vin cristine wikipedia

8/13/2019 Vin Cristine wikipedia

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Vincristine

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Vincristine

Systematic (IUPAC) name

(3aR,3a1R,R,!",!aR,1#$R%&methyl &aceto'y&3a&ethyl&&((!",)","%&!&ethyl&!&hydro'y&&(metho'ycar$onyl%&*,,!,+,),,,1#&octahydro&1-&3,)&

methano.1/a0acycloundecino.!,&$/indol&&yl%&+&formyl&!&hydro'y&&

metho'y&3a,3a1,,!,!a,+,11,1*&octahydro&1-&indoli0ino.,1&cd/car$a0ole&!&car$o'ylate

Clinical data

AHFS/Drugs.com monograph

MedlinePlus a+***

Pregnancy cat. (2% ("%

egal status 4rescription only

!outes "#clusi$elyintravenous

P%armaco&inetic data

'ioa$ailaility n5a

Protein inding 6)!7

Metaolism -epatic

Hal*lie 1 to 1!! hours

"#cretion 8ostly $iliary, 1#7 in urine

Identiiers

CAS numer !)&**&)

A+C code 9#1 2#*

PuC%em ; !)

Drug'an& 8


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Mol. mass *?! g5mol

"8;9>".sho@/

;nh;.sho@/

(1%at is t%is2) ($eriy)

Vincristine($rand name, Ancovin%, formally kno@n as leurocristine, sometimesa$$reviated BVRB, is a vinca alkaloidfrom the Catharanthus roseus(8adagascarperi@inkle%, formerly Vinca roseaand hence its name? ;t is a mitotic inhi$itor, and is used

in cancer chemotherapy? Vincristine is created $y the coupling of indole alkaloids

vindoline and catharanthine in the vinca plant?.1/

Contents

1 8echanism

* ses

3 "ide&effects -istory

! "uppliers

+ "ee also

) References

>'ternal links

Mec%anism

Cu$ulinis a structural protein thatpolymeri0esto microtu$ules?Che cell cytoskeletonand mitotic spindle, among other things, are made of microtu$ules? Vincristine$inds to

tu$ulin dimers, inhi$iting assem$ly of microtu$ule structures? isruption of the

microtu$ules arrests mitosisin metaphase? Cherefore, thevincaalkaloidsaffect all

rapidly dividing cell types including cancer cells, $ut also those of intestinal epitheliumand$one marro@?

Uses

Vincristine is delivered viaintravenousinfusionfor use in various types of chemotherapy

regimens? ;ts main uses are in non&-odgkinDslymphomaas part of the chemotherapy

regimen -A4,-odgkinDs lymphomaas part of 8A44, A44, 2A44, or the lesspopular "tanford Vchemotherapy regimen, in acute lympho$lastic leukemia, and in

treatment for nephro$lastoma(Wilms tumor, a kidney tumor most common in youngchildren%? ;t is also used to induce remission in A@ith e'amethasone and 9&

2sparaginase? Vincristine is occasionally used as an immunosuppressant,for e'ample, in

treating throm$otic throm$ocytopenic purpura(CC4% or chronic idiopathicthrom$ocytopenic purpura(;C4%? ;t is used in com$ination @ithprednisoneto treat

childhood leukemia?
http://en.wikipedia.org/wiki/Molecular_masshttp://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specificationhttp://en.wikipedia.org/wiki/International_Chemical_Identifierhttp://en.wikipedia.org/wiki/Wikipedia:WikiProject_Chemicals/Chembox_validationhttp://en.wikipedia.org/w/index.php?title=Special:ComparePages&rev1=461759697&page2=Vincristinehttp://en.wikipedia.org/wiki/Vinca_alkaloidhttp://en.wikipedia.org/wiki/Catharanthus_roseushttp://en.wikipedia.org/wiki/Mitotic_inhibitorhttp://en.wikipedia.org/wiki/Chemotherapyhttp://en.wikipedia.org/wiki/Vincristine#cite_note-0http://en.wikipedia.org/wiki/Vincristine#Mechanismhttp://en.wikipedia.org/wiki/Vincristine#Useshttp://en.wikipedia.org/wiki/Vincristine#Side-effectshttp://en.wikipedia.org/wiki/Vincristine#Historyhttp://en.wikipedia.org/wiki/Vincristine#Suppliershttp://en.wikipedia.org/wiki/Vincristine#See_alsohttp://en.wikipedia.org/wiki/Vincristine#Referenceshttp://en.wikipedia.org/wiki/Vincristine#External_linkshttp://en.wikipedia.org/wiki/Tubulinhttp://en.wikipedia.org/wiki/Polymerhttp://en.wikipedia.org/wiki/Polymerhttp://en.wikipedia.org/wiki/Microtubulehttp://en.wikipedia.org/wiki/Microtubulehttp://en.wikipedia.org/wiki/Cytoskeletonhttp://en.wikipedia.org/wiki/Mitotic_spindlehttp://en.wikipedia.org/wiki/Mitosishttp://en.wikipedia.org/wiki/Metaphasehttp://en.wikipedia.org/wiki/Vincahttp://en.wikipedia.org/wiki/Vincahttp://en.wikipedia.org/wiki/Alkaloidshttp://en.wikipedia.org/wiki/Alkaloidshttp://en.wikipedia.org/wiki/Epitheliumhttp://en.wikipedia.org/wiki/Bone_marrowhttp://en.wikipedia.org/wiki/Intravenoushttp://en.wikipedia.org/wiki/Intravenoushttp://en.wikipedia.org/wiki/Route_of_administrationhttp://en.wikipedia.org/wiki/Route_of_administrationhttp://en.wikipedia.org/wiki/Chemotherapy_regimenshttp://en.wikipedia.org/wiki/Chemotherapy_regimenshttp://en.wikipedia.org/wiki/Lymphomahttp://en.wikipedia.org/wiki/Lymphomahttp://en.wikipedia.org/wiki/CHOPhttp://en.wikipedia.org/wiki/CHOPhttp://en.wikipedia.org/wiki/Hodgkin's_lymphomahttp://en.wikipedia.org/wiki/Stanford_Vhttp://en.wikipedia.org/wiki/Acute_lymphoblastic_leukemiahttp://en.wikipedia.org/wiki/Nephroblastomahttp://en.wikipedia.org/wiki/Asparaginasehttp://en.wikipedia.org/wiki/Immunosuppressanthttp://en.wikipedia.org/wiki/Immunosuppressanthttp://en.wikipedia.org/wiki/Thrombotic_thrombocytopenic_purpurahttp://en.wikipedia.org/wiki/Idiopathic_thrombocytopenic_purpurahttp://en.wikipedia.org/wiki/Idiopathic_thrombocytopenic_purpurahttp://en.wikipedia.org/wiki/Prednisonehttp://en.wikipedia.org/wiki/Prednisonehttp://en.wikipedia.org/wiki/Molecular_masshttp://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specificationhttp://en.wikipedia.org/wiki/International_Chemical_Identifierhttp://en.wikipedia.org/wiki/Wikipedia:WikiProject_Chemicals/Chembox_validationhttp://en.wikipedia.org/w/index.php?title=Special:ComparePages&rev1=461759697&page2=Vincristinehttp://en.wikipedia.org/wiki/Vinca_alkaloidhttp://en.wikipedia.org/wiki/Catharanthus_roseushttp://en.wikipedia.org/wiki/Mitotic_inhibitorhttp://en.wikipedia.org/wiki/Chemotherapyhttp://en.wikipedia.org/wiki/Vincristine#cite_note-0http://en.wikipedia.org/wiki/Vincristine#Mechanismhttp://en.wikipedia.org/wiki/Vincristine#Useshttp://en.wikipedia.org/wiki/Vincristine#Side-effectshttp://en.wikipedia.org/wiki/Vincristine#Historyhttp://en.wikipedia.org/wiki/Vincristine#Suppliershttp://en.wikipedia.org/wiki/Vincristine#See_alsohttp://en.wikipedia.org/wiki/Vincristine#Referenceshttp://en.wikipedia.org/wiki/Vincristine#External_linkshttp://en.wikipedia.org/wiki/Tubulinhttp://en.wikipedia.org/wiki/Polymerhttp://en.wikipedia.org/wiki/Microtubulehttp://en.wikipedia.org/wiki/Cytoskeletonhttp://en.wikipedia.org/wiki/Mitotic_spindlehttp://en.wikipedia.org/wiki/Mitosishttp://en.wikipedia.org/wiki/Metaphasehttp://en.wikipedia.org/wiki/Vincahttp://en.wikipedia.org/wiki/Alkaloidshttp://en.wikipedia.org/wiki/Epitheliumhttp://en.wikipedia.org/wiki/Bone_marrowhttp://en.wikipedia.org/wiki/Intravenoushttp://en.wikipedia.org/wiki/Route_of_administrationhttp://en.wikipedia.org/wiki/Chemotherapy_regimenshttp://en.wikipedia.org/wiki/Chemotherapy_regimenshttp://en.wikipedia.org/wiki/Lymphomahttp://en.wikipedia.org/wiki/CHOPhttp://en.wikipedia.org/wiki/Hodgkin's_lymphomahttp://en.wikipedia.org/wiki/Stanford_Vhttp://en.wikipedia.org/wiki/Acute_lymphoblastic_leukemiahttp://en.wikipedia.org/wiki/Nephroblastomahttp://en.wikipedia.org/wiki/Asparaginasehttp://en.wikipedia.org/wiki/Immunosuppressanthttp://en.wikipedia.org/wiki/Thrombotic_thrombocytopenic_purpurahttp://en.wikipedia.org/wiki/Idiopathic_thrombocytopenic_purpurahttp://en.wikipedia.org/wiki/Idiopathic_thrombocytopenic_purpurahttp://en.wikipedia.org/wiki/Prednisone


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Side*eects

Che main side&effects of vincristine areperipheral neuropathy, hyponatremia,

constipation, and hair loss?

4eripheral neuropathy can $e severe, and hence a reason to avoid, reduce, or stop the useof vincristine? Ane of the first symptoms of peripheral neuropathy isfoot drop: 2 person

@ith a family history of foot drop and5or harcot&8arie&Cooth disease(8C% may

$enefit from genetic testing for 8C $efore taking vincristine?.*/

2ccidental inEection of vinca alkaloids into the spinal canal ( intrathecaladministration% is

highly dangerous, @ith a mortality rate approaching 1## percent? Che medical literature

documents cases of ascendingparalysisdue to massive encephalopathyand spinal nervedemyelination, accompanied $y intracta$le pain, almost uniformly leading to death a

handful of survivors @ere left @ith devastating neurological damage @ith no hope of

recovery? Rescue treatments consist of @ashout of thecere$rospinal fluidand

administration of protective medications?.3/2 significant series of inadvertent intrathecalvincristine administration occurred in hinain *##) @hen $atches of cytara$ineand

methotre'ate($oth often used intrathecally% manufactured $y the company "hanghai

-ualian @ere found to $e contaminated @ith vincristine?./

History

-aving $een used as a folk remedy for centuries, studies in the 1!#s revealed thatC.

roseuscontained )# alkaloids, many of @hich are $iologically active? While initial

studies for its use in dia$etes mellitus@ere disappointing, the discovery that it caused

myelosuppression(decreased activity of the $one marro@% led to its study in mice @ithleukemia, @hose lifespan @as prolonged $y the use of a vinca preparation? Creatment of

the ground plant @ith "kelly&< defatting agent and an acid $en0ene e'tract led to afraction termed Bfraction 2B? Chis fraction @as further treated @ith aluminium o'ide,

chromatography, trichloromethane, $en0&dichloromethane, and separation $y p- to yield

vincristine?.!/

Vincristine @as approved $y the nited "tatesFood and rug 2dministration(F2% inJuly 1+3 as Ancovin? Che drug @as initially discovered $y a team led $y r? J?G?

2rmstrong, then marketed $y >li 9illy and ompany?

Su,,liers

Chree generic drug makers supply vincristine in the nited "tates & 244, 8ayne, and"icor (Ceva%?
http://en.wikipedia.org/wiki/Cancer_pain#Chemotherapy-induced_peripheral_neuropathyhttp://en.wikipedia.org/wiki/Hyponatremiahttp://en.wikipedia.org/wiki/Constipationhttp://en.wikipedia.org/wiki/Alopeciahttp://en.wikipedia.org/wiki/Foot_drophttp://en.wikipedia.org/wiki/Foot_drophttp://en.wikipedia.org/wiki/Charcot-Marie-Tooth_diseasehttp://en.wikipedia.org/wiki/Charcot-Marie-Tooth_diseasehttp://en.wikipedia.org/wiki/Vincristine#cite_note-1http://en.wikipedia.org/wiki/Intrathecalhttp://en.wikipedia.org/wiki/Intrathecalhttp://en.wikipedia.org/wiki/Paralysishttp://en.wikipedia.org/wiki/Encephalopathyhttp://en.wikipedia.org/wiki/Demyelinationhttp://en.wikipedia.org/wiki/Cerebrospinal_fluidhttp://en.wikipedia.org/wiki/Cerebrospinal_fluidhttp://en.wikipedia.org/wiki/Vincristine#cite_note-2http://en.wikipedia.org/wiki/Chinahttp://en.wikipedia.org/wiki/Cytarabinehttp://en.wikipedia.org/wiki/Cytarabinehttp://en.wikipedia.org/wiki/Methotrexatehttp://en.wikipedia.org/wiki/Vincristine#cite_note-3http://en.wikipedia.org/wiki/Vincristine#cite_note-3http://en.wikipedia.org/wiki/Vinca_roseahttp://en.wikipedia.org/wiki/Vinca_roseahttp://en.wikipedia.org/wiki/Vinca_roseahttp://en.wikipedia.org/wiki/Diabetes_mellitushttp://en.wikipedia.org/wiki/Myelosuppressionhttp://en.wikipedia.org/wiki/Leukemiahttp://en.wikipedia.org/wiki/Aluminium_oxidehttp://en.wikipedia.org/wiki/Chromatographyhttp://en.wikipedia.org/wiki/Chloroformhttp://en.wikipedia.org/wiki/Vincristine#cite_note-4http://en.wikipedia.org/wiki/United_Stateshttp://en.wikipedia.org/wiki/Food_and_Drug_Administrationhttp://en.wikipedia.org/wiki/Food_and_Drug_Administrationhttp://en.wikipedia.org/wiki/Eli_Lilly_and_Companyhttp://en.wikipedia.org/wiki/Teva_Pharmaceutical_Industrieshttp://en.wikipedia.org/wiki/Cancer_pain#Chemotherapy-induced_peripheral_neuropathyhttp://en.wikipedia.org/wiki/Hyponatremiahttp://en.wikipedia.org/wiki/Constipationhttp://en.wikipedia.org/wiki/Alopeciahttp://en.wikipedia.org/wiki/Foot_drophttp://en.wikipedia.org/wiki/Charcot-Marie-Tooth_diseasehttp://en.wikipedia.org/wiki/Vincristine#cite_note-1http://en.wikipedia.org/wiki/Intrathecalhttp://en.wikipedia.org/wiki/Paralysishttp://en.wikipedia.org/wiki/Encephalopathyhttp://en.wikipedia.org/wiki/Demyelinationhttp://en.wikipedia.org/wiki/Cerebrospinal_fluidhttp://en.wikipedia.org/wiki/Vincristine#cite_note-2http://en.wikipedia.org/wiki/Chinahttp://en.wikipedia.org/wiki/Cytarabinehttp://en.wikipedia.org/wiki/Methotrexatehttp://en.wikipedia.org/wiki/Vincristine#cite_note-3http://en.wikipedia.org/wiki/Vinca_roseahttp://en.wikipedia.org/wiki/Vinca_roseahttp://en.wikipedia.org/wiki/Diabetes_mellitushttp://en.wikipedia.org/wiki/Myelosuppressionhttp://en.wikipedia.org/wiki/Leukemiahttp://en.wikipedia.org/wiki/Aluminium_oxidehttp://en.wikipedia.org/wiki/Chromatographyhttp://en.wikipedia.org/wiki/Chloroformhttp://en.wikipedia.org/wiki/Vincristine#cite_note-4http://en.wikipedia.org/wiki/United_Stateshttp://en.wikipedia.org/wiki/Food_and_Drug_Administrationhttp://en.wikipedia.org/wiki/Eli_Lilly_and_Companyhttp://en.wikipedia.org/wiki/Teva_Pharmaceutical_Industries


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Vinlastine

From Wikipedia, the free encyclopediaJump to: navigation,search
http://en.wikipedia.org/wiki/Vinblastine#mw-headhttp://en.wikipedia.org/wiki/Vinblastine#mw-headhttp://en.wikipedia.org/wiki/Vinblastine#p-searchhttp://en.wikipedia.org/wiki/Vinblastine#mw-headhttp://en.wikipedia.org/wiki/Vinblastine#p-search


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Vin$lastine

Systematic (IUPAC) namedimethyl (*H,3H,H,!I,1*H,1I%& 1!&.(!S,S%& !&ethyl& !&hydro'y& &

(metho'ycar$onyl%

Clinical data

AHFS/Drugs.com monograph

MedlinePlus a+*

Pregnancy cat. (2% ("%egal status 4A8(%&only ("%

!outes "#clusi$elyintravenous


'ioa$ailaility n5a

Metaolism -epatic(K432&mediated%

Hal*lie *? hours (terminal%

"#cretion ".sho@/

;nh;.sho@/

(1%at is t%is2) ($eriy)
http://en.wikipedia.org/wiki/International_Union_of_Pure_and_Applied_Chemistry_nomenclaturehttp://en.wikipedia.org/wiki/American_Society_of_Health-System_Pharmacistshttp://en.wikipedia.org/wiki/Drugs.comhttp://www.drugs.com/monograph/vinblastine-sulfate.htmlhttp://en.wikipedia.org/wiki/MedlinePlushttp://www.nlm.nih.gov/medlineplus/druginfo/meds/a682848.htmlhttp://en.wikipedia.org/wiki/Pregnancy_categoryhttp://en.wikipedia.org/wiki/Australiahttp://en.wikipedia.org/wiki/United_Stateshttp://en.wikipedia.org/wiki/Regulation_of_therapeutic_goodshttp://en.wikipedia.org/wiki/Prescription_drughttp://en.wikipedia.org/wiki/United_Kingdomhttp://en.wikipedia.org/wiki/Prescription_drughttp://en.wikipedia.org/wiki/Prescription_drughttp://en.wikipedia.org/wiki/Prescription_drughttp://en.wikipedia.org/wiki/Prescription_drughttp://en.wikipedia.org/wiki/United_Stateshttp://en.wikipedia.org/wiki/United_Stateshttp://en.wikipedia.org/wiki/Route_of_administrationhttp://en.wikipedia.org/wiki/Intravenous_therapyhttp://en.wikipedia.org/wiki/Bioavailabilityhttp://en.wikipedia.org/wiki/Drug_metabolismhttp://en.wikipedia.org/wiki/Liverhttp://en.wikipedia.org/wiki/CYP3A4http://en.wikipedia.org/wiki/Biological_half-lifehttp://en.wikipedia.org/wiki/Excretionhttp://en.wikipedia.org/wiki/Kidneyhttp://en.wikipedia.org/wiki/CAS_registry_numberhttp://www.nlm.nih.gov/cgi/mesh/2009/MB_cgi?term=865-21-4&rn=1http://en.wikipedia.org/wiki/Anatomical_Therapeutic_Chemical_Classification_Systemhttp://en.wikipedia.org/wiki/ATC_code_L01http://www.whocc.no/atc_ddd_index/?code=L01CA01http://en.wikipedia.org/wiki/PubChemhttp://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=241903http://en.wikipedia.org/wiki/DrugBankhttp://www.drugbank.ca/drugs/DB00570http://en.wikipedia.org/wiki/ChemSpiderhttp://www.chemspider.com/Chemical-Structure.211446http://en.wikipedia.org/wiki/Unique_Ingredient_Identifierhttp://fdasis.nlm.nih.gov/srs/srsdirect.jsp?regno=5V9KLZ54CYhttp://fdasis.nlm.nih.gov/srs/srsdirect.jsp?regno=5V9KLZ54CYhttp://en.wikipedia.org/wiki/KEGGhttp://www.kegg.jp/entry/D08675http://www.kegg.jp/entry/D08675http://en.wikipedia.org/wiki/ChEBIhttps://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:27375https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:27375http://en.wikipedia.org/wiki/ChEMBLhttps://www.ebi.ac.uk/chembldb/index.php/compound/inspect/CHEMBL159http://en.wikipedia.org/wiki/NIAID_ChemDBhttp://chemdb.niaid.nih.gov/CompoundDetails.aspx?AIDSNO=002673http://en.wikipedia.org/wiki/Synonymhttp://en.wikipedia.org/wiki/Chemical_formulahttp://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Oxygenhttp://en.wikipedia.org/wiki/Molecular_masshttp://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specificationhttp://en.wikipedia.org/wiki/International_Chemical_Identifierhttp://en.wikipedia.org/wiki/Wikipedia:WikiProject_Chemicals/Chembox_validationhttp://en.wikipedia.org/w/index.php?title=Special:ComparePages&rev1=460778829&page2=Vinblastinehttp://en.wikipedia.org/w/index.php?title=File:Vinblastine.svg&page=1http://en.wikipedia.org/wiki/International_Union_of_Pure_and_Applied_Chemistry_nomenclaturehttp://en.wikipedia.org/wiki/American_Society_of_Health-System_Pharmacistshttp://en.wikipedia.org/wiki/Drugs.comhttp://www.drugs.com/monograph/vinblastine-sulfate.htmlhttp://en.wikipedia.org/wiki/MedlinePlushttp://www.nlm.nih.gov/medlineplus/druginfo/meds/a682848.htmlhttp://en.wikipedia.org/wiki/Pregnancy_categoryhttp://en.wikipedia.org/wiki/Australiahttp://en.wikipedia.org/wiki/United_Stateshttp://en.wikipedia.org/wiki/Regulation_of_therapeutic_goodshttp://en.wikipedia.org/wiki/Prescription_drughttp://en.wikipedia.org/wiki/United_Kingdomhttp://en.wikipedia.org/wiki/Prescription_drughttp://en.wikipedia.org/wiki/United_Stateshttp://en.wikipedia.org/wiki/Route_of_administrationhttp://en.wikipedia.org/wiki/Intravenous_therapyhttp://en.wikipedia.org/wiki/Bioavailabilityhttp://en.wikipedia.org/wiki/Drug_metabolismhttp://en.wikipedia.org/wiki/Liverhttp://en.wikipedia.org/wiki/CYP3A4http://en.wikipedia.org/wiki/Biological_half-lifehttp://en.wikipedia.org/wiki/Excretionhttp://en.wikipedia.org/wiki/Kidneyhttp://en.wikipedia.org/wiki/CAS_registry_numberhttp://www.nlm.nih.gov/cgi/mesh/2009/MB_cgi?term=865-21-4&rn=1http://en.wikipedia.org/wiki/Anatomical_Therapeutic_Chemical_Classification_Systemhttp://en.wikipedia.org/wiki/ATC_code_L01http://www.whocc.no/atc_ddd_index/?code=L01CA01http://en.wikipedia.org/wiki/PubChemhttp://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=241903http://en.wikipedia.org/wiki/DrugBankhttp://www.drugbank.ca/drugs/DB00570http://en.wikipedia.org/wiki/ChemSpiderhttp://www.chemspider.com/Chemical-Structure.211446http://en.wikipedia.org/wiki/Unique_Ingredient_Identifierhttp://fdasis.nlm.nih.gov/srs/srsdirect.jsp?regno=5V9KLZ54CYhttp://en.wikipedia.org/wiki/KEGGhttp://www.kegg.jp/entry/D08675http://en.wikipedia.org/wiki/ChEBIhttps://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:27375http://en.wikipedia.org/wiki/ChEMBLhttps://www.ebi.ac.uk/chembldb/index.php/compound/inspect/CHEMBL159http://en.wikipedia.org/wiki/NIAID_ChemDBhttp://chemdb.niaid.nih.gov/CompoundDetails.aspx?AIDSNO=002673http://en.wikipedia.org/wiki/Synonymhttp://en.wikipedia.org/wiki/Chemical_formulahttp://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Oxygenhttp://en.wikipedia.org/wiki/Molecular_masshttp://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specificationhttp://en.wikipedia.org/wiki/International_Chemical_Identifierhttp://en.wikipedia.org/wiki/Wikipedia:WikiProject_Chemicals/Chembox_validationhttp://en.wikipedia.org/w/index.php?title=Special:ComparePages&rev1=460778829&page2=Vinblastine


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Vinlastineis an antimicrotu$ule drugused to treat certain kinds of cancer, including

-odgkinDs lymphoma, non&small celllung cancer,$reast cancer, head and neck cancer,

and testicular cancer? ;t is also used to treat 9angerhans cell histiocytosis? Vin$lastine@as traditionally o$tained from Catharanthus roseus,also kno@n as Vinca rosea, a

8adagascar 4eri@inkle? ;t is generated in the plant $y the Eoining of t@o alkaloids

catharanthine and vindoline?.1/

Contents

1 -istory

* 4harmacology

3 8echanism of 2ction

;solation and "ynthesis

! ;ndications

+ "ee also

) Footnotes

History

Vin$lastine @as first isolated $y Ro$ert Mo$leand harles Chomas


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Mec%anism o Action

Che comple' of tu$lin and vin$lastine? Vin$lastine is sho@ed as yello@ stick?

8icrotu$ule disruptive drugs like vin$lastine,colcemid,nocoda0olehave $een reported

to act $y t@o mechanisms?./2t very lo@ concentrations they suppress microtu$ule

dynamics and at higher concentrations they reduce microtu$ule polymer mass? Recentfindings indicate that they also produce microtu$ule fragments $y stimulating

microtu$ule minus&end detachment from their organi0ing centers? ose&response studies

further indicate that enhanced microtu$ule detachment from spindle poles correlate $est@ith cytoto'icity?.!/

Isolation and Synt%esis

Vin$lastine may $e isolated from the 8adagascar 4eri@inkle (Catharanthus roseus%,

along @ith several of its precursors& catharanthine and vindoline? >'traction is costly andyields of vin$lastine and its precursors are lo@? >nantioselective synthesis has $een of

considera$le interest in recent years, as the natural mi'ture of isomers is not an

economical source for the reNuired 1+O", 1OR stereochemistry of $iologically activevin$lastine? ;nitially, the approach depends upon an enantioselective "harpless

epo'idation, @hich sets the stereochemistry at *#? Che desired configuration around

1+ and 1 can then $e fi'ed during the ensuing steps? ;n this path@ay, vin$lastine is

constructed $y a series of cycli0ation and coupling reactions @hich create the reNuiredstereochemistry? Che overall yield may $e as great as **7, @hich makes this synthetic

approach more attractive than e'traction from natural sources, @hose overall yield is

a$out 1#7?.+/"tereochemistry is controlled through a mi'ture of chiral agents ("harplesscatalysts%, and reaction conditions (temperature, and selected enantiopure starting

materials%?.)/
http://en.wikipedia.org/wiki/Colcemidhttp://en.wikipedia.org/wiki/Colcemidhttp://en.wikipedia.org/wiki/Nocodazolehttp://en.wikipedia.org/wiki/Nocodazolehttp://en.wikipedia.org/wiki/Nocodazolehttp://en.wikipedia.org/wiki/Vinblastine#cite_note-3http://en.wikipedia.org/wiki/Vinblastine#cite_note-4http://en.wikipedia.org/wiki/Vinblastine#cite_note-5http://en.wikipedia.org/wiki/Vinblastine#cite_note-6http://en.wikipedia.org/wiki/File:Tublin%26vinblastin-1Z2B.pnghttp://en.wikipedia.org/wiki/File:Tublin%26vinblastin-1Z2B.pnghttp://en.wikipedia.org/wiki/Colcemidhttp://en.wikipedia.org/wiki/Nocodazolehttp://en.wikipedia.org/wiki/Vinblastine#cite_note-3http://en.wikipedia.org/wiki/Vinblastine#cite_note-4http://en.wikipedia.org/wiki/Vinblastine#cite_note-5http://en.wikipedia.org/wiki/Vinblastine#cite_note-6


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Indications

Vin$lastine is a component of a num$er of chemotherapy regimens, including 2


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-ama sistematis (IUPAC)

asam *&asetil$en0oat

Data &linis

at. &e%amilan (2%("%

Status %u&um nscheduled(2%G"9 (%AC("%

!ute

8ost commonly oral, also rectal? 9ysine

acetylsalicylatemay $e given ;Vor;8


'ioa$ailailitas Rapidly and completely a$sor$ed

I&atan ,rotein ?+7

Metaolisme -epatic

3a&tu ,aru%

3##P+!# mg dose: 3?1P3?* h

1 g dose: ! h

* g dose: h

"&s&resi Renal

Pengenal

-omor CAS !#&)&*

ode A+C 2#1 2#!


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SMI"S e8oleculesQ4u$hem

Data isi&

e,adatan 1?# g5cm

+iti& leur 13! S (*)! SF%

+iti& didi% 1# S (* SF% (decomposes%

elarutandalam

air3 mg5m9 (*# S%

As,irinatau asam asetilsalisilat(asetosal% adalah seEenis o$atturunan darisalisilatyang

sering digunakan se$agai senya@aanalgesik(penahan rasa sakitatau nyeri minor%,

antipiretik(terhadap demam%, dan anti&inflamasi(peradangan%? 2spirin Euga memilikiefek antikoagulandan dapat digunakan dalam dosis rendah dalam tempo lama untuk

mencegah serangan Eantung?epopuleran penggunaan aspirin se$agai o$at dimulai pada

tahun 11ketika terEadi pandemik flu di $er$agai @ilayah dunia? .1/

2@al mula penggunaan aspirin se$agai o$at diprakarsai oleh -ippocratesyangmenggunakan ekstrak tum$uhan @illo@untuk menyem$uhkan $er$agai penyakit?

emudian senya@a ini dikem$angkan oleh perusahaan


11/50

Sejarah penemuan

"enya@a alami dari tum$uhanyang digunakan se$agai o$at ini telah ada seEak a@al mula

perada$an manusia? i mulai pada perada$an8esirkuno, $angsa terse$ut telahmenggunakan suatu senya@a yang $erasal dari daun @illo@untuk menekan rasa sakit?

4ada era yang sama, $angsa "umeriaEuga telah menggunakan senya@a yang serupauntuk mengatasi $er$agai Eenis penyakit? -al ini tercatat dalam ukiran&ukiran pada$e$atuan di daerah terse$ut?


12/50

Feli' -offmann $ukanlah orang pertama yang $erusaha untuk menciptakan senya@a

aspirin ini? "e$elumnya pada tahun 1!3, seorang ilmu@an 4erancis $ernama Frederick

Gerhardt telah menco$a untuk menciptakan suatu senya@a $aru dari ga$ungan asetilkloridadan sodium salisilat?.)/2spirin diEual se$agai o$at pada tahun 1 setelah Feli'

-offmann $erhasil memodifikasi asam salisilat, senya@a yang ditemukan dalam kulit

kayu dedalu?


13/50

Jenis&Eenis o$at analgesikyang lain ialah:

4arasetamol

odeina

>sterifikasi 2spirin

2spirin ini di$uat dengan cara esterifikasi, dimana $ahan aktif dari aspirin yaitu asam

salisitat direaksikan dengan asam asetat anhidrad atau dapat Euga direaksikan dengan

asam asetat glacial $ila asam asetat anhidrad sulit untuk ditemukan? 2sam asetat anhidradini dapat digantikan dengan asam asetat glacial karena asam asetat glacial ini $ersifat

murni dan tidak mengandung air selain itu asam asetat anhidrad Euga ter$uat dari dua

asan asetat galsial sehingga pada pereaksian volumenya semua digandakan? 4ada proses

pem$uatan reaksi esterifikasi ini di$antu oleh suatu katalis asam untuk mempercepatreaksi? Cetapi pada penam$ahan katalis ini tidak terlalu $erefek maka dilakukan lah

pemanasan untuk mempercepat reaksinya? 4ada pem$uatan aspirin Euga ditam$ahkan air

untuk melakukan rekristalisasi $erlangsung cepat dan akan ter$entuk endapan? >ndapan

inilah yang merupakanaspirin?

5uinineFrom Wikipedia, the free encyclopedia

Jump to: navigation,search

Mot to $e confused @ith Nuinone?

=uinine
http://id.wikipedia.org/wiki/Analgesikhttp://id.wikipedia.org/wiki/Parasetamolhttp://id.wikipedia.org/wiki/Kodeinahttp://id.wikipedia.org/w/index.php?title=Esterifikasi_Aspirin&action=edit&redlink=1http://en.wikipedia.org/wiki/Quinine#mw-headhttp://en.wikipedia.org/wiki/Quinine#mw-headhttp://en.wikipedia.org/wiki/Quinine#p-searchhttp://en.wikipedia.org/wiki/Quinonehttp://id.wikipedia.org/wiki/Analgesikhttp://id.wikipedia.org/wiki/Parasetamolhttp://id.wikipedia.org/wiki/Kodeinahttp://id.wikipedia.org/w/index.php?title=Esterifikasi_Aspirin&action=edit&redlink=1http://en.wikipedia.org/wiki/Quinine#mw-headhttp://en.wikipedia.org/wiki/Quinine#p-searchhttp://en.wikipedia.org/wiki/Quinone


14/50

Systematic (IUPAC) name(R%&(+&metho'yNuinolin&&yl%((1R,*",R,!"%&!&vinylNuinuclidin&*&

yl%methanol

Clinical data

+rade names =ualaNuin

AHFS/Drugs.com monographMedlinePlus a+*3**

Pregnancy cat. ("2%, (2u%

egal status R'&only "2

!outes Aral,intravenous


'ioa$ailaility )+ to 7

Protein inding 6)#7

Metaolism-epatic(mostly K432and

K4*1&mediated%

Hal*lie 61 hours"#cretion Renal(*#7%

Identiiers

CAS numer 13#&!

A+C code 8# 22#1 4#1


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Drug'an& 8


16/50

3 osing and indication

2dverse effects

o ?1 Mon&a$ortifacient

o ?* isease interactions

o ?3 -earing impairment

! Regulation $y the nited "tates Food and rug 2dministration + Monmedical uses of Nuinine

o +?1 'ternal links

Mec%anism o action againstP. falciparum

2s @ith other Nuinoline antimalarial drugs, the mechanism of action of Nuinine has not

$een fully resolved? Che most @idely accepted hypothesis of its action is $ased on the

@ell&studied and closely related Nuinoline drug,chloroNuine? Chis model involves theinhi$ition of hemo0oin$iocrystalli0ation,@hich facilitates the aggregation ofcytoto'ic

heme? Free cytoto'ic heme accumulates in the parasites, causing their deaths?

History

=uinine.*/is an effective muscle rela'ant, long used $y the =uechua,@ho are indigenousto 4eru, to halt shivering due to lo@ temperatures? Che 4eruvians @ould mi' the ground

$ark of cinchonatrees @ith s@eetened @ater to offset the $arkDs $itter taste, thus

producing tonic @ater?

1th&century illustration of Cinchona calisaya

=uinine has $een used in une'tracted form $y >uropeans since at least the early 1)thcentury? ;t @as first used to treat malaria in Rome in 1+31?.3/uring the 1)th century,

malaria @as endemic to the s@ampsand marshessurrounding the city of Rome? 8alaria@as responsi$le for the deaths of severalpopes, many cardinalsand countless common

Roman citi0ens? 8ost of theprieststrained in Rome had seen malaria victims and @ere

familiar @ith the shivering$rought on $y the fe$rilephase of the disease? Che Jesuit$rother 2gostino "alum$rino (1!+1P1+*%, an apothecary$y training @ho lived in 9ima,

o$served the =uechua using the $ark of the cinchona tree for that purpose? While its
http://en.wikipedia.org/wiki/Quinine#Dosing_and_indicationhttp://en.wikipedia.org/wiki/Quinine#Adverse_effectshttp://en.wikipedia.org/wiki/Quinine#Non-abortifacienthttp://en.wikipedia.org/wiki/Quinine#Disease_interactionshttp://en.wikipedia.org/wiki/Quinine#Hearing_impairmenthttp://en.wikipedia.org/wiki/Quinine#Regulation_by_the_United_States_Food_and_Drug_Administrationhttp://en.wikipedia.org/wiki/Quinine#Nonmedical_uses_of_quininehttp://en.wikipedia.org/wiki/Quinine#Beverageshttp://en.wikipedia.org/wiki/Quinine#Scientifichttp://en.wikipedia.org/wiki/Quinine#Otherhttp://en.wikipedia.org/wiki/Quinine#See_alsohttp://en.wikipedia.org/wiki/Quinine#Referenceshttp://en.wikipedia.org/wiki/Quinine#Further_readinghttp://en.wikipedia.org/wiki/Quinine#External_linkshttp://en.wikipedia.org/wiki/Chloroquinehttp://en.wikipedia.org/wiki/Chloroquinehttp://en.wikipedia.org/wiki/Hemozoinhttp://en.wikipedia.org/wiki/Biocrystallizationhttp://en.wikipedia.org/wiki/Biocrystallizationhttp://en.wikipedia.org/wiki/Cytotoxichttp://en.wikipedia.org/wiki/Cytotoxichttp://en.wikipedia.org/wiki/Hemehttp://en.wikipedia.org/wiki/Quinine#cite_note-1http://en.wikipedia.org/wiki/Quechuashttp://en.wikipedia.org/wiki/Quechuashttp://en.wikipedia.org/wiki/Peruhttp://en.wikipedia.org/wiki/Cinchonahttp://en.wikipedia.org/wiki/Tonic_waterhttp://en.wikipedia.org/wiki/Tonic_waterhttp://en.wikipedia.org/wiki/Quinine#cite_note-pmid17291968-2http://en.wikipedia.org/wiki/Swamphttp://en.wikipedia.org/wiki/Marshhttp://en.wikipedia.org/wiki/Romehttp://en.wikipedia.org/wiki/Popehttp://en.wikipedia.org/wiki/Popehttp://en.wikipedia.org/wiki/Cardinal_(Catholicism)http://en.wikipedia.org/wiki/Priesthttp://en.wikipedia.org/wiki/Shiveringhttp://en.wiktionary.org/wiki/febrilehttp://en.wikipedia.org/wiki/Jesuithttp://en.wikipedia.org/wiki/Apothecaryhttp://en.wikipedia.org/wiki/Limahttp://en.wikipedia.org/wiki/Limahttp://en.wikipedia.org/wiki/File:Cinchona_calisaya_-_K%C3%B6hler%E2%80%93s_Medizinal-Pflanzen-179.jpghttp://en.wikipedia.org/wiki/File:Cinchona_calisaya_-_K%C3%B6hler%E2%80%93s_Medizinal-Pflanzen-179.jpghttp://en.wikipedia.org/wiki/Quinine#Dosing_and_indicationhttp://en.wikipedia.org/wiki/Quinine#Adverse_effectshttp://en.wikipedia.org/wiki/Quinine#Non-abortifacienthttp://en.wikipedia.org/wiki/Quinine#Disease_interactionshttp://en.wikipedia.org/wiki/Quinine#Hearing_impairmenthttp://en.wikipedia.org/wiki/Quinine#Regulation_by_the_United_States_Food_and_Drug_Administrationhttp://en.wikipedia.org/wiki/Quinine#Nonmedical_uses_of_quininehttp://en.wikipedia.org/wiki/Quinine#Beverageshttp://en.wikipedia.org/wiki/Quinine#Scientifichttp://en.wikipedia.org/wiki/Quinine#Otherhttp://en.wikipedia.org/wiki/Quinine#See_alsohttp://en.wikipedia.org/wiki/Quinine#Referenceshttp://en.wikipedia.org/wiki/Quinine#Further_readinghttp://en.wikipedia.org/wiki/Quinine#External_linkshttp://en.wikipedia.org/wiki/Chloroquinehttp://en.wikipedia.org/wiki/Hemozoinhttp://en.wikipedia.org/wiki/Biocrystallizationhttp://en.wikipedia.org/wiki/Cytotoxichttp://en.wikipedia.org/wiki/Hemehttp://en.wikipedia.org/wiki/Quinine#cite_note-1http://en.wikipedia.org/wiki/Quechuashttp://en.wikipedia.org/wiki/Peruhttp://en.wikipedia.org/wiki/Cinchonahttp://en.wikipedia.org/wiki/Tonic_waterhttp://en.wikipedia.org/wiki/Quinine#cite_note-pmid17291968-2http://en.wikipedia.org/wiki/Swamphttp://en.wikipedia.org/wiki/Marshhttp://en.wikipedia.org/wiki/Romehttp://en.wikipedia.org/wiki/Popehttp://en.wikipedia.org/wiki/Cardinal_(Catholicism)http://en.wikipedia.org/wiki/Priesthttp://en.wikipedia.org/wiki/Shiveringhttp://en.wiktionary.org/wiki/febrilehttp://en.wikipedia.org/wiki/Jesuithttp://en.wikipedia.org/wiki/Apothecaryhttp://en.wikipedia.org/wiki/Lima


17/50

effect in treating malaria (and hence malaria&induced shivering% @as unrelated to its

effect in controlling shivering from rigors,it @as still a successful medicine for malaria?

2t the first opportunity, "alum$rino sent a small Nuantity to Rome to test as a malariatreatment? ;n the years that follo@ed, cinchona $ark, kno@n as JesuitDs $arkor 4eruvian

$ark, $ecame one of the most valua$le commodities shipped from 4eru to >urope?

Che form of Nuinine most effective in treating malaria @as found $y harles 8arie de 9a

ondaminein 1)3)?./.!/=uinine @as isolated and named in 1*# $y French researchers4ierre Joseph 4elletierand Joseph uropeans? =uinine

had $een said to $e the prime reason 2frica ceased to $e kno@n as the B@hite manDs

graveB? 2n historian has stated, Bit @as NuinineDs efficacy that gave colonists freshopportunities to s@arm into the Gold oast,Migeriaand other parts of @est 2fricaB?.)/

Co maintain their monopoly on cinchona $ark, 4eru and surrounding countries $egan

outla@ing the e'port of cinchona seeds and saplings $eginning in the early 1th century?Che utch government persisted in its attempt to smuggle the seeds, and $y the 13#s

utch plantations in Java@ere producing ** million pounds of cinchona $ark, or )7 of

the @orldDs Nuinine production?.)/uringWorld War ;;, 2llied po@ers @ere cut off fromtheir supply of Nuinine @hen the Germans conNuered the Metherlands and the Japanese

controlled the 4hilippinesand ;ndonesia?Che nited "tates had managed to o$tain four

million cinchona seeds from the 4hilippines and $egan operation of cinchona plantations

in osta Rica? Monetheless, such supplies came too late tens of thousands of " troopsin 2frica and the "outh 4acific died due to the lack of Nuinine?.)/espite controlling the

supply, the Japanese did not make effective use of Nuinine, and thousands of Japanesetroops in the south@est 4acific died as a result?./

Synt%etic 6uinine

8ain article: Nuinine total synthesis

Ro$ert


18/50

inchona treesremain the only economically practical source of Nuinine? -o@ever, under

@artime pressure, research to@ards its synthetic production @as undertaken? 2 formal

chemical synthesis @as accomplished in 1 $y 2merican chemistsR?? oering?./"ince then, several more efficient Nuinine total syntheseshave $een

achieved,.1#/$ut none of them can compete in economic terms @ith isolation of the

alkaloid from natural sources? Che first syntheticorganicdye, mauveine, @as discovered$y William -enry 4erkinin 1!+ @hile he @as attempting to synthesi0e Nuinine?

Dosing and indication

2s of *##+, Nuinine is no longer recommended $y the W-A as first&line treatment for

malaria, and should $e used only @hen artemisininsare not availa$le?.11/.1*/.13/.1/

=uinine is a $asic amineand is al@ays presented as a salt? Various e'isting preparations

include the hydrochloride,dihydrochloride, sulfate, $isulfate andgluconate?Chis makes

Nuinine dosing complicated, since each of the salts has a different @eight?

Che follo@ing amounts of each salt form contain eNual amounts of Nuinine:

Nuinine $ase 1## mg

Nuinine $isulfate 1+ mg

Nuinine dihydrochloride 1** mg

Nuinine hydrochloride 111 mg

Nuinine sulfate (actually (Nuinine%*-*"AU*-*A% 1*1 mg

Nuinine gluconate 1+# mg

2ll Nuinine salts may $e given orally or intravenously(;V% Nuinine gluconate may also

$e given intramuscularly(;8% or rectally (4R%?.1!/.1+/Che main pro$lem @ith the rectalroute is the dose can $e e'pelled $efore it is completely a$sor$ed in practice, this is

corrected $y giving a half dose again?

Che ;V dose of Nuinine is mg5kg of Nuinine $ase every eight hours the ;8 dose is

1*? mg5kg of Nuinine $ase t@ice daily the 4R dose is *# mg5kg of Nuinine $ase t@ice

daily? Creatment should $e given for seven days? For at least the ;V formulation, aloading dose of *# mg5kg is reNuired?

Che preparations availa$le in the are Nuinine sulfate (*##&mg or 3##&mg ta$lets% and

Nuinine hydrochloride (3## mg5ml for inEection%? =uinine is not licensed for ;8 or 4R

use in the nited ingdom? Che adult dose in the is +## mg Nuinine dihydrochloride;V or +## mg Nuinine sulfate orally every eight hours? For nocturnal leg cramps, the

dosage is *##P3## mg at night?.1)/

;n the nited "tates, Nuinine sulfate is commercially availa$le in 3*&mg ta$lets under

the $rand name =ualaNuin the adult dose is t@o ta$lets every eight hours? Mo inEecta$lepreparation of Nuinine is licensed in the "Nuinidineis used instead?.1/.1/
http://en.wikipedia.org/wiki/Cinchonahttp://en.wikipedia.org/wiki/Robert_Burns_Woodwardhttp://en.wikipedia.org/wiki/Robert_Burns_Woodwardhttp://en.wikipedia.org/wiki/W.E._Doeringhttp://en.wikipedia.org/wiki/Quinine#cite_note-Woodward1944-8http://en.wikipedia.org/wiki/Quinine#cite_note-Woodward1944-8http://en.wikipedia.org/wiki/Quinine_total_synthesishttp://en.wikipedia.org/wiki/Quinine#cite_note-9http://en.wikipedia.org/wiki/Quinine#cite_note-9http://en.wikipedia.org/wiki/Organic_chemistryhttp://en.wikipedia.org/wiki/Organic_chemistryhttp://en.wikipedia.org/wiki/Dyehttp://en.wikipedia.org/wiki/Dyehttp://en.wikipedia.org/wiki/Mauveinehttp://en.wikipedia.org/wiki/William_Henry_Perkinhttp://en.wikipedia.org/wiki/Artemisininhttp://en.wikipedia.org/wiki/Quinine#cite_note-10http://en.wikipedia.org/wiki/Quinine#cite_note-11http://en.wikipedia.org/wiki/Quinine#cite_note-12http://en.wikipedia.org/wiki/Quinine#cite_note-13http://en.wikipedia.org/wiki/Aminehttp://en.wikipedia.org/wiki/Hydrochloridehttp://en.wikipedia.org/wiki/Hydrochloridehttp://en.wikipedia.org/wiki/Sulfatehttp://en.wikipedia.org/wiki/Gluconatehttp://en.wikipedia.org/wiki/Gluconatehttp://en.wikipedia.org/wiki/Gluconatehttp://en.wikipedia.org/wiki/Intravenous_therapyhttp://en.wikipedia.org/wiki/Intramuscular_injectionhttp://en.wikipedia.org/wiki/Intramuscular_injectionhttp://en.wikipedia.org/wiki/Quinine#cite_note-Barennes1996-14http://en.wikipedia.org/wiki/Quinine#cite_note-Barennes1996-14http://en.wikipedia.org/wiki/Quinine#cite_note-Barennes2006-15http://en.wikipedia.org/wiki/Quinine#cite_note-16http://en.wikipedia.org/wiki/Quinidinehttp://en.wikipedia.org/wiki/Quinidinehttp://en.wikipedia.org/wiki/Quinine#cite_note-17http://en.wikipedia.org/wiki/Quinine#cite_note-18http://en.wikipedia.org/wiki/Cinchonahttp://en.wikipedia.org/wiki/Robert_Burns_Woodwardhttp://en.wikipedia.org/wiki/W.E._Doeringhttp://en.wikipedia.org/wiki/Quinine#cite_note-Woodward1944-8http://en.wikipedia.org/wiki/Quinine_total_synthesishttp://en.wikipedia.org/wiki/Quinine#cite_note-9http://en.wikipedia.org/wiki/Organic_chemistryhttp://en.wikipedia.org/wiki/Dyehttp://en.wikipedia.org/wiki/Mauveinehttp://en.wikipedia.org/wiki/William_Henry_Perkinhttp://en.wikipedia.org/wiki/Artemisininhttp://en.wikipedia.org/wiki/Quinine#cite_note-10http://en.wikipedia.org/wiki/Quinine#cite_note-11http://en.wikipedia.org/wiki/Quinine#cite_note-12http://en.wikipedia.org/wiki/Quinine#cite_note-13http://en.wikipedia.org/wiki/Aminehttp://en.wikipedia.org/wiki/Hydrochloridehttp://en.wikipedia.org/wiki/Sulfatehttp://en.wikipedia.org/wiki/Gluconatehttp://en.wikipedia.org/wiki/Intravenous_therapyhttp://en.wikipedia.org/wiki/Intramuscular_injectionhttp://en.wikipedia.org/wiki/Quinine#cite_note-Barennes1996-14http://en.wikipedia.org/wiki/Quinine#cite_note-Barennes2006-15http://en.wikipedia.org/wiki/Quinine#cite_note-16http://en.wikipedia.org/wiki/Quinidinehttp://en.wikipedia.org/wiki/Quinine#cite_note-17http://en.wikipedia.org/wiki/Quinine#cite_note-18


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Ad$erse eects

8ain article: inchonism

=uinine can, in therapeutic doses, cause cinchonism in rare cases, it may even cause

death (usually $ypulmonary edema%? Che development of mild cinchonism is not areason for stopping or interrupting Nuinine therapy, and the patient should $e reassured?


20/50

Hearing im,airment

"ome studies have related the use of Nuinine and hearing impairment,particularly high&

freNuency loss, $ut it has not $een conclusively esta$lished @hether such impairment is

temporary or permanent?.*)/

!egulation y t%e United States Food and Drug

Administration

From 1+ to 1*, the " Food and rug 2dministration(F2% received 1!) reports of

health pro$lems related to Nuinine use, including *3 @hich had resulted in death?.*/;n1, the F2 $anned the use of over&the&counterNuinine as a treatment for nocturnal

leg cramps? 4fi0er4harmaceuticalshad $een selling the $rand name 9egatrin for this

purpose? octors may still prescri$e Nuinine, $ut the F2 has ordered firms to stopmarketing unapproved drug products containing Nuinine? Che F2 is also cautioning

consumers a$out off&la$el use of Nuinine to treat leg cramps? =uinine is approved fortreatment of malaria, $ut is also commonly prescri$ed to treat leg cramps and similarconditions?


21/50

'e$erages

=uinine is a flavour component of tonic @aterand$itter lemon?An the soda gun $ehind

most $ars, tonic @ater is designated $y the letter B=B representing Nuinine? 2ccording to

tradition, the $itter taste of antimalarial Nuinine tonic led


22/50

Digo#in

From Wikipedia, the free encyclopedia

Jump to: navigation,searchMot to $e confused @ith io'in?

igo'in
http://en.wikipedia.org/wiki/Digoxin#mw-headhttp://en.wikipedia.org/wiki/Digoxin#mw-headhttp://en.wikipedia.org/wiki/Digoxin#p-searchhttp://en.wikipedia.org/wiki/Dioxinhttp://en.wikipedia.org/w/index.php?title=File:Digoxin_structure.svg&page=1http://en.wikipedia.org/wiki/Digoxin#mw-headhttp://en.wikipedia.org/wiki/Digoxin#p-searchhttp://en.wikipedia.org/wiki/Dioxin


23/50

Systematic (IUPAC) name&.(3S,!%,%,S,1#S,1*%,13S,1S%&3&.(*S,S,!%,+%%&!&.(*S,S,!%,+%%&!&.(*S,S,!%,+%%&,!&

dihydro'y&+&methyl&o'an&*&yl/o'y&&hydro'y&+&methyl&o'an&*&yl/o'y&&hydro'y&+&methyl&o'an&

*&yl/o'y&1*,1&dihydro'y&1#,13&dimethyl&1,*,3,,!,+,),,,11,1*,1!,1+,1)&tetradecahydrocyclopenta.a/phenanthren&1)&yl/&!'&furan&*&one

Clinical data

+rade names 9ano'inAHFS/Drugs.com monograph

MedlinePlus a+*3#1

Pregnancy cat. 2 (2u%, (?"?%

egal status " (2u%, 4A8 (%, &only (?"?%

!outes Aral, ;ntravenous


'ioa$ailaility +# to #7 (Aral%

Protein inding *!7

Metaolism -epatic(1+7%

Hal*lie3+ to hours(patients @ith normalrenal function%3?! to ! days(patients @ith impaired renal function%

"#cretion Renal

Identiiers

CAS numer *#3#&)!&!

A+C code #1 22#!

PuC%em ; *)*3!

Drug'an& 8


24/50

conditions, namely atrial fi$rillation,atrial flutterand sometimes heart failurethat cannot

$e controlled $y other medication? igo'in preparations are commonly marketed under

the trade names9ano'in, igitek, and 9ano'icaps? ;t is also availa$le as a #?#! mg5mloral solution and #?*! mg5ml or #?! mg5ml inEecta$le solution? ;t is marketed $y

Gla'o"mithlineand many other pharmaceutic manufacturers?

Contents

1 8edical use

* 4harmacokinetic properties

3 2dverse effects

2ctions

! 8echanism of action

+ "ociety and culture

) References

Further reading

>'ternal links

Medical use

Coday, the most common indications for digo'in areatrial fi$rillationand atrial flutter

@ith rapid ventricular response?


25/50

igo'in is usually given $y mouth, $ut can also $e given $y ;V inEection in urgent

situations (the ;V inEection should $e slo@, and heart rhythm should $e monitored%?

While ;V therapy may $e $etter tolerated (less nausea%, digo'in has a very longdistri$ution half&life into the cardiac tissue, @hich @ill delay its onset of action $y a

num$er of hours? Che half&life is a$out 3+ hours, digo'in is given once daily, usually in

1*!&g or *!#&g doses?

;n patients @ith decreased kidney function, the half&life is considera$ly longer, calling fora reduction in dose or a s@itch to a different glycoside, such asdigito'in(not availa$le in

the nited "tates%, @hich has a much longer elimination half&lifeof around seven days,

$ut is mainly eliminated from the $ody via theliver, and thus not affected $y changes inkidney function?

>ffective plasma levels vary depending on the medical indication? Forcongestive heart

failure,levels $et@een #?! and 1?# ng5ml are recommended?.+/Chis recommendation is

$ased onpost hocanalysis of prospective trials, suggesting higher levels may $e

associated @ith increased mortality rates? For heart rate control (atrial fi$rillation%,plasma levels are less defined and are generally titrated to a goal heart rate? Cypically,

digo'in levels are considered therapeutic for heart rate control $et@een 1?# and *?# ng5ml?;n suspected to'icity or ineffectiveness, digo'in levels should $e monitored? 4lasma

potassium levels also need to $e closely controlled (see side effects $elo@%?

=uinidine, verapamil, and amiodarone increases plasma levels of digo'in ($y displacing

tissue $inding sites and depressing renal digo'in clearance%, so plasma digo'in must $emonitored carefully?

Researchers at Kale niversity looked at data from an earlier study to see if digo'in

affected men and @omen differently? Chat study determined digo'in, @hich has $eenused for centuries and makes the heart contract more forcefully, did not reduce deathsoverall, $ut did result in less hospitali0ation? Researcher r? -arlan rumhol0 said they

@ere surprised to find @omen in the study @ho took digo'in died Bmore freNuentlyB

(337% than @omen @ho took aplace$opill (*7%? Chey calculated digo'in increased therisk of death in @omen $y *37? Chere @as no difference in the death rate for men in the

study?

igo'in is also used as a standard control su$stance to test for p&glycoproteininhi$ition?

Ad$erse eects

8ain article: igo'in to'icity

Che occurrence of adverse drug reactionsis common, o@ing to its narro@ therapeutic

inde'(the margin $et@een effectiveness and to'icity%? 2dverse effects are concentration&

dependent, and are rare @hen plasma digo'in concentration is #? g5l?.)/Chey are alsomore common in patients @ith lo@ potassium levels (hypokalemia%, since digo'in

normally competes @ith Xions for the same $inding site on theMaX 5X 2C4asepump?
http://en.wikipedia.org/wiki/Digitoxinhttp://en.wikipedia.org/wiki/Digitoxinhttp://en.wikipedia.org/wiki/Elimination_half-lifehttp://en.wikipedia.org/wiki/Elimination_half-lifehttp://en.wikipedia.org/wiki/Liverhttp://en.wikipedia.org/wiki/Liverhttp://en.wikipedia.org/wiki/Congestive_heart_failurehttp://en.wikipedia.org/wiki/Congestive_heart_failurehttp://en.wikipedia.org/wiki/Congestive_heart_failurehttp://en.wikipedia.org/wiki/Congestive_heart_failurehttp://en.wikipedia.org/wiki/Digoxin#cite_note-5http://en.wikipedia.org/wiki/Digoxin#cite_note-5http://en.wikipedia.org/wiki/Atrial_fibrillationhttp://en.wikipedia.org/wiki/Placebohttp://en.wikipedia.org/wiki/P-glycoproteinhttp://en.wikipedia.org/wiki/Digoxin_toxicityhttp://en.wikipedia.org/wiki/Adverse_drug_reactionhttp://en.wikipedia.org/wiki/Adverse_drug_reactionhttp://en.wikipedia.org/wiki/Therapeutic_indexhttp://en.wikipedia.org/wiki/Therapeutic_indexhttp://en.wikipedia.org/wiki/Digoxin#cite_note-Rossi-6http://en.wikipedia.org/wiki/Hypokalemiahttp://en.wikipedia.org/wiki/NaKATPasehttp://en.wikipedia.org/wiki/NaKATPasehttp://en.wikipedia.org/wiki/NaKATPasehttp://en.wikipedia.org/wiki/NaKATPasehttp://en.wikipedia.org/wiki/NaKATPasehttp://en.wikipedia.org/wiki/Digitoxinhttp://en.wikipedia.org/wiki/Elimination_half-lifehttp://en.wikipedia.org/wiki/Liverhttp://en.wikipedia.org/wiki/Congestive_heart_failurehttp://en.wikipedia.org/wiki/Congestive_heart_failurehttp://en.wikipedia.org/wiki/Digoxin#cite_note-5http://en.wikipedia.org/wiki/Atrial_fibrillationhttp://en.wikipedia.org/wiki/Placebohttp://en.wikipedia.org/wiki/P-glycoproteinhttp://en.wikipedia.org/wiki/Digoxin_toxicityhttp://en.wikipedia.org/wiki/Adverse_drug_reactionhttp://en.wikipedia.org/wiki/Therapeutic_indexhttp://en.wikipedia.org/wiki/Therapeutic_indexhttp://en.wikipedia.org/wiki/Digoxin#cite_note-Rossi-6http://en.wikipedia.org/wiki/Hypokalemiahttp://en.wikipedia.org/wiki/NaKATPase


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ommon adverse effects (Y17 of patients% include: loss of appetite,nausea, vomitingand

diarrheaas gastrointestinal motility increases? Ather common effects are$lurred vision,

visual distur$ances (yello@&green halos and pro$lems @ith color perception%, confusion,dro@siness,di00iness,insomnia,nightmares, agitation, and depression,as @ell as a

higher acute sense of sensual activities?./9ess freNuent adverse effects (#?17P17%

include: acutepsychosis,delirium,amnesia,convulsions, shortened =R" comple', atrialor ventricular e'trasystoles, paro'ysmal atrial tachycardia@ith 2V $lock,ventricular

tachycardia or fi$rillation, and heart $lock?.)/Rarely, digo'in has $een sho@n to cause

throm$ocytopenia?Gynaecomastia(enlargement of $reast tissue% is mentioned in manyte't$ooks as a side effect, thought to $e due to the estrogen&like steroid moiety of the

digo'in molecule,./$ut @hen systematically sought, the evidence for this is eNuivocal?.1#/

Che pharmacological actions of digo'in usually result in electrocardiogramchanges,

including "C depression or C @ave inversion, @hich do not indicate to'icity? 4R intervalprolongation, ho@ever, may $e a sign of digo'in to'icity? 2dditionally, increased

intracellular a*Xmay cause a type of arrhythmia called$igeminy(coupled $eats%,

eventually ventricular tachycardiaor fi$rillation? Che com$ination of increased (atrial%

arrhythmogenesis and inhi$ited atrioventricular conduction (for e'ample paro'ysmalatrial tachycardia @ith 2&V $lock & so&called B42C @ith $lockB% is said to $e

pathognomonic(i?e? diagnostic% of digo'in to'icity?.11/

2n often descri$ed, $ut rarely seen, adverse effect of digo'in is a distur$ance of colorvision (mostly yello@ and green% called 'anthopsia?Vincent van GoghDs BKello@ 4eriodB

may have someho@ $een influenced $y concurrent digitalis therapy? Ather oculoto'ic

effects of digo'in include generali0ed $lurry vision, as @ell as seeing a BhaloB aroundeach point of light?.1*/Che latter effect can also $e seen in van GoghDs "tarry Might?

>vidence of van GoghDs digo'in use is supported $y multiple self portraits that include

the fo'glove plant,from @hich digo'in is o$tained? (e?g? 4ortrait of r? Gachet%

igo'in plasma concentrations may increase @hile on antimalarialmedicationhydro'ychloroNuine($ased on t@o case reports from 1*%?.13/

;n overdose, the usual supportive measures are needed? ;f arrhythmias prove trou$lesome,

or malignant hyperkalaemia occurs (ine'ora$ly rising potassium level due to paralysis of

the cell mem$rane&$ound, 2C4ase&dependent Ma5 pumps%, the specific antidote isantidigo'in (anti$ody fragments against digo'in, trade names igi$ind and igifa$%?.1/

Co'icity can also $e treated @ith higher than normal doses ofpotassium? igo'in is not

removed $y hemodialysis or peritoneal dialysis @ith enough effectiveness to treatto'icity?

igo'in has potentially dangerous interactions @ith verapamil,.1!/amiodarone,

erythromycin, and epinephrine(as @ould $e inEected @ith a local anesthetic%?

Actions

Chis section does not citeany reerences or sources? )*pril +,+
http://en.wikipedia.org/wiki/Anorexia_(symptom)http://en.wikipedia.org/wiki/Nauseahttp://en.wikipedia.org/wiki/Nauseahttp://en.wikipedia.org/wiki/Vomitinghttp://en.wikipedia.org/wiki/Diarrheahttp://en.wikipedia.org/wiki/Diarrheahttp://en.wikipedia.org/wiki/Blurred_visionhttp://en.wikipedia.org/wiki/Confusionhttp://en.wikipedia.org/wiki/Confusionhttp://en.wikipedia.org/wiki/Drowsinesshttp://en.wikipedia.org/wiki/Dizzinesshttp://en.wikipedia.org/wiki/Dizzinesshttp://en.wikipedia.org/wiki/Insomniahttp://en.wikipedia.org/wiki/Insomniahttp://en.wikipedia.org/wiki/Nightmarehttp://en.wikipedia.org/wiki/Nightmarehttp://en.wikipedia.org/wiki/Psychomotor_agitationhttp://en.wikipedia.org/wiki/Depression_(mood)http://en.wikipedia.org/wiki/Depression_(mood)http://en.wikipedia.org/wiki/Digoxin#cite_note-7http://en.wikipedia.org/wiki/Digoxin#cite_note-7http://en.wikipedia.org/wiki/Psychosishttp://en.wikipedia.org/wiki/Deliriumhttp://en.wikipedia.org/wiki/Deliriumhttp://en.wikipedia.org/wiki/Deliriumhttp://en.wikipedia.org/wiki/Amnesiahttp://en.wikipedia.org/wiki/Convulsionhttp://en.wikipedia.org/wiki/Convulsionhttp://en.wikipedia.org/wiki/Extrasystolehttp://en.wikipedia.org/wiki/Atrial_tachycardiahttp://en.wikipedia.org/wiki/AV_blockhttp://en.wikipedia.org/wiki/AV_blockhttp://en.wikipedia.org/wiki/Digoxin#cite_note-Rossi-6http://en.wikipedia.org/wiki/Digoxin#cite_note-Rossi-6http://en.wikipedia.org/wiki/Thrombocytopeniahttp://en.wikipedia.org/wiki/Thrombocytopeniahttp://en.wikipedia.org/wiki/Gynaecomastiahttp://en.wikipedia.org/wiki/Gynaecomastiahttp://en.wikipedia.org/wiki/Digoxin#cite_note-Moscovitz-8http://en.wikipedia.org/wiki/Digoxin#cite_note-9http://en.wikipedia.org/wiki/Electrocardiogramhttp://en.wikipedia.org/wiki/Electrocardiogramhttp://en.wikipedia.org/wiki/Bigeminyhttp://en.wikipedia.org/wiki/Ventricular_tachycardiahttp://en.wikipedia.org/wiki/Ventricular_tachycardiahttp://en.wikipedia.org/wiki/Fibrillationhttp://en.wikipedia.org/wiki/Pathognomonichttp://en.wikipedia.org/wiki/Digoxin#cite_note-Doering1977-10http://en.wikipedia.org/wiki/Xanthopsiahttp://en.wikipedia.org/wiki/Xanthopsiahttp://en.wikipedia.org/wiki/Vincent_van_Goghhttp://en.wikipedia.org/wiki/Vincent_van_Goghhttp://en.wikipedia.org/wiki/Digoxin#cite_note-11http://en.wikipedia.org/wiki/Digoxin#cite_note-11http://en.wikipedia.org/wiki/Starry_Nighthttp://en.wikipedia.org/wiki/Starry_Nighthttp://en.wikipedia.org/wiki/Foxglove_planthttp://en.wikipedia.org/wiki/Foxglove_planthttp://en.wikipedia.org/wiki/File:Portrait_of_Dr._Gachet.jpghttp://en.wikipedia.org/wiki/Antimalarialhttp://en.wikipedia.org/wiki/Antimalarialhttp://en.wikipedia.org/wiki/Hydroxychloroquinehttp://en.wikipedia.org/wiki/Hydroxychloroquinehttp://en.wikipedia.org/wiki/Digoxin#cite_note-12http://en.wikipedia.org/wiki/Digoxin#cite_note-Flanagan2004-13http://en.wikipedia.org/wiki/Digoxin#cite_note-Flanagan2004-13http://en.wikipedia.org/wiki/Digoxin#cite_note-Flanagan2004-13http://en.wikipedia.org/wiki/Potassiumhttp://en.wikipedia.org/wiki/Verapamilhttp://en.wikipedia.org/wiki/Verapamilhttp://en.wikipedia.org/wiki/Digoxin#cite_note-Kaplanski1983-14http://en.wikipedia.org/wiki/Amiodaronehttp://en.wikipedia.org/wiki/Erythromycinhttp://en.wikipedia.org/wiki/Epinephrinehttp://en.wikipedia.org/wiki/Wikipedia:Citing_sourceshttp://en.wikipedia.org/wiki/Wikipedia:Verifiabilityhttp://en.wikipedia.org/w/index.php?title=File:Question_book-new.svg&page=1http://en.wikipedia.org/wiki/Anorexia_(symptom)http://en.wikipedia.org/wiki/Nauseahttp://en.wikipedia.org/wiki/Vomitinghttp://en.wikipedia.org/wiki/Diarrheahttp://en.wikipedia.org/wiki/Blurred_visionhttp://en.wikipedia.org/wiki/Confusionhttp://en.wikipedia.org/wiki/Drowsinesshttp://en.wikipedia.org/wiki/Dizzinesshttp://en.wikipedia.org/wiki/Insomniahttp://en.wikipedia.org/wiki/Nightmarehttp://en.wikipedia.org/wiki/Psychomotor_agitationhttp://en.wikipedia.org/wiki/Depression_(mood)http://en.wikipedia.org/wiki/Digoxin#cite_note-7http://en.wikipedia.org/wiki/Psychosishttp://en.wikipedia.org/wiki/Deliriumhttp://en.wikipedia.org/wiki/Amnesiahttp://en.wikipedia.org/wiki/Convulsionhttp://en.wikipedia.org/wiki/Extrasystolehttp://en.wikipedia.org/wiki/Atrial_tachycardiahttp://en.wikipedia.org/wiki/AV_blockhttp://en.wikipedia.org/wiki/Digoxin#cite_note-Rossi-6http://en.wikipedia.org/wiki/Thrombocytopeniahttp://en.wikipedia.org/wiki/Gynaecomastiahttp://en.wikipedia.org/wiki/Digoxin#cite_note-Moscovitz-8http://en.wikipedia.org/wiki/Digoxin#cite_note-9http://en.wikipedia.org/wiki/Electrocardiogramhttp://en.wikipedia.org/wiki/Bigeminyhttp://en.wikipedia.org/wiki/Ventricular_tachycardiahttp://en.wikipedia.org/wiki/Fibrillationhttp://en.wikipedia.org/wiki/Pathognomonichttp://en.wikipedia.org/wiki/Digoxin#cite_note-Doering1977-10http://en.wikipedia.org/wiki/Xanthopsiahttp://en.wikipedia.org/wiki/Vincent_van_Goghhttp://en.wikipedia.org/wiki/Digoxin#cite_note-11http://en.wikipedia.org/wiki/Starry_Nighthttp://en.wikipedia.org/wiki/Foxglove_planthttp://en.wikipedia.org/wiki/File:Portrait_of_Dr._Gachet.jpghttp://en.wikipedia.org/wiki/Antimalarialhttp://en.wikipedia.org/wiki/Hydroxychloroquinehttp://en.wikipedia.org/wiki/Digoxin#cite_note-12http://en.wikipedia.org/wiki/Digoxin#cite_note-Flanagan2004-13http://en.wikipedia.org/wiki/Potassiumhttp://en.wikipedia.org/wiki/Verapamilhttp://en.wikipedia.org/wiki/Digoxin#cite_note-Kaplanski1983-14http://en.wikipedia.org/wiki/Amiodaronehttp://en.wikipedia.org/wiki/Erythromycinhttp://en.wikipedia.org/wiki/Epinephrinehttp://en.wikipedia.org/wiki/Wikipedia:Citing_sourceshttp://en.wikipedia.org/wiki/Wikipedia:Verifiability


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Che main pharmacological effects of digo'in are on theheart? >'tracardiac effects are

responsi$le for some of the therapeutic and many of the adverse effects (see $elo@%? ;t

has mechanical effects as it increases myocardialcontractility ho@ever, the duration ofthe contractile response is Eust slightly increased? Averall, the heart rate is decreased,

@hile$lood pressureincreases as the stroke volume is increased, leading to increased

tissueperfusion? 8yocardial efficiency is due to improved hemodynamics,and theventricular function curve is improved?

Ather, electrical effects are an initial $rief increase inaction potential, follo@ed $y a

decrease as the X conductance increases due to an increased intracellularamounts of

a*X ions? Che refractory periodof the atriaand ventriclesis decreased, @hile it increasesin the sinoatrialand 2V nodes? 2 less negative resting mem$rane potential is made,

leading to increased e'cita$ility? Ather, more indirect effects are cholinomimetic$ecause

of vagalstimulation, giving rise to 2V nodaldelay?

Che conduction velocity increases in the atria, $ut decreases in the 2V node? Che effect

upon 4urkinEe fi$ersand ventricles is negligi$le? 2utomaticity is also increased, in theatria, 2V node, 4urkinEe fi$ers and ventricles?

>Gchanges are increased 4R interval, due to decreased 2V conduction, and a

decreased =C interval $ecause of the altered duration of decreased action potential? 2lso,the C @ave is inverted, accompanied $y "C depression? ;t may cause 2V Eunctional

rhythm and ectopic $eats($igeminy% resulting in ventricular tachycardiaandfi$rillation?

"light vasodilationis seen in heart failure?Chis effect is contrary to effects that should $eseen as a result of increased intracellular calcium levels, $ut this occurs since digo'in

improves hemodynamics, @hich leads to restored angiotensinlevels and decreased

sympatheticdischarge, causing indirect vasodilation?

igo'in also affects the kidney$y increased renal $lood flo@ and increased glomerularfiltration rate? 2 mild diureticeffect is seen only in heart failure?

Mec%anism o action

Che mechanism of action is not completely understood ho@ever, the current hypothesis

is outlined $elo@?

igo'in $inds to a site on the e'tracellular aspect of the I&su$unit of theMaX5X 2C4ase

pump in the mem$ranesof heart cells (myocytes% and decreases its function? Chis causesan increase in the level of sodiumionsin the myocytes, @hich leads to a rise in the level

of intracellular calciumions? Chis occurs $ecause the sodium5calcium e'changer on theplasma mem$rane depends on a constant in@ard sodium gradient to pump out calcium?

igo'in decreases the sodium concentration gradient and the su$seNuent calcium

outflo@, thus raising the calcium concentration in myocardiocytes and pacemaker cells?
http://en.wikipedia.org/wiki/Hearthttp://en.wikipedia.org/wiki/Hearthttp://en.wikipedia.org/wiki/Myocardiumhttp://en.wikipedia.org/wiki/Myocardiumhttp://en.wikipedia.org/wiki/Blood_pressurehttp://en.wikipedia.org/wiki/Perfusionhttp://en.wikipedia.org/wiki/Hemodynamicshttp://en.wikipedia.org/wiki/Hemodynamicshttp://en.wikipedia.org/wiki/Action_potentialhttp://en.wikipedia.org/wiki/Action_potentialhttp://en.wikipedia.org/wiki/Potassiumhttp://en.wikipedia.org/wiki/Potassiumhttp://en.wikipedia.org/wiki/Potassiumhttp://en.wikipedia.org/wiki/Intracellularhttp://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Refractory_period_(physiology)http://en.wikipedia.org/wiki/Atrium_(heart)http://en.wikipedia.org/wiki/Atrium_(heart)http://en.wikipedia.org/wiki/Ventricle_(heart)http://en.wikipedia.org/wiki/Ventricle_(heart)http://en.wikipedia.org/wiki/Sinoatrial_nodehttp://en.wikipedia.org/wiki/Cholinergichttp://en.wikipedia.org/wiki/Vagus_nervehttp://en.wikipedia.org/wiki/AV_nodehttp://en.wikipedia.org/wiki/AV_nodehttp://en.wikipedia.org/wiki/Purkinje_fiberhttp://en.wikipedia.org/wiki/ECGhttp://en.wikipedia.org/wiki/Ectopic_beathttp://en.wikipedia.org/wiki/Ectopic_beathttp://en.wikipedia.org/wiki/Ventricular_tachycardiahttp://en.wikipedia.org/wiki/Ventricular_tachycardiahttp://en.wikipedia.org/wiki/Ventricular_fibrillationhttp://en.wikipedia.org/wiki/Ventricular_fibrillationhttp://en.wikipedia.org/wiki/Vasodilationhttp://en.wikipedia.org/wiki/Heart_failurehttp://en.wikipedia.org/wiki/Heart_failurehttp://en.wikipedia.org/wiki/Angiotensinhttp://en.wikipedia.org/wiki/Sympathetic_nervous_systemhttp://en.wikipedia.org/wiki/Kidneyhttp://en.wikipedia.org/wiki/Glomerular_filtration_ratehttp://en.wikipedia.org/wiki/Glomerular_filtration_ratehttp://en.wikipedia.org/wiki/Diuretichttp://en.wikipedia.org/wiki/Diuretichttp://en.wikipedia.org/wiki/NaKATPasehttp://en.wikipedia.org/wiki/NaKATPasehttp://en.wikipedia.org/wiki/NaKATPasehttp://en.wikipedia.org/wiki/NaKATPasehttp://en.wikipedia.org/wiki/NaKATPasehttp://en.wikipedia.org/wiki/Cell_membranehttp://en.wikipedia.org/wiki/Sodiumhttp://en.wikipedia.org/wiki/Sodiumhttp://en.wikipedia.org/wiki/Ionhttp://en.wikipedia.org/wiki/Ionhttp://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Hearthttp://en.wikipedia.org/wiki/Myocardiumhttp://en.wikipedia.org/wiki/Blood_pressurehttp://en.wikipedia.org/wiki/Perfusionhttp://en.wikipedia.org/wiki/Hemodynamicshttp://en.wikipedia.org/wiki/Action_potentialhttp://en.wikipedia.org/wiki/Potassiumhttp://en.wikipedia.org/wiki/Intracellularhttp://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Refractory_period_(physiology)http://en.wikipedia.org/wiki/Atrium_(heart)http://en.wikipedia.org/wiki/Ventricle_(heart)http://en.wikipedia.org/wiki/Sinoatrial_nodehttp://en.wikipedia.org/wiki/Cholinergichttp://en.wikipedia.org/wiki/Vagus_nervehttp://en.wikipedia.org/wiki/AV_nodehttp://en.wikipedia.org/wiki/Purkinje_fiberhttp://en.wikipedia.org/wiki/ECGhttp://en.wikipedia.org/wiki/Ectopic_beathttp://en.wikipedia.org/wiki/Ventricular_tachycardiahttp://en.wikipedia.org/wiki/Ventricular_fibrillationhttp://en.wikipedia.org/wiki/Vasodilationhttp://en.wikipedia.org/wiki/Heart_failurehttp://en.wikipedia.org/wiki/Angiotensinhttp://en.wikipedia.org/wiki/Sympathetic_nervous_systemhttp://en.wikipedia.org/wiki/Kidneyhttp://en.wikipedia.org/wiki/Glomerular_filtration_ratehttp://en.wikipedia.org/wiki/Glomerular_filtration_ratehttp://en.wikipedia.org/wiki/Diuretichttp://en.wikipedia.org/wiki/NaKATPasehttp://en.wikipedia.org/wiki/Cell_membranehttp://en.wikipedia.org/wiki/Sodiumhttp://en.wikipedia.org/wiki/Ionhttp://en.wikipedia.org/wiki/Calcium


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;ncreased intracellular calcium lengthens phase and phase # of thecardiac action

potential, @hich leads to a decrease in heart rate?.1+/;ncreased amounts of a*Xalso leads

to increased storage of calcium in the sarcoplasmic reticulum, causing a correspondingincrease in the release of calcium during each action potential? Chis leads to increased

contractility (the force of contraction% of the heart @ithout increasing heart energy

e'penditure?

Chere is also evidence that digo'in increasesvagalactivity, there$y decreasing heart rate$y slo@ing depolari0ation of pacemaker cells in the2V node?.1)/Chis negative

chronotropic effect @ould therefore $e synergistic @ith the direct effect on cardiac

pacemaker cells? igo'in is used @idely in the treatment of variousarrhythmias?

Society and culture

harles ullenadmitted in *##3 to killing as many as # hospital patients @ith overdoses

of heart medicationZusually digo'inZat hospitals in Me@ Jersey and 4ennsylvania over

his 1+&year career as a nurse? An 8arch 1#, *##+, he @as sentenced to 1 consecutive lifesentences and is not eligi$le for parole?.1/

An 2pril *!, *##, the F2 issued a press release .1/alerting the pu$lic to a lass ; recall

of igitek, a $rand of digo'in produced $y 8ylan?.*#/"ome ta$lets had $een released at

dou$le thickness and therefore dou$le strength, causing some patients to e'periencedigo'in to'icity? 2 class&action la@suit against the ;celandic generic drug maker 2ctavis

@as announced t@o @eeks later?.*1/

An 8arch 31, *##, the F2 announced another generic digo'in pill recall $y postingthis company press release on the agencyDs @e$ site: Baraco 4harmaceutical

9a$oratories, 9td? 2nnounces a Mation@ide Voluntary Recall of 2ll 9ots of igo'inCa$lets ue to "i0e Varia$ilityB?

Chis 8arch 31 press release from araco, a generic pharmaceutical company, states:

.2ll/ ta$lets of araco $rand igo'in, "4, #?1*! mg, and igo'in, "4, #?*! mg,distri$uted prior to 8arch 31, *##, @hich are not e'pired and are @ithin the e'piration

date of "eptem$er, *#11, are $eing voluntarily recalled to the consumer level? Che ta$lets

are $eing recalled $ecause they may differ in si0e and therefore could have more or lessof the active ingredient, digo'in?

2 *## study suggested digo'in has $eneficial effects not only for the heart, $ut also inreducing the risk of certain kinds of cancer?.**/-o@ever, comments on this study

suggested that digo'in is not effective at reducing cancer risk at therapeuticconcentrations of the drug,.*3/so the results need further investigation?.*/
http://en.wikipedia.org/wiki/Cardiac_action_potentialhttp://en.wikipedia.org/wiki/Cardiac_action_potentialhttp://en.wikipedia.org/wiki/Cardiac_action_potentialhttp://en.wikipedia.org/wiki/Digoxin#cite_note-15http://en.wikipedia.org/wiki/Sarcoplasmic_reticulumhttp://en.wikipedia.org/wiki/Vagalhttp://en.wikipedia.org/wiki/Vagalhttp://en.wikipedia.org/wiki/AV_nodehttp://en.wikipedia.org/wiki/AV_nodehttp://en.wikipedia.org/wiki/AV_nodehttp://en.wikipedia.org/wiki/Digoxin#cite_note-16http://en.wikipedia.org/wiki/Arrhythmiahttp://en.wikipedia.org/wiki/Arrhythmiahttp://en.wikipedia.org/wiki/Charles_Cullenhttp://en.wikipedia.org/wiki/Digoxin#cite_note-17http://en.wikipedia.org/wiki/Digoxin#cite_note-17http://en.wikipedia.org/wiki/Digoxin#cite_note-18http://en.wikipedia.org/wiki/Digoxin#cite_note-19http://en.wikipedia.org/wiki/Digoxin#cite_note-20http://en.wikipedia.org/wiki/Digoxin#cite_note-21http://en.wikipedia.org/wiki/Digoxin#cite_note-21http://en.wikipedia.org/wiki/Digoxin#cite_note-21http://en.wikipedia.org/wiki/Digoxin#cite_note-22http://en.wikipedia.org/wiki/Digoxin#cite_note-22http://en.wikipedia.org/wiki/Digoxin#cite_note-23http://en.wikipedia.org/wiki/Cardiac_action_potentialhttp://en.wikipedia.org/wiki/Cardiac_action_potentialhttp://en.wikipedia.org/wiki/Digoxin#cite_note-15http://en.wikipedia.org/wiki/Sarcoplasmic_reticulumhttp://en.wikipedia.org/wiki/Vagalhttp://en.wikipedia.org/wiki/AV_nodehttp://en.wikipedia.org/wiki/Digoxin#cite_note-16http://en.wikipedia.org/wiki/Arrhythmiahttp://en.wikipedia.org/wiki/Charles_Cullenhttp://en.wikipedia.org/wiki/Digoxin#cite_note-17http://en.wikipedia.org/wiki/Digoxin#cite_note-18http://en.wikipedia.org/wiki/Digoxin#cite_note-19http://en.wikipedia.org/wiki/Digoxin#cite_note-20http://en.wikipedia.org/wiki/Digoxin#cite_note-21http://en.wikipedia.org/wiki/Digoxin#cite_note-22http://en.wikipedia.org/wiki/Digoxin#cite_note-23


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Cam,tot%ecinFrom Wikipedia, the free encyclopedia

Jump to: navigation,search

amptothecin

Systematic (IUPAC) name(S%&&ethyl&&hydro'y&1'&pyrano.3D,D:+,)/indoli0ino.1,*&$/

Nuinoline&3,1&(',1*'%&dione

Clinical data

Pregnancy cat. [

egal status [

Identiiers
http://en.wikipedia.org/wiki/Camptothecin#mw-headhttp://en.wikipedia.org/wiki/Camptothecin#mw-headhttp://en.wikipedia.org/wiki/Camptothecin#p-searchhttp://en.wikipedia.org/wiki/International_Union_of_Pure_and_Applied_Chemistry_nomenclaturehttp://en.wikipedia.org/wiki/Pregnancy_categoryhttp://en.wikipedia.org/wiki/Regulation_of_therapeutic_goodshttp://en.wikipedia.org/wiki/File:Camptothecin.pnghttp://en.wikipedia.org/wiki/Camptothecin#mw-headhttp://en.wikipedia.org/wiki/Camptothecin#p-searchhttp://en.wikipedia.org/wiki/International_Union_of_Pure_and_Applied_Chemistry_nomenclaturehttp://en.wikipedia.org/wiki/Pregnancy_categoryhttp://en.wikipedia.org/wiki/Regulation_of_therapeutic_goods


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CAS numer )+&

A+C code Mone

PuC%em ; *!3

Drug'an& 8&ring modifications

! 4C analogues

+ References
http://en.wikipedia.org/wiki/CAS_registry_numberhttp://www.nlm.nih.gov/cgi/mesh/2009/MB_cgi?term=7689-03-4&rn=1http://www.nlm.nih.gov/cgi/mesh/2009/MB_cgi?term=7689-03-4&rn=1http://en.wikipedia.org/wiki/Anatomical_Therapeutic_Chemical_Classification_Systemhttp://en.wikipedia.org/wiki/PubChemhttp://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2538http://en.wikipedia.org/wiki/DrugBankhttp://www.drugbank.ca/drugs/DB04690http://en.wikipedia.org/wiki/ChemSpiderhttp://www.chemspider.com/Chemical-Structure.22775http://www.chemspider.com/Chemical-Structure.22775http://en.wikipedia.org/wiki/Unique_Ingredient_Identifierhttp://fdasis.nlm.nih.gov/srs/srsdirect.jsp?regno=XT3Z54Z28Ahttp://fdasis.nlm.nih.gov/srs/srsdirect.jsp?regno=XT3Z54Z28Ahttp://en.wikipedia.org/wiki/KEGGhttp://www.kegg.jp/entry/C01897http://www.kegg.jp/entry/C01897http://en.wikipedia.org/wiki/ChEBIhttps://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:27656https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:27656http://en.wikipedia.org/wiki/ChEMBLhttps://www.ebi.ac.uk/chembldb/index.php/compound/inspect/CHEMBL65https://www.ebi.ac.uk/chembldb/index.php/compound/inspect/CHEMBL65http://en.wikipedia.org/wiki/Chemical_formulahttp://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Oxygenhttp://en.wikipedia.org/wiki/Molecular_masshttp://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specificationhttp://en.wikipedia.org/wiki/International_Chemical_Identifierhttp://en.wikipedia.org/wiki/Wikipedia:WikiProject_Chemicals/Chembox_validationhttp://en.wikipedia.org/w/index.php?title=Special:ComparePages&rev1=443672460&page2=Camptothecinhttp://en.wikipedia.org/wiki/Cytotoxichttp://en.wikipedia.org/wiki/Quinolinehttp://en.wikipedia.org/wiki/Alkaloidhttp://en.wikipedia.org/wiki/Enzyme_inhibitorhttp://en.wikipedia.org/wiki/DNAhttp://en.wikipedia.org/wiki/Enzymehttp://en.wikipedia.org/wiki/Topoisomerase_Ihttp://en.wikipedia.org/wiki/Topoisomerase_Ihttp://en.wiktionary.org/wiki/screeninghttp://en.wikipedia.org/wiki/Natural_productshttp://en.wikipedia.org/wiki/Natural_productshttp://en.wikipedia.org/wiki/Drugshttp://en.wikipedia.org/wiki/Drugshttp://en.wikipedia.org/wiki/Drugshttp://en.wikipedia.org/wiki/Barkhttp://en.wikipedia.org/wiki/Plant_stemhttp://en.wikipedia.org/wiki/Camptotheca_acuminatahttp://en.wikipedia.org/wiki/Treehttp://en.wikipedia.org/wiki/Treehttp://en.wikipedia.org/wiki/Chinahttp://en.wikipedia.org/wiki/Traditional_Chinese_Medicinehttp://en.wikipedia.org/wiki/Traditional_Chinese_Medicinehttp://en.wikipedia.org/wiki/Camptothecin#cite_note-0http://en.wikipedia.org/wiki/Camptothecin#cite_note-0http://en.wikipedia.org/wiki/Clinical_trialshttp://en.wikipedia.org/wiki/Clinical_trialshttp://en.wikipedia.org/wiki/Solubilityhttp://en.wikipedia.org/wiki/Solubilityhttp://en.wikipedia.org/wiki/Adverse_drug_reactionhttp://en.wikipedia.org/wiki/Camptothecin#cite_note-1http://en.wikipedia.org/wiki/Camptothecin#cite_note-2http://en.wikipedia.org/wiki/Camptothecin#cite_note-3http://en.wikipedia.org/wiki/Chemicalhttp://en.wikipedia.org/wiki/Chemicalhttp://en.wikipedia.org/wiki/Analog_(chemistry)http://en.wikipedia.org/wiki/Cancerhttp://en.wikipedia.org/wiki/Chemotherapyhttp://en.wikipedia.org/wiki/Chemotherapyhttp://en.wikipedia.org/wiki/Chemotherapyhttp://en.wikipedia.org/wiki/Camptothecin#cite_note-4http://en.wikipedia.org/wiki/Camptothecin#cite_note-4http://en.wikipedia.org/wiki/Topotecanhttp://en.wikipedia.org/wiki/Irinotecanhttp://en.wikipedia.org/wiki/Camptothecin#cite_note-M.E._Wall_1966-5http://en.wikipedia.org/wiki/Camptothecin#cite_note-M.E._Wall_1966-5http://en.wikipedia.org/wiki/Camptothecin#cite_note-G._Samuelsson_2004-6http://en.wikipedia.org/wiki/Camptothecin#Structureshttp://en.wikipedia.org/wiki/Camptothecin#Bindinghttp://en.wikipedia.org/wiki/Camptothecin#Physical_and_chemical_propertieshttp://en.wikipedia.org/wiki/Camptothecin#SAR_.E2.80.93_Structure-activity_relationshiphttp://en.wikipedia.org/wiki/Camptothecin#A-_and_B-ring_modificationhttp://en.wikipedia.org/wiki/Camptothecin#Alkyl_substitutionhttp://en.wikipedia.org/wiki/Camptothecin#Hexacyclic_CPT_analogueshttp://en.wikipedia.org/wiki/Camptothecin#C-_and_D-ring_modificationhttp://en.wikipedia.org/wiki/Camptothecin#E-ring_modificationshttp://en.wikipedia.org/wiki/Camptothecin#CPT_analogueshttp://en.wikipedia.org/wiki/Camptothecin#Referenceshttp://en.wikipedia.org/wiki/CAS_registry_numberhttp://www.nlm.nih.gov/cgi/mesh/2009/MB_cgi?term=7689-03-4&rn=1http://en.wikipedia.org/wiki/Anatomical_Therapeutic_Chemical_Classification_Systemhttp://en.wikipedia.org/wiki/PubChemhttp://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2538http://en.wikipedia.org/wiki/DrugBankhttp://www.drugbank.ca/drugs/DB04690http://en.wikipedia.org/wiki/ChemSpiderhttp://www.chemspider.com/Chemical-Structure.22775http://en.wikipedia.org/wiki/Unique_Ingredient_Identifierhttp://fdasis.nlm.nih.gov/srs/srsdirect.jsp?regno=XT3Z54Z28Ahttp://en.wikipedia.org/wiki/KEGGhttp://www.kegg.jp/entry/C01897http://en.wikipedia.org/wiki/ChEBIhttps://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:27656http://en.wikipedia.org/wiki/ChEMBLhttps://www.ebi.ac.uk/chembldb/index.php/compound/inspect/CHEMBL65http://en.wikipedia.org/wiki/Chemical_formulahttp://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Oxygenhttp://en.wikipedia.org/wiki/Molecular_masshttp://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specificationhttp://en.wikipedia.org/wiki/International_Chemical_Identifierhttp://en.wikipedia.org/wiki/Wikipedia:WikiProject_Chemicals/Chembox_validationhttp://en.wikipedia.org/w/index.php?title=Special:ComparePages&rev1=443672460&page2=Camptothecinhttp://en.wikipedia.org/wiki/Cytotoxichttp://en.wikipedia.org/wiki/Quinolinehttp://en.wikipedia.org/wiki/Alkaloidhttp://en.wikipedia.org/wiki/Enzyme_inhibitorhttp://en.wikipedia.org/wiki/DNAhttp://en.wikipedia.org/wiki/Enzymehttp://en.wikipedia.org/wiki/Topoisomerase_Ihttp://en.wiktionary.org/wiki/screeninghttp://en.wikipedia.org/wiki/Natural_productshttp://en.wikipedia.org/wiki/Drugshttp://en.wikipedia.org/wiki/Barkhttp://en.wikipedia.org/wiki/Plant_stemhttp://en.wikipedia.org/wiki/Camptotheca_acuminatahttp://en.wikipedia.org/wiki/Treehttp://en.wikipedia.org/wiki/Chinahttp://en.wikipedia.org/wiki/Traditional_Chinese_Medicinehttp://en.wikipedia.org/wiki/Camptothecin#cite_note-0http://en.wikipedia.org/wiki/Clinical_trialshttp://en.wikipedia.org/wiki/Solubilityhttp://en.wikipedia.org/wiki/Adverse_drug_reactionhttp://en.wikipedia.org/wiki/Camptothecin#cite_note-1http://en.wikipedia.org/wiki/Camptothecin#cite_note-2http://en.wikipedia.org/wiki/Camptothecin#cite_note-3http://en.wikipedia.org/wiki/Chemicalhttp://en.wikipedia.org/wiki/Analog_(chemistry)http://en.wikipedia.org/wiki/Cancerhttp://en.wikipedia.org/wiki/Chemotherapyhttp://en.wikipedia.org/wiki/Camptothecin#cite_note-4http://en.wikipedia.org/wiki/Topotecanhttp://en.wikipedia.org/wiki/Irinotecanhttp://en.wikipedia.org/wiki/Camptothecin#cite_note-M.E._Wall_1966-5http://en.wikipedia.org/wiki/Camptothecin#cite_note-G._Samuelsson_2004-6http://en.wikipedia.org/wiki/Camptothecin#Structureshttp://en.wikipedia.org/wiki/Camptothecin#Bindinghttp://en.wikipedia.org/wiki/Camptothecin#Physical_and_chemical_propertieshttp://en.wikipedia.org/wiki/Camptothecin#SAR_.E2.80.93_Structure-activity_relationshiphttp://en.wikipedia.org/wiki/Camptothecin#A-_and_B-ring_modificationhttp://en.wikipedia.org/wiki/Camptothecin#Alkyl_substitutionhttp://en.wikipedia.org/wiki/Camptothecin#Hexacyclic_CPT_analogueshttp://en.wikipedia.org/wiki/Camptothecin#C-_and_D-ring_modificationhttp://en.wikipedia.org/wiki/Camptothecin#E-ring_modificationshttp://en.wikipedia.org/wiki/Camptothecin#CPT_analogueshttp://en.wikipedia.org/wiki/Camptothecin#References


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Structures

4C has a planar pentacyclic ring structure,that includes apyrrolo.3,&H/&Nuinoline

moiety (rings 2, < and %, conEugatedpyridonemoiety (ring % and onechiralcenter atposition *# @ithin the alpha&hydro'y lactonering @ith ("% configuration(the >&ring%? ;ts

planar structure is thought to $e one of the most important factors in topoisomeraseinhi$ition?././

&ring @hich interacts

from three different positions @ith the en0yme? Che hydro'yl group in position *# forms

hydrogen $ond to the side chain on aspartic acidnum$er !33(2sp!33% in the en0yme?;tOs critical that the configurationof the chiralcar$onis ("% $ecause (R% is inactive? Che

lactone is $onded @ith t@o hydrogen $onds to the aminogroups on arginine3+

(2rg3+%? Che &ring interacts @ith the X1 cytosineon non&cleaved strand and sta$ili0es

the topo ;&M2 covalent comple' $y forming hydrogen $ond? Chis hydrogen $ond is$et@een car$onylgroup in position 1) on the &ring and amino group on thepyrimidine

ring of X1 cytosine?.1#/.11/Co'icity of 4C is primarily a result of conversion of single&

strand $reaks into dou$le&strand $reaks during the "&phase @hen the replication forkcollides @ith the cleavage comple'es formed $y M2 and 4C?.1*/

P%ysical and c%emical ,ro,erties
http://en.wikipedia.org/wiki/Structurehttp://en.wikipedia.org/wiki/Structurehttp://en.wikipedia.org/wiki/Pyrrolehttp://en.wikipedia.org/wiki/Pyrrolehttp://en.wikipedia.org/wiki/Conjugated_systemhttp://en.wikipedia.org/wiki/Pyridonehttp://en.wikipedia.org/wiki/Chirality_(chemistry)http://en.wikipedia.org/wiki/Chirality_(chemistry)http://en.wikipedia.org/wiki/Alpha_carbonhttp://en.wikipedia.org/wiki/Hydroxylhttp://en.wikipedia.org/wiki/Lactonehttp://en.wikipedia.org/wiki/Chirality_(chemistry)http://en.wikipedia.org/wiki/Camptothecin#cite_note-H._Ulukan_2002-7http://en.wikipedia.org/wiki/Camptothecin#cite_note-A.J._Lu_2002-8http://en.wikipedia.org/wiki/Apoptosishttp://en.wikipedia.org/wiki/Hydrogen_bondshttp://en.wikipedia.org/wiki/Aspartic_acidhttp://en.wikipedia.org/wiki/Peptide_sequencehttp://en.wikipedia.org/wiki/Configurationhttp://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Aminohttp://en.wikipedia.org/wiki/Aminohttp://en.wikipedia.org/wiki/Argininehttp://en.wikipedia.org/wiki/Argininehttp://en.wikipedia.org/wiki/Cytosinehttp://en.wikipedia.org/wiki/Carbonylhttp://en.wikipedia.org/wiki/Pyrimidinehttp://en.wikipedia.org/wiki/Pyrimidinehttp://en.wikipedia.org/wiki/Camptothecin#cite_note-D.J.Adams_2005-9http://en.wikipedia.org/wiki/Camptothecin#cite_note-M.R.Redinbo_1998-10http://en.wikipedia.org/wiki/Camptothecin#cite_note-M.R.Redinbo_1998-10http://en.wikipedia.org/wiki/Camptothecin#cite_note-Y.Pommier_2003-11http://en.wikipedia.org/wiki/Camptothecin#cite_note-Y.Pommier_2003-11http://en.wikipedia.org/wiki/File:Camptothecin_binding.svghttp://en.wikipedia.org/w/index.php?title=File:Camptothecin_binding.svg&page=1http://en.wikipedia.org/wiki/Structurehttp://en.wikipedia.org/wiki/Pyrrolehttp://en.wikipedia.org/wiki/Conjugated_systemhttp://en.wikipedia.org/wiki/Pyridonehttp://en.wikipedia.org/wiki/Chirality_(chemistry)http://en.wikipedia.org/wiki/Alpha_carbonhttp://en.wikipedia.org/wiki/Hydroxylhttp://en.wikipedia.org/wiki/Lactonehttp://en.wikipedia.org/wiki/Chirality_(chemistry)http://en.wikipedia.org/wiki/Camptothecin#cite_note-H._Ulukan_2002-7http://en.wikipedia.org/wiki/Camptothecin#cite_note-A.J._Lu_2002-8http://en.wikipedia.org/wiki/Apoptosishttp://en.wikipedia.org/wiki/Hydrogen_bondshttp://en.wikipedia.org/wiki/Aspartic_acidhttp://en.wikipedia.org/wiki/Peptide_sequencehttp://en.wikipedia.org/wiki/Configurationhttp://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Aminohttp://en.wikipedia.org/wiki/Argininehttp://en.wikipedia.org/wiki/Cytosinehttp://en.wikipedia.org/wiki/Carbonylhttp://en.wikipedia.org/wiki/Pyrimidinehttp://en.wikipedia.org/wiki/Camptothecin#cite_note-D.J.Adams_2005-9http://en.wikipedia.org/wiki/Camptothecin#cite_note-M.R.Redinbo_1998-10http://en.wikipedia.org/wiki/Camptothecin#cite_note-Y.Pommier_2003-11


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Che lactone ring in 4C is highly suscepti$le to hydrolysis?Che open ring form is

inactive and it must therefore $e closed to inhi$it topo ;? Che closed form is favored in

acidic condition, as it is in many cancer cellsmicroenvironment? 4C is transported in tothe cell $ypassive diffusion? ellular uptake is favored $y lipophilicity, @hich enhances

intracellularaccumulation? 9ipophilicity makes compoundsmore sta$le $ecause of

improved lactone partitioning into red $lood cellsand conseNuently less hydrolysis of thelactone? 4C has affinity for human serum al$umin (-"2%, especially the car$o'ylate

form of 4C? nlargement of the lactone ring $y one methyleneunit also enhances its a$ilities, as in

homocamptothecin? "u$stitution at position 1* and 1 leads to inactive derivative?.13/

A- and B-ring modification

Al&yl sustitution

2lkylsu$stitution at position ) has sho@n increased cytoto'icity, such asethyl(*-!% or

chloromethyl (-*l%? Chese groups are a$le to react @ith the M2 in the presence of

topo ; @hich leads to more tumoractivity? ;t has also $een sho@n that increasing thelength of the car$on chain (in position )% leads to increased lipophilicity and

conseNuently greater potency and sta$ility in humanplasma?.1#/.13/Ather )&modified 4C

analogues are silatecans and karenitecins? Chey are potent inihi$itors on topo ; and $othhave alkylsilyl groups in position ) @hich make them lipophilic and more sta$le?

"ilatecans or )&silylcampthothecins have sho@n reduced drug&-"2 interactions @hich

contri$utes to its $lood sta$ility and they can also cross the$lood $rain $arrier?


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compounds is the o'yiminomethyl derivative "C11 that has the advantage to overcome

drug resistance caused $y transport systems?.13/'atecan is an e'ample of he'acyclic 4C that has a + mem$ered

ring over position ) and , and is 1#&methyl, 11&fluoro su$stituted ./? ;t is @ater&solu$leand more potent than topotecan?./.13/.1!/

C- and D-ring modification

Che & and &rings have an essential role in the antitumor activity? Replacement in any

position results in much less potent compound than parent compound in othercytoto'icity assay?./
http://en.wikipedia.org/wiki/Camptothecin#cite_note-F._Zunino_2002-12http://en.wikipedia.org/wiki/Camptothecin#cite_note-F._Zunino_2002-12http://en.wikipedia.org/wiki/Camptothecin#cite_note-F._Zunino_2002-12http://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Hydrophilichttp://en.wikipedia.org/wiki/Camptothecin#cite_note-F._Zunino_2002-12http://en.wikipedia.org/wiki/Camptothecin#cite_note-M._K._Chung_2006-13http://en.wikipedia.org/wiki/Nitro_compoundhttp://en.wikipedia.org/wiki/Bromohttp://en.wikipedia.org/wiki/Chlorohttp://en.wikipedia.org/wiki/Methoxyhttp://en.wikipedia.org/wiki/Camptothecin#cite_note-H._Ulukan_2002-7http://en.wikipedia.org/wiki/Camptothecin#cite_note-F._Zunino_2002-12http://en.wikipedia.org/wiki/Methylenedioxyhttp://en.wikipedia.org/wiki/Camptothecin#cite_note-H._Ulukan_2002-7http://en.wikipedia.org/wiki/Camptothecin#cite_note-F._Zunino_2002-12http://en.wikipedia.org/wiki/Camptothecin#cite_note-H._Ulukan_2002-7http://en.wikipedia.org/wiki/Camptothecin#cite_note-H._Ulukan_2002-7http://en.wikipedia.org/wiki/Camptothecin#cite_note-F._Zunino_2002-12http://en.wikipedia.org/wiki/Camptothecin#cite_note-M._Palumbo_2001-14http://en.wikipedia.org/wiki/Camptothecin#cite_note-H._Ulukan_2002-7http://en.wikipedia.org/wiki/Camptothecin#cite_note-F._Zunino_2002-12http://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Hydrophilichttp://en.wikipedia.org/wiki/Camptotheci

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