RT Book, Section
A1 Kosnett, Michael J.
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.
SR Print(0)
ID 1179993079
T1 SUCCIMER (DMSA)
T2 Poisoning & Drug Overdose, 7e
YR 2018
FD 2018
PB McGraw-Hill Education
PP New York, NY
SN 9780071839792
LK accessmedicine.mhmedical.com/content.aspx?aid=1179993079
RD 2024/04/18
AB PharmacologySuccimer  (meso-2,3-dimercaptosuccinic  acid  [DMSA])  is  a  chelating  agent  that  is  used  in  the  treatment  of  intoxication  from  several  heavy  metals.  A  water-soluble  analog  of  BAL  (dimercaprol),  succimer  enhances  the  urinary  excretion  of  lead  and  mercury.  Its  effect  on  the  elimination  of  the  endogenous  minerals  calcium,  iron,  and  magnesium  is  insignificant.  Minor  increases  in  zinc  and  copper  excretion  may  occur.  In  an  animal  model,  oral  succimer  was  not  associated  with  a  significant  increase  in  the  GI  absorption  of  lead  or  inorganic  mercury  (as  mercuric  chloride);  the  effect  of  oral  succimer  on  the  GI  absorption  of  arsenic  is  not  known.After  oral  administration,  peak  blood  concentrations  occur  in  approximately  3  hours.  Distribution  is  predominantly  extracellular,  and  in  the  blood,  succimer  is  extensively  bound  (>90%)  to  plasma  proteins.  Succimer  is  eliminated  primarily  in  the  urine,  where  80-90%  appears  as  mixed  disulfides,  mainly  2:1  or  1:1  cysteine-succimer  adducts.  Studies  suggest  that  these  adducts,  rather  than  the  parent  drug,  may  be  responsible  for  metal-chelating  activity  in  vivo.  Renal  elimination  of  the  metal  chelates  appears  to  be  mediated  in  part  by  the  multidrug  resistance  protein  2  (Mrp2).  The  elimination  half-life  of  transformed  succimer  is  approximately  2–4  hours.  Renal  clearance  may  be  diminished  in  the  setting  of  pediatric  lead  intoxication.IndicationsSuccimer  is  approved  for  the  treatment  of  lead  intoxication,  where  it  is  associated  with  increased  urinary  excretion  of  the  metal  and  concurrent  reversal  of  metal-induced  enzyme  inhibition.  At  moderately  elevated  blood  lead  concentrations,  oral  succimer  is  comparable  with  parenteral  calcium  EDTA  in  decreasing  blood  lead  concentrations.  The  efficiency  of  succimer  in  eliminating  lead  from  the  blood  and  tissues  may  somewhat  decline  at  very  high  blood  concentrations  of  lead  (eg,  >100  mcg/dL).  Although  succimer  treatment  has  been  associated  with  subjective  clinical  improvement,  controlled  clinical  trials  demonstrating  therapeutic  efficacy  have  not  been  reported.  A  large,  randomized,  double-blind  placebo-controlled  trial  of  succimer  in  children  with  blood  lead  concentrations  between  25  and  44  mcg/dL  found  no  evidence  of  benefit  in  clinical  outcome  or  long-term  blood  lead  reduction.Succimer  is  protective  against  the  acute  lethal  and  nephrotoxic  effects  of  mercuric  salts  in  animal  models  and  increases  urinary  mercury  excretion  in  animals  and  humans.  It,  therefore,  may  have  clinical  utility  in  the  treatment  of  human  poisoning  by  inorganic  mercury.  In  a  recent  animal  model  of  methylmercury  exposure  during  pregnancy,  succimer  was  effective  in  reducing  the  maternal  and  fetal  mercury  burden;  however,  unithiol  appeared  to  be  somewhat  more  potent  in  that  setting.Succimer  is  protective  against  the  acute  lethal  effects  of  arsenic  in  animal  models  and  may  have  potential  utility  in  acute  human  arsenic  poisoning.Contraindications.  History  of  allergy  to  the  drug.  Because  succimer  and  its  transformation  products  undergo  renal  elimination,  safety  and  efficacy  in  patients  with  severe  renal  insufficiency  are  uncertain.  There  is  no  available  evidence  that  succimer  increases  the  hemodialysis  clearance  of  toxic  metals  in  patients  with  anuria.Adverse  effectsGastrointestinal  disturbances  including  anorexia,  nausea,  vomiting,  and  diarrhea  are  the  most  common  side  effects  and  occur  in  fewer  than  10%  of  patients.  There  may  be  a  mercaptan-like  odor  to  the  urine;  this  has  no  clinical  significance.Mild,  reversible  increases  in  liver  transaminases  ...