DIGOXIN

 

Overview:                                                         

  1. Inotrop  (+)ve,  Cronotrop  (-)ve,  Slows  conduction  in  SA  &  AV  node. These  occur  by :
      1. inhibiting  Na/K  pump  ATPase  that  results  in  higher   intracellular  Na  and  Ca,  which in   turn  enhances cardiac  muscles  to  contract
         
      2. vagal  tone  enhancement  with  consequent  slowing   of    SA  &  AV  node
         
      3. increase  of  extracellular  K.
         
  2. IV  peak  effect  is 1- 4hrs, PO peak  effect  - 2- 6hrs.
     
  3. Given  the  large  Vd  that affects the  peak  level  and  because  DIG concentrates  in  tissues,serum levels do  not  always  accurately  reflect  the  amount  of  drug   in  the body.
     
  4. Factors that predispose to toxicity and OD are age , hypokalemia , hypomagnesemia ,   hypercalcemia, CRF,  liver  dysfunction , hypothyroidism , Quinidine , Ca  blockers, NSAIDs.

S & S:

  1. Non Cardiac:
     
    1. CNS -fatigue, weakness,  confusion,  diplopia,  visual  aberration.
       
    2. GI- anorexia,  N/V, diarrhea
      Note!   together  they may be reminiscent  of  flu-like  symptoms
       
  2. Cardiac:       
    1.   PVC - most  common  arrhythmia
       
    2.   PSVT with  AV  block - most  specific arrhythmia
       
    3.   Bradyarrhythmia
       
    4.   Bi-directional  V  tach -specific arrhythmia, but  rare
       
    5. Junctional  arrhythmia.
       
    6. Note  that   ventricular  arrhythmias  are  more  common  with  chronic  toxicity
       
  3. Symptoms also vary if toxicity is a result of chronic high dose ingestion or acute high dose ingestion

Chronic

Acute

Elderly

Young

GI Effects

GI Effects

Normal or < K

HyperK

Ventricular Arrhythmia

PVC's, PSVT with AV block

Quasi normal dig level

Elevated serum dig level
 

 

 

 

 

Treatment:

  1. Lavage,charcoal (repeat doses can be given since enterohepatic circulation exists), cathartics, antiemetic (important: charcoal may not be kept down since Dig causes N/V)
     
  2. If pt is asymptomatic-observe, cardiac monitor, AC 1gm/kg, frequent evaluations.
         
  3. Bradyarrhythmias with symptoms ( MS, Hemodynamically unstable), treat as follows:
     
    1. Atropine 0.5-2.0 mg IV.
       
    2. Pacemaker (can be dangerous)
       
    3. Fab. 10 vials are given if ingested amount is unknown
       
  4. Ventricular  arrhythmias
     
    1. Fab. 10 vials are given if ingested amount is unknown
       
    2. Phenytoin 15 - 20 mg/kg @ 25mg/min or  Lidocaine 1-1.5 mg/kg IV- they  depress   ventricular arrhythmia  without  effect  on  AV  node. No  effect  on  supraventricular   rhythm
       
    3. MgSO4 2-4 mg IV
       
    4. Propranolol  can  suppress   both  supra  and  ventricular  arrythmias,  yet it may adversely  affect AV  node
       
  5. CPR
     
    1. Standard  ACLS - yet controversy exists about cardioversion and most recommend starting at lower  voltage.
       
    2. Fab
       
  6. HyperK
     
    1. High  mortality  when  level  is  >5.5
       
    2. Do  not  use  Ca  Chloride  or  Gluconate. Ca is already elevated intracellularly and further elevation will cause arrythmias.
       
    3. D50, Insulin, NaHco3, Kayexalate. These are only temporizing measures.
       
    4. Fab is the best choice in treating hyperkalemia related to dig toxicity.
       
    5. Dialysis to remove K. Not efficient to remove Dig.

 

INDICATIONS   FOR   FAB (Digibind):                                

  1. Ventricular  arrhythmia
     
  2. Bradyarrhythmia
     
  3. Hyperkalemia  >5.5
     
  4. Renal failure  

Formula for proper dosage:

dig level  x  body wgt   = number of vials

             100

 if level is unknown, 10 vials are given.

 FAB is administered IV over 15-20 min.

 It takes 30-60 min for FAB to take effect.

Administration of FAB can result  in  some  adverse  effects:

  1. cardiogenic  shock  in  people  dependent   on  dig  for  inotropic  support.
     
  2. allergic  reaction  - in  people  with  strong  allergy  hx,  skin  testing   is  recommended.
     
  3. increase  in  total  level  of   serum   dig - this  occurs  because  dig  exits  from  tissues,  yet it has no  clinical  importance
     
  4. it  takes 16-20 hr. for dig/fab  complex  to  be  eliminated   by  kidney,  and only  then  serum dig level can be accurately measured.
     
  5. administration of Fab  should result in  normalization of EKG, if  the EKG changes were really due to dig toxicity

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