TY  - CHAP
M1  - Book, Section
TI  - SILIBININ
A1  - Olson, Kent R.
A2  - Olson, Kent R.
A2  - Anderson, Ilene B.
A2  - Benowitz, Neal L.
A2  - Blanc, Paul D.
A2  - Clark, Richard F.
A2  - Kearney, Thomas E.
A2  - Kim-Katz, Susan Y.
A2  - Wu, Alan H. B.
PY  - 2018
T2  - Poisoning & Drug Overdose, 7e
AB  - Pharmacology.  Extracts  of  the  milk  thistle  plant  (Silybum  marianum)  have  been  used  since  ancient  times  to  treat  a  variety  of  hepatic  and  biliary  disorders,  including  cholestasis,  jaundice,  cirrhosis,  acute  and  chronic  hepatitis,  and  primary  malignancies,  and  to  protect  the  liver  against  toxin-induced  injury.  The  extract  of  the  ripe  seeds  and  leaves  contains  70-80%  silymarin,  a  flavanolignan  mixture  of  which  silibinin  is  the  most  biologically  active  constituent.  The  hypothesized  mechanism  of  action  is  twofold:  alteration  of  hepatocyte  cell  membrane  permeability,  preventing  toxin  penetration;  and  increased  ribosomal  protein  synthesis,  promoting  hepatocyte  regeneration.Although  the  efficacy  of  silibinin  has  not  been  established  in  controlled  studies  in  humans,  it  has  been  associated  with  reduced  liver  damage  when  administered  intravenously  in  the  treatment  of  amatoxin  mushroom  poisoning.  Competitive  inhibition  of  amatoxin  entry  via  the  membrane  transport  system  for  bile  salts  has  been  demonstrated.  Silibinin  also  appears  to  inhibit  tumor  necrosis  factor  (TNF)  release  in  the  injured  liver,  thus  slowing  the  process  of  amatoxin-induced  apoptosis.Silymarin  also  is  reported  to  have  antifibrotic,  anti-inflammatory,  and  antioxidant  activity  and  may  have  therapeutic  efficacy  in  the  treatment  of  prostate  and  skin  cancer.  There  is  preliminary  evidence  that  milk  thistle  constituents  may  also  protect  against  the  nephrotoxic  effects  of  drugs  such  as  acetaminophen,  cisplatin,  and  vincristine.IndicationsIntravenous  silibinin  is  approved  across  Europe  for  the  prevention  and  treatment  of  fulminant  hepatic  failure  following  ingestion  of  amatoxin-containing  mushrooms.  An  FDA-sanctioned  clinical  trial  has  made  the  drug  available  in  the  United  States  as  well.Although  this  indication  is  unproven,  silibinin  may  be  effective  as  adjuvant  therapy  in  cases  of  acute  hepatic  injury  caused  by  acetaminophen  toxicity  and  potentially  other  chemical-  and  drug-induced  liver  diseases.Contraindications.  None  reported.Adverse  effects  are  few  and  generally  mild.Nausea,  diarrhea,  abdominal  fullness  or  pain,  flatulence,  and  anorexia  may  occur  in  users  of  oral  preparations.Mild  warmth  and  a  flushing  sensation  are  commonly  reported  during  intravenous  infusion.Milk  thistle  is  a  member  of  the  Asteraceae  (daisy)  family  and  can  cause  an  allergic  reaction  in  ragweed-sensitive  individuals,  including  rash,  urticaria,  pruritus,  and  anaphylaxis.Use  in  pregnancy.  FDA  Category  B.  Insufficient  reliable  information  is  available  (Introduction).Drug  or  laboratory  interactions.  Although  milk  thistle  has  been  shown  to  induce  slight  cytochrome  P-450  enzyme  inhibition  in  vitro,  significant  drug  interactions  with  milk  thistle  extract  have  not  been  demonstrated  in  humans.Dosage  and  method  of  administrationIntravenous  dosing  for  amatoxin  mushroom  poisoning  is  20–50  mg/kg/d  by  continuous  infusion  or  in  four  divided  doses  administered  over  2  hours  each.Oral  doses  used  in  published  studies  have  ranged  from  280  to  800  mg/d  of  standardized  silymarin.  A  typical  dose  used  for  chronic  hepatitis  is  420  mg/d  in  two  or  three  oral  doses.FormulationsOral.  In  the  United  States,  milk  thistle  extracts  are  available  as  over-the-counter  dietary  supplements  (eg,  Thisilyn).  Oral  formulations  include  Legalon  (standardized  to  contain  70%  silibinin)  and  Silipide  (silibinin  complexed  with  phosphatidylcholine,  which  has  a  higher  oral  bioavailability).  Because  silymarin  is  poorly  water-soluble,  milk  thistle  tea  is  not  considered  an  effective  preparation.Parenteral.  Intravenous  silibinin  can  be  obtained  for  the  treatment  of  amatoxin  mushroom  poisoning  as  an  FDA-sanctioned  open  Investigational  New  Drug  (call  toll-free  1-866-520-4412).  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/23
UR  - accessmedicine.mhmedical.com/content.aspx?aid=1179993076
ER  -