks, p. 201-3] As an oral medication, quinidine is used to treat heart arrhythmias. Many side effects have been reported after ingestion of therapeutic doses, including immune hemolytic anemia and drug-induced hepatitis. [HSDB] Therapeutic serum levels are 2-4 mg/L, and serious adverse effects are unusual in that range. A one gram dose is potentially lethal to adults. Toxic effects include ventricular tachycardia and depression of cardiac contractility. Other symptoms are vomiting, diarrhea, and anticholinergic effects. Seizures and coma may follow. Symptoms of chronic poisoning (cinchonism) are tinnitus, vertigo, deafness, and visual disturbances. [Olson, p. 398-9]
Kanerva - Rustemeyer L, Elsner P, John SM, Maibach HI (eds). Kanerva's Occupational Dermatology, 2nd Ed. Berlin: Springer-Verlag, 2012., p. 435
Marks - Marks JG, DeLeo VA. Contact and Occupational Dermatology, 2nd Ed. St. Louis: Mosby, 1997., p. 201-3
Olson - Olson KR (ed). Poisoning & Drug Overdose, 7th Ed. New York: Lange Medical Books/McGraw-Hill, 2018., p. 398-9

11.2 First Aid Measures

11.2.1 First Aid

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment.

INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing.

INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

11.3 Fire Fighting

Fires involving this compound can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

11.4 Accidental Release Measures

11.4.1 Isolation and Evacuation

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]:

IMMEDIATE PRECAUTIONARY MEASURE: Isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids.

SPILL: Increase the immediate precautionary measure distance, in the downwind direction, as necessary.

FIRE: If tank, rail tank car or highway tank is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2024)

11.4.2 Cleanup Methods

If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for disposal Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the comtaminated area until safty officer has verified that the area has been properly cleaned.
DHHS/National Toxicology Program; Chemical Health & Safety Data File. Available from: https://ntp-db.niehs.nih.gov/cgi/iH_Indexes/Chem_H&S/iH_Chem_H&S_Frames.html on quinidine; 56-54-2 as January 17, 2003

11.4.3 Disposal Methods

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

11.5 Handling and Storage

11.5.1 Nonfire Spill Response

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

STORAGE PRECAUTIONS: You should store this material in a refrigerator. (NTP, 1992)

National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

11.5.2 Storage Conditions

Quinidine should be stored at controlled room temperature. Quinidine salts slowly discolor on exposure to light, aquiring a brownish tint. Only clear, colorless solutions are suitable for injection./intravenous quinidine gluconate/
Trissel, L.A. Handbook on Injectable Drugs. 9th ed. Bethesda, MD. American Society of Health-System Pharmacists' Product Development. 1996., p. 957
You should store this material in the refrigerator.
DHHS/National Toxicology Program; Chemical Health & Safety Data File. Available from: https://ntp-db.niehs.nih.gov/cgi/iH_Indexes/Chem_H&S/iH_Chem_H&S_Frames.html on quinidine; 56-54-2 as January 17, 2003

11.6 Exposure Control and Personal Protection

11.6.1 Personal Protective Equipment (PPE)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

11.7 Stability and Reactivity

11.7.1 Air and Water Reactions

Insoluble in water.

11.7.2 Reactive Group

Alcohols and Polyols

Amines, Phosphines, and Pyridines

Hydrocarbons, Aliphatic Unsaturated

11.8 Transport Information

11.8.1 DOT Label

Poison

11.9 Regulatory Information

REACH Registered Substance

11.9.1 CERCLA Reportable Quantities

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 5,000 lb or 2270 kg. The toll- free- telephone number of the NRC is (800) 424-8802; in the Washington metropolitan area (202) 426-2675. The rule for determining when notification is required is stated in 40 CFR 302.6 (see section IV. D.3.b).
50 FR 13456 (4/14/85)

11.9.2 FDA Requirements

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl quinidine gluconate and quinidine sulfate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Quinidine gluconate and quinidine sulfate/
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of July 1, 2003: https://www.fda.gov/cder/ob/
Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).
21 CFR 200-299, 300-499, 820, and 860; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of July 1, 2003: https://www.ecfr.gov
21 CFR 200-299, 300-499, 820, and 860 (4/1/91)
The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl quinidine sulfate, approved on the basis of safety and effectiveness by FDA under sections 505 and 507 of the Federal Food, Drug, and Cosmetic Act.
DHHS/FDA; Approved Drug Products with Therapeutic Equivalence Evaluations 12th edition p.3-243 (1992)

11.10 Other Safety Information

Chemical Assessment

IMAP assessments - Cinchonan-9-ol, 6'-methoxy-, (9S)-: Environment tier I assessment

IMAP assessments - Cinchonan-9-ol, 6'-methoxy-, (9S)-: Human health tier I assessment

11.10.1 Special Reports

Anderson JL; Clinical Implications of New Studies in the Treatment of Benign, Potentially Malignant and Malignant Ventricular Arrhythmias. Am J Cardiol 65 (4): 36B-42B (1990). For purposes of clinical management, ventricular arrhythmias have been divided into risk categories of benign, prognostically important (potentially malignant) and malignant. For malignant arrhythmias, class IA agents (procainamide and quinidine) continue to be the standard of treatment.
Kim SY, Benowitz NL; Poisoning Due to Class IA Antiarrhythmic Drugs: Quinidine, Procainamide and Disopyramide. Drug Saf 5 (Nov-Dec): 393-420 (1990). A review of poisoning due to quinidine is presented, including the mechanism of toxicity, clinical features, pharmacokinetics, drug interactions, and clinical management with sodium bicarbonate and potassium and accelerated drug removal with dialysis.
Kirchbaum DW; Combination Drug Therapy for Ventricular Arrhythmias. Clin Pharm 7(Nov): 808-19 (1988). The use of combined therapy with antiarrhythmic agents in patients with ventricular arrhythmias in whom single drug therapy has been ineffective or poorly tolerated is reviewed. Pairs of drugs showing the most promise have been a class IA drug (procainamide, quinidine or disopyramide) with a class IB drug (usually mexiletine) or a class IA drug with a beta-blocker.
Knobler H et al; Quinidine Induced Hepatitis: Common and Reversible Hypersensitivity Reaction. Arch Intern Med 146 (Mar): 526-8 (1986). A review of 33 cases of hepatitis attributed to quinidine occurring over a 10 yr period at one hospital was presented. Clinical and histological features of the syndrome were described. A hypersensitivity mechanism was suggested for the reaction.
Huang SK, Marcus FI; Antiarrhythmic Drug Therapy of Ventricular Arrhythmias. Curr Probl Cardiol 11 (4): 177-240 (1986). Congestive heart failure is associated with hypoperfusion to various organs including the sites of drug clearance, ie the liver and kidneys. It also leads to organ congestion as seen in the liver and gut. Not all adverse reactions to drugs that may occur in heart failure are the result of alterations in pharmacokinetics; rather, some may be due to important drug interactions. An interaction may occur directly eg reduction of renal clearance of digoxin by captopril and quinidine; or indirectly, e.g., through diuretic induced hypokalemia, which exacerbate arrhythmias associated with digoxin and antiarrhythmics such as quinidine and procainamide.
Anderson JL; Clinical implications of New Studies in the Treatment of Benign, Potentially Malignant and Malignant Ventricular Arrhythmias. Am J Cardiol 65 (4): 36B-42B (1990). For purposes of clinical management, ventricular arrhythmias have been divided into risk categories of benign, prognostically important (potentially malignant) and malignant. For malignant arrhythmias, class IA agents (procainamide and quinidine) continue to be the standard of treatment. /Quinidine/
Kim SY, Benowitz NL; Poisoning Due to Class IA Antiarrhythmic Drugs: Quinidine, Procainamide and Disopyramide. Drug Saf 5 (Nov-Dec): 393-420 (1990). A review of poisoning due to quinidine is presented, including the mechanism of toxicity, clinical features, pharmacokinetics, drug interactions, and clinical management with sodium bicarbonate and potassium and accelerated drug removal with dialysis. /Quinidine/
Kirchbaum DW; Combination Drug Therapy for Ventricular Arrhythmias. Clin Pharm 7(Nov): 808-19 (1988). The use of combined therapy with antiarrhythmic agents in patients with ventricular arrhythmias in whom single drug therapy has been ineffective or poorly tolerated is reviewed. Pairs of drugs showing the most promise have been a class IA drug (procainamide, quinidine or disopyramide) with a class IB drug (usually mexiletine) or a class IA drug with a beta blocker. /Quinidine/
Knobler H et al; Quinidine Induced Hepatitis: Common and Reversible Hypersensitivity Reaction. Arch Intern Med 146 (Mar): 526-8 (1986). A review of 33 cases of hepatitis attributed to quinidine occurring over a 10 yr period at one hospital was presented. Clinical and histological features of the syndrome were described. A hypersensitivity mechanism was suggested for the reaction. /Quinidine/
Huang SK, Marcus FI; Antiarrhythmic Drug Therapy of Ventricular Arrhythmias. Curr Probl Cardiol 11 (4): 177-240 (1986). Congestive heart failure is associated with hypoperfusion to various organs including the sites of drug clearance, ie the liver and kidneys. It also leads to organ congestion as seen in the liver and gut. Not all adverse reactions to drugs that may occur in heart failure are the result of alterations in pharmacokinetics; rather, some may be due to important drug interactions. An interaction may occur directly eg reduction of renal clearance of digoxin by captopril and quinidine; or indirectly, eg through diuretic induced hypokalemia, which exacerbate arrhythmias associated with digoxin and antiarrhythmics such as quinidine and procainamide. /Quinidine/

12 Toxicity

12.1 Toxicological Information

12.1.1 Toxicity Summary

IDENTIFICATION: Quinidine is a class lA antiarrhythmic drug. Origin of the substance: Quinidine is the d- isomer of quinine. Quinidine is an alkaloid that may be derived from various species of Cinchona. Cinchona barks contain 0.25 to 3.0% quinidine. Quinidine is also prepared from quinine. Quinidine is a powder or white crystals, odorless with a bitter taste. Quinidine bisulfate is colorless crystals which is odorless and has a bitter taste. Quinidine gluconate is a white powder which is odorless and has a bitter taste. Quinidine poly-galacturonate is a powder. Quinidine sulfate is a white powder or odorless crystals with a bitter taste. Indications: Description: Premature ventricular extrasystoles and ventricular tachycardia; supraventricular arrhythmia; maintenance of sinus rhythm after cardioversion of atrial flutter or fibrillation. HUMAN EXPOSURE: Main risks and target organs: Cardio-toxicity is the main risk of quinidine poisoning. Quinidine may induce central nervous system symptoms. Summary of clinical effects: Toxic effects appear within 2 - 4 hours after ingestion but the delay may vary according to the quinidine salt and to the preparation forms. Symptoms may include disturbances of cardiac rhythm (especially in patients with underlying cardiovascular disease), neurotoxicity and respiratory depression. Diagnosis: Cardiac disturbances: circulatory arrest, shock, conduction disturbances, ventricular arrhythmias, ECG changes, Neurological symptoms: tinnitus, drowsiness, syncope, coma, convulsions, delirium. Respiratory depression. Quinidine concentrations may be helpful in diagnosis but are not useful for clinical management. Contraindications: Allergy or idiosyncrasy to cinchona alkaloids; atrioventricular or complete heart block; intraventricular conduction defects; absence of atrial activity; digitalis intoxication; myasthenia gravis and ventricular dysrhythmia of the torsades de pointes type Precautions include the following: Congestive heart failure, hypotension, renal disease, hepatic failure; concurrent use of other antiarrhythmic drugs; old age and breast-feeding. Routes of entry: Oral: Oral absorption is the most frequent cause of intoxication. Parenteral: Intoxication after IV administration is rare but has been reported in patients treated with IV quinidine for cardiac dysrhythmia. Absorption by route of exposure: Oral: Quinidine is almost completely absorbed from the gastrointestinal tract. However, because of hepatic first-pass effect, the absolute bioavailability is about 70 to 80% of the ingested dose and may vary between patients and preparations. The time to plasma peak concentration is 1 to 3 hours for quinidine sulfate, 3 to 6 hours for quinidine gluconate and about 6 hours for quinidine polygalacturonate. Sustained-release quinidine is absorbed continuously over 8 to 12 hours. Parenteral: Absorption of quinidine after intramuscular injection may be erratic and unpredictable with incomplete absorption of the administered dose, probably due to precipitation of drug at the site of injection. Other studies indicate no difference between the rate of quinidine absorption when given by intramuscular injection or oral absorption. Distribution by route of exposure: Oral: Protein binding: About 70 to 80% of the drug is bound to plasma protein. Plasma protein binding is decreased in patients with chronic liver disease. Tissue: Quinidine concentrations in liver are 10 to 30 times higher than those in plasma. Skeletal and cardiac muscle, brain and other tissues contain intermediate amounts. The red cell plasma partition ratio is 0.82. Biological half-life by route of exposure: Elimination half-life: The half-life is about 6 to 7 hours. It is increased in chronic liver disease and in the elderly. It does not appear to be altered in congestive heart failure or renal failure. Metabolism: 50 to 90% of quinidine is metabolized in the liver to hydroxylated products. Metabolites include 3-hydroxyquinidine, 2 oxoquinidinone, 0-desmethylquinidine, quinidine-N-oxide. The principal metabolite is 3 hydroxyquinidine which exerts similar effects to quinidine and may account for part of the observed antiarrhythmic effects. The elimination kinetics of hydroxyquinidine appear to be similar to those of quinidine. Elimination by route of exposure Kidney: The amount excreted unchanged in urine is variable but is about 17% of an administered dose. Up to 50% of a dose of quinidine (unchanged + metabolites) is excreted in urine within 24 hours after administration. Renal excretion is dependent upon the pH of the urine. Excretion varies inversely with urine pH. Excretion is reduced in renal insufficiency and in congestive heart failure. Liver: 50 to 90% of a dose of quinidine is metabolized in the liver. Bile: Approximately 1 to 3% is excreted in the feces via the bile. Breast milk: Quinidine is excreted in breast milk. Mode of action Toxicodynamics: Quinidine reduces the permeability of heart muscle to electrolytes (membrane stabilizer) and is a general cardiac depressant. It has a negative inotropic effect; inhibits the spontaneous diastolic depolarization; slow conduction; lengthens the effective refractory period; and raises the electrical threshold. This results in depression of contractility, impaired conductivity (atrioventricular and intraventricular) and decreased excitability but with possible abnormal stimulus re-entry mechanism. Quinidine has an anticholinergic effect and peripheral vasodilator properties. In experimental studies the following progression changes was observed: ECG: bradycardia, prolongation of the PR interval, lengthening of the QT interval, widening of the QRS with development of an idioventricular rhythm and then in ventricular standstill. Sometimes the terminal event was ventricular fibrillation. Blood pressure decreases progressively. A significant decrease of blood pressure was noted with the appearance of QRS widening and blood pressure was close to zero when slow idioventricular rhythm appeared. Electrolytes abnormalities: decrease in plasma concentrations of potassium, sodium and magnesium with the development of acidosis. Electrolytes: Hypokalaemia may occur and is probably related to an intracellular transport of potassium by a direct effect on cellular membrane permeability. Neurologic symptoms: Syncope and convulsions may represent a direct toxic effect on CNS or may be related to cerebral ischaemia due to circulatory or respiratory failure. Pharmacodynamics: Quinidine slows the rate of firing of the normal and of ectopic rhythmic foci; it raises the threshold for electrically induced arrhythmias; it protects against ventricular arrhythmias; and it prevents or terminates circus movement flutter. Teratogenicity: Quinidine has been implicated as a cause of light cranial nerve damage to the fetus at doses much larger than those needed to treat arrhythmias. Interactions: Several interactions have been reported. Quinidine has a synergistic action with warfarin (decrease of prothrombin level). Quinidine potentiates both non-depolarizing and depolarizing neuromuscular blocking agents. The cardiodepressant effects of other antiarrhythmic agents are increased by concurrent use of quinidine; amiodarone increases quinidine concentrations in the blood. Quinidine concentrations are reduced by: rifampicin, anticonvulsants, nifedipine and acetazolamide. Quinidine concentrations are increased by antacids, cimetidine, verapamil and amiodarone; the risk of quinidine toxicity is increased by terfenadine, astemizole, and thiazide and loop diuretics. Quinidine increases the plasma concentrations of propafenone and digoxin. Main adverse effects: Numerous adverse effects during quinidine therapy have been reported. Cardiovascular: Hypotension after IV administration; Syncope; proarrhythmic effect: "torsades de pointes"; and ECG: widening of QRS interval; prolongation of PR and QT intervals. CNS: Cinchonism: headache, fever, visual disturbances, mydriasis, tinnitus, nausea, vomiting and rashes. Gastrointestinal: Nausea, vomiting, diarrhoea, colic have been reported. Hepatic: Granulomatous hepatitis or hepatitis with centrilobular necrosis. Skin: Skin rashes with drug fever and photosensitivity may result. Hematologic: Thrombocytopenia (immunologic reaction) has been noted. Clinical effects: Acute poisoning: Ingestion: Severity of quinidine poisoning is related to the cardiotoxic effects. Symptoms appear usually within 2 to 4 hours and may include: cardiovascular symptoms: hypotension, cardiogenic shock, cardiac arrest. ECG may show: decrease of T wave; prolongation of QT and QRS intervals; atrioventricular block; ventricular dysrhythmia (torsade de pointes). Neurological symptoms: tinnitus, drowsiness, syncope, coma, convulsion, blurred vision and diplopia. Respiratory symptoms: hypoventilation and apnea. Cardiotoxicity may be enhanced if other cardiotoxic drugs have been ingested (antiarrhythmic drugs, tricyclic antidepressants). Parenteral exposure: After IV administration symptoms appear more rapidly. Chronic poisoning: Ingestion: The most relevant symptoms of chronic poisoning are: ECG disturbances; syncope due to ventricular dysrhythmia, (torsade de pointes) and cinchonism gastrointestinal disturbances Course, prognosis, cause of death: The usual course of quinidine poisoning is dominated by the cardiovascular disturbances which usually occur within 2 to 4 first hours but may first appear as late as 12 hours after exposure (and perhaps even later after ingestion of a slow- release preparation). Symptoms may last for 24 to 36 hours. Patients who survive 48 hours after acute poisoning are likely to recover. Death may result from cardiac arrest by asystole or electromechanical dissociation and, rarely, by ventricular fibrillation. Systematic description of clinical effects: Cardiovascular: Acute: Cardiovascular symptoms are the major features of quinidine toxicity. Tachycardia due to anticholinergic effects is usually observed initially or in moderate intoxication. In severe intoxication, bradycardia due to atrioventricular block may occur. Hypotension and shock: hypotension due to peripheral vasodilation is common. In severe intoxication, cardiogenic shock with increased central venous pressure is usually observed and is related to decreased cardiac contractility. Cardiac arrest may occur, which may be related to electromechanical dissociation, ventricular dysrhythmia or asystole. Cardiac dysrhythmias are common and may include: atrioventricular block, idioventricular rhythm, ventricular tachycardia and fibrillation, torsades de pointes. ECG changes are always present in symptomatic intoxication: repolarization abnormalities, decreased T wave, increase of U wave, prolongation of QT and PR intervals, widening of QRS complexes (> 0.08 sec), atrioventricular block. Syncope due to torsade de pointes may occur. Chronic: ECG changes with repolarization abnormalities, decreased T wave and increase of QT interval are a common feature during quinidine therapy. Syncope is related to transient torsade de pointes and occurs in 1 to 8% of patients receiving quinidine. The occurrence of torsade de pointes is not correlated with plasma quinidine levels but is favored by an increase in the QT interval. Respiratory: Acute: Respiratory depression or apnea is mostly associated with severe cardiac disturbances such as shock or ventricular dysrhythmia. Pulmonary edema with normal pulmonary capillary wedge pressure following an attempted suicide has been documented. Neurological: CNS: Acute: Drowsiness, delirium, coma and convulsions may appear without cardiac symptoms. However, cardiac failure should always be considered when CNS symptoms appear. Cinchonism may sometimes appear. Chronic: Cinchonism. Delirium has been reported. Peripheral nervous system: Chronic: Quinidine can potentiate the neuromuscular blocking action of some skeletal muscle relaxants and may cause the return of respiratory paralysis if it is given shortly after recovery from neuromuscular blockade. Autonomic nervous system: Acute: Quinidine has an anticholinergic effect. However, this effect is usually limited to the vagal system. Skeletal and smooth muscle: Chronic: An increase in serum concentrations of skeletal muscle enzymes has been reported in a man treated with quinidine. Gastrointestinal: Acute: Nausea and vomiting may occur. Chronic: Gastrointestinal toxicity (nausea, vomiting, diarrhea and colic) is the most frequent side effect of quinidine. Hepatic: Chronic: Hepatotoxicity has been reported, with an increase in serum concentrations of transaminases, LDH, alkaline phosphatase, and cholestasis. Renal: Acute: No direct nephrotoxic effect has been reported. Acute renal failure related to cardiogenic shock may occur. Dermatological: Chronic: Skin lesions have been attributed to the use of quinidine and include skin rash, photosensitivity and lichen planus. Eye, ear, nose, throat: local effects: Acute: Cinchonism is rarely observed in acute poisonings. Toxic amblyopia, scotoma and impaired color perception may occur at toxic doses. Chronic: Chronic cumulative overdose may cause cinchonism: headache, tinnitus, vertigo, mydriasis, blurred vision, diplopia, photophobia, deafness, and corneal deposits have been reported in a patient who took quinidine for two years. Hematological: Chronic: Thrombocytopenia and hemolytic anemia of immunologic origins have been reported. Immunological: Chronic: Quinidine may cause several immunologic mediated reactions: thrombocytopenia, hemolytic anemia, angioneurotic edema, skin rash, fever. Metabolic: Acid-base disturbances: Acute: Metabolic acidosis may occur in severe intoxication with shock. Fluid and electrolyte disturbances: Acute: Hypokalemia is frequently observed. Special risks: Pregnancy: Chronic: Quinidine has been implicated as a cause of cranial nerve damage to the fetus at doses much larger than those needed to treat arrhythmia. In a neonate born to a woman taking quinidine throughout pregnancy, serum levels were equal to that of the mother. The child's ECG was normal and there was no evidence of teratogenicity. Breast-feeding: Chronic: Quinidine is present in breast milk at levels slightly lower than serum levels. The dose of quinidine received by an infant taking 1l of milk would be below therapeutic doses. However, breast-feeding is not recommended because of potential quinidine accumulation in the immature newborn liver.
International Programme on Chemical Safety; Poisons Information Monograph: Quinidine (PIM 463) (1990) Available from, as of April 7, 2009: https://www.inchem.org/pages/pims.html
IDENTIFICATION: Quinidine is a class lA antiarrhythmic drug. Origin of the substance: Quinidine is the d- isomer of quinine. Quinidine is an alkaloid that may be derived from various species of Cinchona. Cinchona barks contain 0.25 to 3.0% quinidine. Quinidine is also prepared from quinine. Quinidine is a powder or white crystals, odorless with a bitter taste. Quinidine bisulfate is colorless crystals which is odorless and has a bitter taste. Quinidine gluconate is a white powder which is odorless and has a bitter taste. Quinidine poly-galacturonate is a powder. Quinidine sulfate is a white powder or odorless crystals with a bitter taste. Indications: Description: Premature ventricular extrasystoles and ventricular tachycardia; supraventricular arrhythmia; maintenance of sinus rhythm after cardioversion of atrial flutter or fibrillation. HUMAN EXPOSURE: Main risks and target organs: Cardio-toxicity is the main risk of quinidine poisoning. Quinidine may induce central nervous system symptoms. Summary of clinical effects: Toxic effects appear within 2 - 4 hours after ingestion but the delay may vary according to the quinidine salt and to the preparation forms. Symptoms may include disturbances of cardiac rhythm (especially in patients with underlying cardiovascular disease), neurotoxicity and respiratory depression. Diagnosis: Cardiac disturbances: circulatory arrest, shock, conduction disturbances, ventricular arrhythmias, ECG changes, Neurological symptoms: tinnitus, drowsiness, syncope, coma, convulsions, delirium. Respiratory depression. Quinidine concentrations may be helpful in diagnosis but are not useful for clinical management. Contraindications: Allergy or idiosyncrasy to cinchona alkaloids; atrioventricular or complete heart block; intraventricular conduction defects; absence of atrial activity; digitalis intoxication; myasthenia gravis and ventricular dysrhythmia of the torsades de pointes type Precautions include the following: Congestive heart failure, hypotension, renal disease, hepatic failure; concurrent use of other antiarhythmic drugs; old age and breast-feeding. Routes of entry: Oral: Oral absorption is the most frequent cause of intoxication. Parenteral: Intoxication after IV administration is rare but has been reported in patients treated with IV quinidine for cardiac dysrhythmia. Absorption by route of exposure: Oral: Quinidine is almost completely absorbed from the gastrointestinal tract. However, because of hepatic first-pass effect, the absolute bioavailability is about 70 to 80% of the ingested dose and may vary between patients and preparations. The time to plasma peak concentration is 1 to 3 hours for quinidine sulfate, 3 to 6 hours for quinidine gluconate and about 6 hours for quinidine polygalacturonate. Sustained-release quinidine is absorbed continuously over 8 to 12 hours. Parenteral: Absorption of quinidine after intramuscular injection may be erratic and unpredictable with incomplete absorption of the administered dose, probably due to precipitation of drug at the site of injection. Other studies indicate no difference between the rate of quinidine absorption when given by intramuscular injection or oral absorption. Distribution by route of exposure: Oral: Protein binding: About 70 to 80% of the drug is bound to plasma protein. Plasma protein binding is decreased in patients with chronic liver disease. Tissue: Quinidine concentrations in liver are 10 to 30 times higher than those in plasma. Skeletal and cardiac muscle, brain and other tissues contain intermediate amounts. The red cell plasma partition ratio is 0.82. Biological half-life by route of exposure: Elimination half-life: The half-life is about 6 to 7 hours. It is increased in chronic liver disease and in the elderly. It does not appear to be altered in congestive heart failure or renal failure. Metabolism: 50 to 90% of quinidine is metabolized in the liver to hydroxylated products. Metabolites include 3-hydroxyquinidine, 2 oxoquinidinone, 0-desmethylquinidine, quinidine-N-oxide. The principal metabolite is 3 hydroxyquinidine which exerts similar effects to quinidine and may account for part of the observed antiarrhythmic effects. The elimination kinetics of hydroxyquinidine appear to be similar to those of quinidine. Elimination by route of exposure Kidney: The amount excreted unchanged in urine is variable but is about 17% of an administered dose. Up to 50% of a dose of quinidine (unchanged + metabolites) is excreted in urine within 24 hours after administration. Renal excretion is dependent upon the pH of the urine. Excretion varies inversely with urine pH. Excretion is reduced in renal insufficiency and in congestive heart failure. Liver: 50 to 90% of a dose of quinidine is metabolized in the liver. Bile: Approximately 1 to 3% is excreted in the feces via the bile. Breast milk: Quinidine is excreted in breast milk. Mode of action Toxicodynamics: Quinidine reduces the permeability of heart muscle to electrolytes (membrane stabilizer) and is a general cardiac depressant. It has a negative inotropic effect; inhibits the spontaneous diastolic depolarization; slow conduction; lengthens the effective refractory period; and raises the electrical threshold. This results in depression of contractility, impaired conductivity (atrioventricular and intraventricular) and decreased excitability but with possible abnormal stimulus re-entry mechanism. Quinidine has an anticholinergic effect and peripheral vasodilator properties. In experimental studies the following progression changes was observed: ECG: bradycardia, prolongation of the PR interval, lengthening of the QT interval, widening of the QRS with development of an idioventricular rhythm and then in ventricular standstill. Sometimes the terminal event was ventricular fibrillation. Blood pressure decreases progressively. A significant decrease of blood pressure was noted with the appearance of QRS widening and blood pressure was close to zero when slow idioventricular rhythm appeared. Electrolytes abnormalities: decrease in plasma concentrations of potassium, sodium and magnesium with the development of acidosis. Electrolytes: Hypokalaemia may occur and is probably related to an intracellular transport of potassium by a direct effect on cellular membrane permeability. Neurologic symptoms: Syncope and convulsions may represent a direct toxic effect on CNS or may be related to cerebral ischaemia due to circulatory or respiratory failure. Pharmacodynamics: Quinidine slows the rate of firing of the normal and of ectopic rhythmic foci; it raises the threshold for electrically induced arrhythmias; it protects against ventricular arrhythmias; and it prevents or terminates circus movement flutter. Teratogenicity: Quinidine has been implicated as a cause of light cranial nerve damage to the fetus at doses much larger than those needed to treat arrhythmias. Interactions: Several interactions have been reported. Quinidine has a synergistic action with warfarin (decrease of prothrombin level). Quinidine potentiates both non-depolarizing and depolarizing neuromuscular blocking agents. The cardiodepressant effects of other antiarrhythmic agents are increased by concurrent use of quinidine; amiodarone increases quinidine concentrations in the blood. Quinidine concentrations are reduced by: rifampicin, anticonvulsants, nifedipine and acetazolamide. Quinidine concentrations are increased by antacids, cimetidine, verapamil and amiodarone; the risk of quinidine toxicity is increased by terfenadine, astemizole, and thiazide and loop diuretics. Quinidine increases the plasma concentrations of propafenone and digoxin. Main adverse effects: Numerous adverse effects during quinidine therapy have been reported. Cardiovascular: Hypotension after IV administration; Syncope; proarrhythmic effect: "torsades de pointes"; and ECG: widening of QRS interval; prolongation of PR and QT intervals. CNS: Cinchonism: headache, fever, visual disturbances, mydriasis, tinnitus, nausea, vomiting and rashes. Gastrointestinal: Nausea, vomiting, diarrhoea, colic have been reported. Hepatic: Granulomatous hepatitis or hepatitis with centrilobular necrosis. Skin: Skin rashes with drug fever and photosensitivity may result. Hematologic: Thrombocytopenia (immunologic reaction) has been noted. Clinical effects: Acute poisoning: Ingestion: Severity of quinidine poisoning is related to the cardiotoxic effects. Symptoms appear usually within 2 to 4 hours and may include: cardiovascular symptoms: hypotension, cardiogenic shock, cardiac arrest. ECG may show: decrease of T wave; prolongation of QT and QRS intervals; atrioventricular block; ventricular dysrhythmia (torsade de pointes). Neurological symptoms: tinnitus, drowsiness, syncope, coma, convulsion, blurred vision and diplopia. Respiratory symptoms: hypoventilation and apnea. Cardiotoxicity may be enhanced if other cardiotoxic drugs have been ingested (antiarrhythmic drugs, tricyclic antidepressants). Parenteral exposure: After IV administration symptoms appear more rapidly. Chronic poisoning: Ingestion: The most relevant symptoms of chronic poisoning are: ECG disturbances; syncope due to ventricular dysrhythmia, (torsade de pointes) and cinchonism gastrointestinal disturbances Course, prognosis, cause of death: The usual course of quinidine poisoning is dominated by the cardiovascular disturbances which usually occur within 2 to 4 first hours but may first appear as late as 12 hours after exposure (and perhaps even later after ingestion of a slow- release preparation). Symptoms may last for 24 to 36 hours. Patients who survive 48 hours after acute poisoning are likely to recover. Death may result from cardiac arrest by asystole or electromechanical dissociation and, rarely, by ventricular fibrillation. Systematic description of clinical effects: Cardiovascular: Acute: Cardiovascular symptoms are the major features of quinidine toxicity. Tachycardia due to anticholinergic effects is usually observed initially or in moderate intoxication. In severe intoxication, bradycardia due to atrioventricular block may occur. Hypotension and shock: hypotension due to peripheral vasodilation is common. In severe intoxication, cardiogenic shock with increased central venous pressure is usually observed and is related to decreased cardiac contractility. Cardiac arrest may occur, which may be related to electromechanical dissociation, ventricular dysrhythmia or asystole. Cardiac dysrhythmias are common and may include: atrioventricular block, idioventricular rhythm, ventricular tachycardia and fibrillation, torsades de pointes. ECG changes are always present in symptomatic intoxication: repolarization abnormalities, decreased T wave, increase of U wave, prolongation of QT and PR intervals, widening of QRS complexes (> 0.08 sec), atrioventricular block. Syncope due to torsade de pointes may occur. Chronic: ECG changes with repolarization abnormalities, decreased T wave and increase of QT interval are a common feature during quinidine therapy. Syncope is related to transient torsade de pointes and occurs in 1 to 8% of patients receiving quinidine. The occurrence of torsade de pointes is not correlated with plasma quinidine levels but is favored by an increase in the QT interval. Respiratory: Acute: Respiratory depression or apnea is mostly associated with severe cardiac disturbances such as shock or ventricular dysrhythmia. Pulmonary edema with normal pulmonary capillary wedge pressure following an attempted suicide has been documented. Neurological: CNS: Acute: Drowsiness, delirium, coma and convulsions may appear without cardiac symptoms. However, cardiac failure should always be considered when CNS symptoms appear. Cinchonism may sometimes appear. Chronic: Cinchonism. Delirium has been reported. Peripheral nervous system: Chronic: Quinidine can potentiate the neuromuscular blocking action of some skeletal muscle relaxants and may cause the return of respiratory paralysis if it is given shortly after recovery from neuromuscular blockade. Autonomic nervous system: Acute: Quinidine has an anticholinergic effect. However, this effect is usually limited to the vagal system. Skeletal and smooth muscle: Chronic: An increase in serum concentrations of skeletal muscle enzymes has been reported in a man treated with quinidine. Gastrointestinal: Acute: Nausea and vomiting may occur. Chronic: Gastrointestinal toxicity (nausea, vomiting, diarrhea and colic) is the most frequent side effect of quinidine. Hepatic: Chronic: Hepatotoxicity has been reported, with an increase in serum concentrations of transaminases, LDH, alkaline phosphatase, and cholestasis. Renal: Acute: No direct nephrotoxic effect has been reported. Acute renal failure related to cardiogenic shock may occur. Dermatological: Chronic: Skin lesions have been attributed to the use of quinidine and include skin rash, photosensitivity and lichen planus. Eye, ear, nose, throat: local effects: Acute: Cinchonism is rarely observed in acute poisonings. Toxic amblyopia, scotoma and impaired color perception may occur at toxic doses. Chronic: Chronic cumulative overdose may cause cinchonism: headache, tinnitus, vertigo, mydriasis, blurred vision, diplopia, photophobia, deafness, and corneal deposits have been reported in a patient who took quinidine for two years. Hematological: Chronic: Thrombocytopenia and hemolytic anemia of immunologic origins have been reported. Immunological: Chronic: Quinidine may cause several immunologic mediated reactions: thrombocytopenia, hemolytic anemia, angioneurotic edema, skin rash, fever. Metabolic: Acid-base disturbances: Acute: Metabolic acidosis may occur in severe intoxication with shock. Fluid and electrolyte disturbances: Acute: Hypokalemia is frequently observed. Special risks: Pregnancy: Chronic: Quinidine has been implicated as a cause of cranial nerve damage to the fetus at doses much larger than those needed to treat arrhythmia. In a neonate born to a woman taking quinidine throughout pregnancy, serum levels were equal to that of the mother. The child's ECG was normal and there was no evidence of teratogenicity. Breast-feeding: Chronic: Quinidine is present in breast milk at levels slightly lower than serum levels. The dose of quinidine received by an infant taking 1l of milk would be below therapeutic doses. However, breast-feeding is not recommended because of potential quinidine accumulation in the immature newborn liver. /Quinidine/
International Programme on Chemical Safety; Poisons Information Monograph: Quinidine (PIM 463) (1990) Available from, as of April 7, 2009: https://www.inchem.org/pages/pims.html

12.1.2 Hepatotoxicity

Chronic therapy with quinidine is associated with a low rate of serum enzyme elevations, which are usually mild, asymptomatic and self limited even without alteration in dose. In addition, there have been many reports of acute hypersensitivity reactions to quinidine that include hepatic involvement. The reactions usually arise after 1 to 2 weeks of therapy, but can appear within 24 hours of restarting quinidine or with rechallenge. The clinical features are marked by fatigue, nausea, vomiting, diffuse muscle aches, arthralgias and high fever. Blood testing at an early stage shows increases in serum aminotransferase and alkaline phosphatase levels as well as mild jaundice, which can deepen for a few days even after stopping quinidine. The pattern of serum enzymes elevations is typically cholestatic or mixed. Rash is uncommon and eosinophilia is not typical, despite the presence of other signs of hypersensitivity (fever, arthralgias). Autoantibodies are not typically found. Liver biopsies usually show mild injury and small epithelioid granulomas, as are often found in many organs during systemic hypersensitivity reactions. A similar clinical signature of liver injury occurs with quinine, an optical isomer of quinidine that is used predominantly as an antimalarial agent. In recent years, there have been few reports of liver injury attributed to quinidine, probably because it is now rarely used.

Likelihood score: A (well established cause of clinically apparent liver injury).

12.1.3 Drug Induced Liver Injury

Compound
quinidine
DILI Annotation
Less-DILI-Concern
Severity Grade
3
Label Section
Adverse reactions
References

M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007

M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

12.1.4 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Limited information indicates that maternal doses of quinidine up to 1.8 grams daily produce low levels in milk and would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. Exclusively breastfed infants should be carefully monitored if this drug is used during lactation, possibly including measurement of serum levels to rule out toxicity if there is a concern.

◉ Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

◉ Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

12.1.5 Adverse Effects

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.

Skin Sensitizer - An agent that can induce an allergic reaction in the skin.

12.1.6 Acute Effects

12.1.7 Interactions

The combination of propranolol and quinidine resulted in increased beta-blockade measured by reduction in exercise heart rate and prolongation of the QTc and PR intervals ... quinidine stereoselectively inhibits the metabolism of propranolol through inhibition of the debrisoquin isozyme. The increased concentration of propranolol produced by quinidine results in increased beta-blockade.
Zhou HH et al; Clin Pharmacol Ther 47 (6): 686-93 (1990)
Ethacrynic acid and furosemide /diuretics/ increase lipid solubility and tubular reabsorption of quinidine and thus prolong its therapeutic effects/ ...but will not alkalinize urine... .
Evaluations of Drug Interactions. 2nd ed. and supplements. Washington, DC: American Pharmaceutical Assn., 1976, 1978., p. 355
Quinidine may potentiate the effects of both nondepolarizing and depolarizing skeletal muscle relaxants such as pancuronium bromide, succinylcholine chloride, and tubocurarine chloride. Neostigmine methylsulfate does not appear to reverse these effects.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1569
Quinidine should be used with caution, if at all, in patients with myasthenia gravis and the dose of anticholinesterase drugs such as neostigmine and pyridostigmine may have to be increased. Since quinidine antagonizes the effect of vagal excitation on the atria and AV node, the administration of cholinergic drugs or any other procedures to enhance vagal activity may fail to terminate paroxysmal supraventricular tachycardia in patients receiving quinidine. The anticholinergic effects of quinidine may be additive with those of anticholinergic drugs.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1569
For more Interactions (Complete) data for QUINIDINE (24 total), please visit the HSDB record page.
THE ADMIN OF QUINIDINE RESULTS IN AN INCREASE IN THE PLASMA CONCN OF THE GLYCOSIDE IN OVER 90% OF DIGITALIZED PATIENTS. THE DEGREE OF CHANGE IS PROPORTIONAL TO THE DOSE OF QUINIDINE; THE AVERAGE CHANGE IS ABOUT TWO-FOLD. ... THE INITIAL EFFECT OF QUINIDINE MAY BE DUE TO THE DISPLACEMENT OF DIGOXIN FROM BINDING SITES IN TISSUES. /QUINIDINE/
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 836
DRUGS ... SUCH AS PHENOBARBITAL OR PHENYTOIN ... MAY SIGNIFICANTLY SHORTEN DURATION OF ACTION OF QUINIDINE BY INCR RATE OF ELIMINATION. ... NITROGLYCERIN CAN CAUSE SEVERE POSTURAL HYPOTENSION IN PATIENTS WHO ARE TAKING QUINIDINE. /QUINIDINE/
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 857
QUINIDINE IS WEAK BASE EXCRETED ... BY KIDNEY & ITS BIOLOGICAL HALF-LIFE MAY BE PROLONGED ... IF PH OF URINE IS INCREASED. ... CARBONIC ANHYDRASE INHIBITORS, SODIUM BICARBONATE, & THIAZIDE DIURETICS, ALL OF WHICH INCR URINARY PH MAY SERVE TO INCR LIPID SOLUBILITY & TUBULAR REABSORPTION OF QUINIDINE & THUS PROLONG ITS THERAPEUTIC EFFECT. /QUINIDINE/
Evaluations of Drug Interactions. 2nd ed. and supplements. Washington, DC: American Pharmaceutical Assn., 1976, 1978., p. 355
QUINIDINE (300 MG), SLOWLY ADMIN IV, CAUSED RETURN OF PARALYSIS INDUCED BY SUCCINYLCHOLINE (40 MG IV). QUINIDINE MAY ENHANCE OR CAUSE A RECURRENCE OF NEUROMUSCULAR EFFECTS OF TUBOCURARINE. /QUINIDINE/
Evaluations of Drug Interactions. 2nd ed. and supplements. Washington, DC: American Pharmaceutical Assn., 1976, 1978., p. 260
For more Interactions (Complete) data for QUINIDINE SULFATE (30 total), please visit the HSDB record page.

12.1.8 Antidote and Emergency Treatment

Decontamination. 1. Prehospital. Administer activated charcoal if available. Do not induce vomiting because of the risk of abrupt onset of seizures and coma. 2. Hospital. Administer activated charcoal. Consider gastric lavage for large ingestions. /Quinidine and other type Ia antiarrhythmic drugs/
Olson, K.R. (ed.) Poisoning & Drug Overdose. 3rd edition. Lange Medical Books/McGraw-Hill, New York, NY. 1999., p. 278
General management is similar to that described for other drug overdoses. Because of potentially slow absorption, emesis or lavage and charcoal should be used even many hours after ingestion. Similarly, evaluation of intoxicated patients must continue until it is clear that the patient is stable and absorption is complete. Seizures should be treated with intravenous administration of diazepam initially and then phenytoin. /Quinidine/
Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990., p. 1367
Hypotension may be due to decreased systemic vascular resistance (particularly with quinidine) or to decreased cardiac output secondary to myocardial depression. The latter is most significant in cases of severe intoxication, in which cardiogenic shock may be a cause of death. Cautious use of fluids is usually effective in managing hypotension due to vasodilating or adrenergic blocking agents /including quinidine/. If blood pressure does not respond to fluids, vasoconstrictor drugs such as norepinephrine or dopamine should be used. ... Differentiating hypotension caused by vasodilation from that caused by myocardial depression and selecting appropriate therapy require measurement of cardiac output. Thus placement of a pulmonary arterial catheter is desirable. If cardiac output is low and cardiac filling pressure is also low, more fluids are necessary. If cardiac output is low despite adequate filling pressures, inotropic agents should be administered. Animal studies have shown isoproterenol to be most effective in reversing disopyramide-induced myocardial depression. Dobutamine should also be considered. If cardiac output is adequate but vascular resistance is low, vasopressors should be administered. ... In severe cases of quinidine poisoning with low-output shock due to myocardial depression, inotropic drugs may not improve contractility. Yet, in contrast to the situation of cardiogenic shock due to myocardial infarction, if the patient can be supported for several hours until the intoxicating drug can be eliminated, myocardial function will return to normal. Thus, drug-induced cardiogenic shock is an ideal situation for use of extracorporeal circulatory assistance techniques. /Quinidine/
Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990., p. 1369
Hemodialysis and hemoperfusion remove relatively little quinidine ... because of extensive tissue distribution of the drug. But when the usual routes of drug elimination are depressed or absent, such as when renal or hepatic failure complicates procainamide or quinidine overdose, respectively, or when extracorporeal circulation is used to support a failing circulation, ... hemoperfusion should be strongly considered because, even though not terribly effective it may offer the only route of drug elimination. /Quinidine/
Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990., p. 1369
Serious poisoning may present early with cardiovascular collapse. Therefore iv lines, oxygen, and cardiac monitoring are first priorities. Convulsions are often responsive to diazepam. Failure to respond to the usual anticonvulsant drugs is an indication to check serum electrolytes (particularly calcium) and glucose levels. Respiratory distress may result from either respiratory depression, aspiration pneumonia, or the development of the adult respiratory distress syndrome. In patients with underlying cardiovascular disease, pulmonary edema may result from depressed myocardial contractility. The usual measures of emesis/lavage, activated charcoal, and cathartics within the first several hours (longer if sustained-release preparations are ingested) are indicated. Repeated doses of activated charcoal (every 3 to 4 hr) may enhance the elimination of quinidine trapped in the acid media of the stomach. Although renal excretion of unmetabolized quinidine increases in acid urine, the usefulness of acid diuresis has not been clinically evaluated. Dialysis does not remove a clinically significant amount of quinidine, because of the high degree of protein binding, and should be used only in the presence of renal failure. Hemoperfusion may be useful if hepatic failure reduces metabolism. Glucagon has a positive inotropic effect in dogs, but its clinical efficacy has not been evaluated. Bretylium antagonizes quinidine-induced toxic effects on ventricular fibers, but it may enhance quinidine-induced reduction in atrioventricular conduction.Hypotension should be treated initially with fluids, pneumatic trousers, and, if required, vasopressors. Both isoproterenol and norepinephrine have been used successfully, and a resistant case has responded to the placement of an intra-aortic balloon pump. Persistent hypotension should be managed with a pulmonary catheter and arterial lines in coronary care unit. Treat ventricular dysrhythmias with class IB drugs (lidocaine, phenytoin), and avoid class IA drugs (procainamide, isopyramide). Bretylium should be used with caution because of synergistic atrioventricular nodal suppression. When atypical ventricular tachycardia presents, the goal is to reduce the QT interval. Isoproterenol infusion, 2 to 8 ug/min, may be effective, but usually overdrive pacing (120 to 140/min) is necessary. Lidocaine and procainamide are not effective and may be deleterious. Be sure to correct electrolyte imbalances (especially hypokalemia). /Quinidine/
Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 182
For more Antidote and Emergency Treatment (Complete) data for QUINIDINE SULFATE (8 total), please visit the HSDB record page.

12.1.9 Human Toxicity Excerpts

/SIGNS AND SYMPTOMS/ The /cardiac/ conduction velocity decreases progressively as drug concentrations rise, as reflected by increases in the PR interval, QRS duration and QT interval. High plasma quinidine levels cause high-grade atrioventricular block, bundle-branch block, and asystole resembling that of hyperkalemia.
Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 511
/SIGNS AND SYMPTOMS/ Quinidine is a antiarrhythmic drug in the class 1A category. This drug has a low toxic to therapeutic ratio, and its use is associated with a number of serious adverse effects during long term therapy and life threatening sequelae following acute overdose. ... Severe intoxication with the class 1A agents may result from acute accidental or intentional overdose, or from accumulation of the drugs during long term therapy. Acute overdose can result in severe disturbances of cardiac conduction and hypotension, frequently accompanied by central nervous system toxicity.
Kim SY, Benowitz NL; Drug Saf 5 (6): 393-420 (1990)
/CASE REPORTS/ A patient is described with quinidine induced acute lymphadenopathy syndrome proven by rechallenge of the drug. Serum markers for systemic lupus were negative.
Lau CP et al; Postgrad Med J 66 (775): 406-7 (1990)
/CASE REPORTS/ Pulmonary edema developed after a suicidal 8 gram quinidine ingestion with normal pulmonary capillary wedge pressures.
Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 511
/CASE REPORTS/ Fever is a well-known side effect of quinidine therapy, but an elevated white blood cell count is considered unusual. Two patients are described who had leukocytosis or a marked left shift in the white blood cell count (or both) in association with quinidine fever. Neither patient had evidence of infection. In each of these patients, the temperature and white blood cell count returned to normal within two days after quinidine was discontinued. Although infection should always be considered in a patient with fever, leukocytosis, and a left shift, these may also appear in association with quinidine therapy.
Bedell SE et al; Am J Med 77 (2): 345-6 (1984)
... COMPLICATION OF QUINIDINE WHEN DRUG IS USED TO TREAT ATRIAL FIBRILLATION IS ... PARADOXICAL INCR IN VENTRICULAR RATE. ... QUINIDINE CAUSES SUBSTANTIAL DECR IN THE ATRIAL RATE. IF THE ATRIAL RATE DECR SUFFICIENTLY, VENTRICULAR RATE MAY ABRUPTLY RISE ... . /QUINIDINE/
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 855
QUINIDINE CAN CAUSE SIGNIFICANT HYPOTENSION, PARTICULARLY WHEN GIVEN IV. ... HEMODYNAMIC STUDIES ... REVEALED THAT HYPOTENSION DUE TO QUINIDINE IS CAUSED BY VASODILATATION WITHOUT SIGNIFICANT DECREASE IN CARDIAC OUTPUT. /QUINIDINE/
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 855
... QUINIDINE CAN CAUSE CINCHONISM. SYMPTOMS ... INCL TINNITUS, LOSS OF HEARING, SLIGHT BLURRING OF VISION, & GI UPSET. IF TOXICITY IS SEVERE, HEADACHE, DIPLOPIA, PHOTOPHOBIA, & ALTERED COLOR PERCEPTION ... CONFUSION, DELIRIUM, & PSYCHOSIS. SKIN ... HOT AND FLUSHED, NAUSEA, VOMITING, DIARRHEA, & ABDOMINAL PAIN. /QUINIDINE/
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 855
RARELY, QUINIDINE CAUSES ANAPHYLACTIC REACTIONS, WHICH REQUIRE USUAL EMERGENCY MEASURES. THROMBOCYTOPENIA IS AN UNCOMMON BUT POTENTIALLY LETHAL OUTCOME OF TREATMENT WITH QUINIDINE. ... ASTHMA-LIKE RESPIRATORY DIFFICULTY OR VASCULAR COLLAPSE CAN OCCUR AS RESULT OF HYPERSENSITIVITY. /QUINIDINE/
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 856
For more Human Toxicity Excerpts (Complete) data for QUINIDINE SULFATE (29 total), please visit the HSDB record page.

12.1.10 Non-Human Toxicity Excerpts

Amphetamine is metabolizedby cytochrome p450 to p-hydroxyamphetamine and phenylacetone in mammalian species. Cytochrome p450 metabolism is affected by genetic polymorphisms and by xenobiotic interactions in an isozyme specific fashion. Little is known concerning the isozyme selectivity of amphetamine metabolism. Quinidine selectively inhibits the debrisoquine specific isozyme (p450db) which displays genetic polymorphism in ... rats. The effect of quinidine on themetabolism of amphetamine to p-hydroxyamphetamine in vivo is reported. At 0 hr male Lewis rats received (orally): no treatment, 80 mg quinidine/kg in 50% ethanol, or 50% ethanol, followed at 2 hr by 15 mg d-amphetamine sulfate/kg (orally). Urine specimens were collected and pooled at 0, 24, and 48 hr. Amphetamine and p-hydroxyamphetamine concentrations were determined using a new GC/MS method for simultaneous quantitation. The ethanol vehicle control (50% ethanol) had no significant effect on amphetamine metabolism. Quinidine pretreatment (80 mg quinidine/kg in 50% ethanol) resulted in a significant decrease in the excretion of p-hydroxyamphetamine at 24 and 48 hr to 7.2 and 24.1% of the vehicle control levels, respectively, accompanied by a significant increase in amphetamine excretion between 24 and 48 hr to 542% of the control. These data show that quinidine inhibits in vivo metabolism of amphetamine in rats and suggest that amphetamine metabolism may, in part, be mediated by an isozyme of cytochome p450 which displays genetic polymorphism. The inhibition of amphetamine metabolism results in an increased ratio of parent drug to metabolite concentration (metabolic ratio) in the urine, which mimics the effect of genetic polymorphisms. /Quinidine/
Moody DE et al; J Anal Toxicol 14 (5): 311-7 (1990)
Thrombocytopenia due to drug dependent antibodies most frequently occurs with quinine/quinidine and with heparin. Considerable evidence has accumulated about the mechanism of action of quinine/quinidine induced antibodies but less is known about the effect of heparin. Although there is controversy, it is likely that the action of quinine/quinidine induced antibodies follows a loose association between drug and platelet with antibodies acting independently of the Fc receptor. There is strong evidence that the complex of glycoprotein Ib and glycoprotein IX, absent in the Bernard-Soulier syndrome, provides the binding site for quinine/quinidine dependent antibodies. It also appears that the two glycoproteins must be present in complex form for antibody binding to occur. There is some heterogeneity of quinine/quinidine dependent antibodies since there are reports of a proportion of patient antibodies reacting with other membrane determinants or acting independently of the drug. /Quinidine/
Berndt MC, Castaldi PA; Blood Rev 1 (2): 111-8 (1987)

12.1.11 Non-Human Toxicity Values

LD50 Rat iv 30.0 mg/kg
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1443
LD50 Rat i.v. 23 mg/kg
DHHS/National Toxicology Program; Chemical Health & Safety Data File. Available from: https://ntp-db.niehs.nih.gov/cgi/iH_Indexes/Chem_H&S/iH_Chem_H&S_Frames.html on quinidine; 56-54-2 as January 17, 2003
LD50 Rat oral 263 mg/kg
DHHS/National Toxicology Program; Chemical Health & Safety Data File. Available from: https://ntp-db.niehs.nih.gov/cgi/iH_Indexes/Chem_H&S/iH_Chem_H&S_Frames.html on quinidine; 56-54-2 as January 17, 2003
LD50 Mouse i.p. 170 mg/kg
DHHS/National Toxicology Program; Chemical Health & Safety Data File. Available from: https://ntp-db.niehs.nih.gov/cgi/iH_Indexes/Chem_H&S/iH_Chem_H&S_Frames.html on quinidine; 56-54-2 as January 17, 2003
For more Non-Human Toxicity Values (Complete) data for QUINIDINE (7 total), please visit the HSDB record page.

12.1.12 Populations at Special Risk

Quinidine should be used with extreme caution, if at all, in patients with incomplete atrioventricular nodal block, since complete heart block and asystole may result. IM or iv administration of quinidine is especially hazardous in the presence of atrioventricular block, in the absence of atrial activity, and the patients with extensive myocardial injury. Hypokalemia, hypoxia, and disorders of acid base balance must be eliminated as potentiating factors in patients who require large doses of antiarrhythmic agents to control ventricular arrhythmias.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 995
Quinidine should be used with extreme caution in patients with cardiac glycoside intoxication, since cardiac glycoside intoxication may cause serious impairment of cardiac conduction and produce arrhythmias which may contraindicate use of quinidine. Conversely, quinidine may cause unpredictable, abnormal rhythms and decreased contractility in the presence of cardiac glycoside intoxication.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 995
Since quinidine-induced decreases in cardiac contractility and blood pressure may aggravate congestive heart failure or preexisting hypotension, the drug should be used cautiously, if at all, in patients with these conditions. If hypotension or congestive heart failure is caused or aggravated by an arrhythmia treatable with quinidine, the drug may be useful, but the potential risks and benefits must be considered.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 995
Quinidine should be used with caution in patients with preexisting asthma, muscle weakness, or infection with fever, since hypersensitivity reactions to the drug may be masked. The drug should also be used with caution in patients with hepatic and/or renal (particularly if renal tubular acidosis is present) insufficiency, since systemic accumulation of quinidine potentially may result.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 995
INDIVIDUALS WITH THE LONG Q-T SYNDROME OR THOSE WHO RESPOND TO LOW CONCENTRATIONS OF QUINIDINE WITH MARKED LENGTHENING OF THE Q-T INTERVAL APPEAR TO BE PARTICULARLY AT RISK /OF SYNCOPE OR SUDDEN DEATH/ AND SHOULD NOT BE TREATED WITH THIS DRUG. /QUINIDINE/
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 853

12.1.13 Protein Binding

From 6.5 to 16.2 µmol/L, 80 to 88% of quinidine is bound to plasma proteins, mainly α1-acid glycoprotein and albumin. This fraction is lower in pregnant women, and it may be as low as 50 to 70% in infants and neonates.

12.2 Ecological Information

12.2.1 Natural Pollution Sources

Obtained from various species of Cinchona and their hybrids and from Remijia pedunculata Fluckiger (Fam Rubiaceae).
GENNARO. REMINGTON'S PHARM SCI 17TH ED 1985 p.860
Quinidine is a stereoisomer of quinine and occurs in cinchona bark in amounts ranging from 0.3 to over 1%, although in some barks it may be practically absent.
GENNARO. REMINGTON'S PHARM SCI 17TH ED p.860 (1985)

12.2.2 Artificial Pollution Sources

Found in quinidine sulfate mother liquors. /Quinidine sulfate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1443

12.2.3 Milk Concentrations

Since quinidine is distributed into milk, the drug should be used with extreme caution in nursing women.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 1569

13 Associated Disorders and Diseases

Associated Occupational Diseases with Exposure to the Compound
Contact dermatitis, allergic [Category: Skin Disease]
Disease
Colorectal cancer
References

PubMed: 7482520, 22148915, 19006102, 23940645, 24424155, 20156336, 19678709, 25105552, 21773981, 25037050, 27015276, 27107423, 27275383, 28587349

Silke Matysik, Caroline Ivanne Le Roy, Gerhard Liebisch, Sandrine Paule Claus. Metabolomics of fecal samples: A practical consideration. Trends in Food Science & Technology. Vol. 57, Part B, Nov. 2016, p.244-255: http://www.sciencedirect.com/science/article/pii/S0924224416301984

14 Literature

14.1 Consolidated References

14.2 NLM Curated PubMed Citations

14.3 Springer Nature References

14.4 Thieme References

14.5 Wiley References

14.6 Nature Journal References

14.7 Chemical Co-Occurrences in Literature

14.8 Chemical-Gene Co-Occurrences in Literature

14.9 Chemical-Disease Co-Occurrences in Literature

15 Patents

15.1 Depositor-Supplied Patent Identifiers

15.2 WIPO PATENTSCOPE

15.3 FDA Orange Book Patents

15.4 Chemical Co-Occurrences in Patents

15.5 Chemical-Disease Co-Occurrences in Patents

15.6 Chemical-Gene Co-Occurrences in Patents

16 Interactions and Pathways

16.1 Protein Bound 3D Structures

16.1.1 Ligands from Protein Bound 3D Structures

PDBe Ligand Code
PDBe Structure Code
PDBe Conformer

16.2 Chemical-Target Interactions

16.3 Drug-Drug Interactions

16.4 Drug-Food Interactions

  • Exercise caution with grapefruit products. Grapefruit may delay the absorption of quinidine, and inhibit its metabolism through CYP3A4.
  • Exercise caution with St. John's Wort.
  • Take separate from antacids. Antacids may reduce the absorption of quinidine.
  • Take with or without food. Taking quinidine with food may slow its absorption.

16.5 Pathways

17 Biological Test Results

17.1 BioAssay Results

18 Taxonomy

The LOTUS Initiative for Open Natural Products Research: frozen dataset union wikidata (with metadata) | DOI:10.5281/zenodo.5794106

19 Classification

19.1 MeSH Tree

19.2 NCI Thesaurus Tree

19.3 ChEBI Ontology

19.4 WHO ATC Classification System

19.5 FDA Pharm Classes

19.6 ChemIDplus

19.7 CAMEO Chemicals

19.8 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

19.9 ChEMBL Target Tree

19.10 UN GHS Classification

19.11 NORMAN Suspect List Exchange Classification

19.12 CCSBase Classification

19.13 EPA DSSTox Classification

19.14 The Natural Products Atlas Classification

19.15 EPA TSCA and CDR Classification

19.16 LOTUS Tree

19.17 FDA Drug Type and Pharmacologic Classification

19.18 MolGenie Organic Chemistry Ontology

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  37. MassBank of North America (MoNA)
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  38. KEGG
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  39. Natural Product Activity and Species Source (NPASS)
  40. The Natural Products Atlas
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    https://www.npatlas.org/terms
    The Natural Products Atlas Classification
    https://www.npatlas.org/
  41. MassBank Europe
  42. Metabolomics Workbench
  43. Nature Chemistry
  44. NIPH Clinical Trials Search of Japan
  45. NLM RxNorm Terminology
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    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  46. PharmGKB
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  47. Pharos
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  48. Protein Data Bank in Europe (PDBe)
  49. RCSB Protein Data Bank (RCSB PDB)
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  50. SpectraBase
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  54. WHO Anatomical Therapeutic Chemical (ATC) Classification
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  55. Wikidata
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  58. Medical Subject Headings (MeSH)
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    Adrenergic alpha-Antagonists
    https://www.ncbi.nlm.nih.gov/mesh/68000317
    Cytochrome P-450 CYP2D6 Inhibitors
    https://www.ncbi.nlm.nih.gov/mesh/68065690
    Voltage-Gated Sodium Channel Blockers
    https://www.ncbi.nlm.nih.gov/mesh/68061567
  59. PubChem
  60. GHS Classification (UNECE)
  61. MolGenie
    MolGenie Organic Chemistry Ontology
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  62. PATENTSCOPE (WIPO)
  63. NCBI
CONTENTS