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POISONING BY
CARDIOVASCULAR DRUGS
                       Ayman Zaaqoq
                           Lecturer
 Department of Forensic Medicine and Clinical Toxicology, ASU
                         2012-2013
CV TOXICITY

                          CV toxicity



           Bradycardia                  Tachycardia


                           Calcium
Digoxin   Beta-blockers    channel      Theophylline
                           blockers
CV TOXICITY
                INVESTIGATIONS


                                 Investigation


                           Laboratory        ECG


S. drug level    Glucose     S.K+            KFTs   ABG
TOXICITY TREATMENT
     GENERAL GUIDELINES
                                        Treatment



Stabilization   Decontamination        Elimination   Antidote           Supportive



                                  MDAC: dig.,                              Bradycardia,
                  GL                theo              Very high level         AVB


                                                                            Ventricular
                  AC              Dialysis: theo       Serious C/P         dysrhythmias



                                                        Huge dose         Hyperkalemia
TREATMENT OF SERIOUS
     DYSRHYTHMIAS
              TdP                V-tach

 MgSO4 IV            Cardioversion

 Overdrive pacing    NaHCO3 IV

 Cardioversion       Lignocaine

 Phenytoin           Phenytoin

                      Esmolol
DIGOXIN TOXICITY
DIGOXIN TOXICITY
             SOURCES

 Pharmaceutical preparations:
Lanoxin®, Cardixin®

 Plants: oleander

 Animals: cane toad
DIGOXIN TOXICITY
              FORMS
            Acute              Chronic

 Accidental         Therapeutic error

 Intentional        Decreased elimination
DIGOXIN TOXICITY
              MECHANISM

                               Digoxin


                                                Changes
           Θ Na+/K+-          Vagotonic        refractory
            ATPase                               period


↑ intracellular   ↑ extracellular                      ↓ in atria and
     Na+                K+           ↑ in AV node
                                                         ventricles
DIGOXIN TOXICITY
           ACTIONS


                     Digoxin


                  ↓             ↑
↑ inotropy                                ↑ potassium
             chronotropy   automaticity
DIGOXIN TOXICITY
     CLINICAL PICTURE


              C/P

                Potassium
CV       GI                 Visual
                imbalance
DIGOXIN TOXICITY
        INVESTIGATIONS


                     Investigation


               Laboratory        ECG


S.K+     SDC     KFTs            ABG   Glucose
DIGOXIN TOXICITY
         INVESTIGATIONS

 ECG changes
    • Due to digoxin intake
    • Due to digoxin toxicity
    • Due to potassium
      disturbances
    • Due to pre-existing cardiac
      condition
DIGOXIN TOXICITY
                   TREATMENT

                                  Treatment



Stabilization                                   Antidote         Supportive
                Decontamination   Elimination
 (antidote)


                                                                           Ventricular
                 GL (?)                 MDAC         Bradycardia, AVB     dysrhythmias



                  AC                                   Hyperkalemia
DIGOXIN TOXICITY
ANTIDOTE: DIGIBIND

                 Indications


    Laboratory       Clinical   History


 S.K+          SDC


        High     Unavailable
BETA-BLOCKER
  TOXICITY
BETA-BLOCKER TOXICITY
       MECHANISM


                BB

β-receptor   Na channel     Lipid
 blockade     blockade    solubility
BETA-BLOCKER TOXICITY
        ACTIONS


                       BB


                  ↓
↓ inotropy   chronotropy
                            Wide QRS   Θ CNS
BETA-BLOCKER TOXICITY
   CLINICAL PICTURE


         C/P

CVs     CNS    Metabolic
BETA-BLOCKER TOXICITY
   INVESTIGATIONS

                 Investigation


           Laboratory        ECG


 Glucose     S.K+           KFTs
DIGOXIN TOXICITY
             TREATMENT
                            Treatment



                                         Antidote
Stabilization   Decontamination                                 Supportive
                                        (Glucagon)


                                                 Bradycardia,
                  GL                                                         Wide QRS
                                                 hypotension



                  AC                                 Seizures           Hypoglycemia
CALCIUM CHANNEL
   BLOCKERS
CALCIUM CHANNEL
             BLOCKERS
 They block slow Ca channels of vascular smooth muscles and
cardiac muscles.


 Acute toxicity is similar to B-blockers


 Treatment is as in B-blockers. In addition, CaCl2 10% 10ml IV
over 10 min for hypotension and myocardial depression.
THEOPHYLLINE
  TOXICITY
THEOPHYLLINE TOXICITY
        MODE

                  Mode of
                  poisoning


         Intentional    Dosing errors


                                 Change in the   Reduced
Parent error    Miscalculation
                                  frequency      clearance
THEOPHYLLINE TOXICITY
     MECHANISM


          Theophylline



↓cGMP &     Adenosine
  cAMP    receptor block   ↑catecholamines
THEOPHYLLINE TOXICITY
        C/P
              Nausea and
    GIT        vomiting
                            Hematemesis      Hypovolemic
                                                shock



                             Irritability,     Seizures,
    CNS         Anxiety
                              tremors           coma



                 Sinus      Ventricular      Cardiogenic
    CVS       tachycardia   tachycardia        shock



                             Metabolic
  Metabolic   Hypokalemia
                             acidosis
THEOPHYLLINE TOXICITY
     INVESTIGATIONS


                               Investigation


                         Laboratory        ECG


    S.
               Glucose     S.K+            KFTs   ABG
Theophylline
THEOPHYLLINE TOXICITY
             TREATMENT

                                         Treatment




Stabilization   Decontamination                Elimination      Antidote      Supportive




                   GL             MDAC         Hemodialysis   Hemoperfusion




                Emesis (?)
THEOPHYLLINE TOXICITY
           TREATMENT


                                           Supportive
                                            treatment



            Tachycardia      Hypokalemia   Hypotension   Seizures   Vomiting



Supraventricluar     Ventricular
Poisoning by cardiovascular drugs

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Poisoning by cardiovascular drugs

  • 1. POISONING BY CARDIOVASCULAR DRUGS Ayman Zaaqoq Lecturer Department of Forensic Medicine and Clinical Toxicology, ASU 2012-2013
  • 2. CV TOXICITY CV toxicity Bradycardia Tachycardia Calcium Digoxin Beta-blockers channel Theophylline blockers
  • 3. CV TOXICITY INVESTIGATIONS Investigation Laboratory ECG S. drug level Glucose S.K+ KFTs ABG
  • 4. TOXICITY TREATMENT GENERAL GUIDELINES Treatment Stabilization Decontamination Elimination Antidote Supportive MDAC: dig., Bradycardia, GL theo Very high level AVB Ventricular AC Dialysis: theo Serious C/P dysrhythmias Huge dose Hyperkalemia
  • 5. TREATMENT OF SERIOUS DYSRHYTHMIAS TdP V-tach  MgSO4 IV  Cardioversion  Overdrive pacing  NaHCO3 IV  Cardioversion  Lignocaine  Phenytoin  Phenytoin  Esmolol
  • 7. DIGOXIN TOXICITY SOURCES  Pharmaceutical preparations: Lanoxin®, Cardixin®  Plants: oleander  Animals: cane toad
  • 8. DIGOXIN TOXICITY FORMS Acute Chronic  Accidental  Therapeutic error  Intentional  Decreased elimination
  • 9. DIGOXIN TOXICITY MECHANISM Digoxin Changes Θ Na+/K+- Vagotonic refractory ATPase period ↑ intracellular ↑ extracellular ↓ in atria and Na+ K+ ↑ in AV node ventricles
  • 10. DIGOXIN TOXICITY ACTIONS Digoxin ↓ ↑ ↑ inotropy ↑ potassium chronotropy automaticity
  • 11. DIGOXIN TOXICITY CLINICAL PICTURE C/P Potassium CV GI Visual imbalance
  • 12. DIGOXIN TOXICITY INVESTIGATIONS Investigation Laboratory ECG S.K+ SDC KFTs ABG Glucose
  • 13. DIGOXIN TOXICITY INVESTIGATIONS  ECG changes • Due to digoxin intake • Due to digoxin toxicity • Due to potassium disturbances • Due to pre-existing cardiac condition
  • 14. DIGOXIN TOXICITY TREATMENT Treatment Stabilization Antidote Supportive Decontamination Elimination (antidote) Ventricular GL (?) MDAC Bradycardia, AVB dysrhythmias AC Hyperkalemia
  • 15. DIGOXIN TOXICITY ANTIDOTE: DIGIBIND Indications Laboratory Clinical History S.K+ SDC High Unavailable
  • 17. BETA-BLOCKER TOXICITY MECHANISM BB β-receptor Na channel Lipid blockade blockade solubility
  • 18. BETA-BLOCKER TOXICITY ACTIONS BB ↓ ↓ inotropy chronotropy Wide QRS Θ CNS
  • 19. BETA-BLOCKER TOXICITY CLINICAL PICTURE C/P CVs CNS Metabolic
  • 20. BETA-BLOCKER TOXICITY INVESTIGATIONS Investigation Laboratory ECG Glucose S.K+ KFTs
  • 21. DIGOXIN TOXICITY TREATMENT Treatment Antidote Stabilization Decontamination Supportive (Glucagon) Bradycardia, GL Wide QRS hypotension AC Seizures Hypoglycemia
  • 22. CALCIUM CHANNEL BLOCKERS
  • 23. CALCIUM CHANNEL BLOCKERS  They block slow Ca channels of vascular smooth muscles and cardiac muscles.  Acute toxicity is similar to B-blockers  Treatment is as in B-blockers. In addition, CaCl2 10% 10ml IV over 10 min for hypotension and myocardial depression.
  • 25. THEOPHYLLINE TOXICITY MODE Mode of poisoning Intentional Dosing errors Change in the Reduced Parent error Miscalculation frequency clearance
  • 26. THEOPHYLLINE TOXICITY MECHANISM Theophylline ↓cGMP & Adenosine cAMP receptor block ↑catecholamines
  • 27. THEOPHYLLINE TOXICITY C/P Nausea and GIT vomiting Hematemesis Hypovolemic shock Irritability, Seizures, CNS Anxiety tremors coma Sinus Ventricular Cardiogenic CVS tachycardia tachycardia shock Metabolic Metabolic Hypokalemia acidosis
  • 28. THEOPHYLLINE TOXICITY INVESTIGATIONS Investigation Laboratory ECG S. Glucose S.K+ KFTs ABG Theophylline
  • 29. THEOPHYLLINE TOXICITY TREATMENT Treatment Stabilization Decontamination Elimination Antidote Supportive GL MDAC Hemodialysis Hemoperfusion Emesis (?)
  • 30. THEOPHYLLINE TOXICITY TREATMENT Supportive treatment Tachycardia Hypokalemia Hypotension Seizures Vomiting Supraventricluar Ventricular