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    Toxicology Lecture 5 - Digoxin

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    Digoxin is a cardiac glycoside commonly used to treat heart failure and arrhythmias, but can cause toxicity by inhibiting the sodium-potassium pump leading to cardiac arrhythmias and other signs and symptoms. Risk factors for digoxin toxicity include renal impairment, electrolyte abnormalities, aging, and drug interactions that decrease its clearance or conduction. Management involves preventing further absorption, enhancing elimination such as with hemodialysis, treating symptoms, and using Digibind which binds digoxin to form a complex that is excreted in urine.

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    Toxicology Lecture 5 - Digoxin

    Uploaded by

    yousername
    49 views29 pages
    Digoxin is a cardiac glycoside commonly used to treat heart failure and arrhythmias, but can cause toxicity by inhibiting the sodium-potassium pump leading to cardiac arrhythmias and other signs and symptoms. Risk factors for digoxin toxicity include renal impairment, electrolyte abnormalities, aging, and drug interactions that decrease its clearance or conduction. Management involves preventing further absorption, enhancing elimination such as with hemodialysis, treating symptoms, and using Digibind which binds digoxin to form a complex that is excreted in urine.

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    Toxicology Lecture 5_Digoxin

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    Digoxin is a cardiac glycoside commonly used to treat heart failure and arrhythmias, but can cause toxicity by inhibiting the sodium-potassium pump leading to cardiac arrhythmias and other signs and symptoms. Risk factors for digoxin toxicity include renal impairment, electrolyte abnormalities, aging, and drug interactions that decrease its clearance or conduction. Management involves preventing further absorption, enhancing elimination such as with hemodialysis, treating symptoms, and using Digibind which binds digoxin to form a complex that is excreted in urine.

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    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    49 views29 pages

    Toxicology Lecture 5 - Digoxin

    Uploaded by

    yousername
    Digoxin is a cardiac glycoside commonly used to treat heart failure and arrhythmias, but can cause toxicity by inhibiting the sodium-potassium pump leading to cardiac arrhythmias and other signs and symptoms. Risk factors for digoxin toxicity include renal impairment, electrolyte abnormalities, aging, and drug interactions that decrease its clearance or conduction. Management involves preventing further absorption, enhancing elimination such as with hemodialysis, treating symptoms, and using Digibind which binds digoxin to form a complex that is excreted in urine.

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    MEDICAL

    TOXICOLOGY
    DIGOXIN
    DR.Eman Mantawy
    Digitalis
     Digitalis is one of cardiac glycosides,
    present maily in Digitalis Purpurea
    (foxglove)
     Cardiac glycosides comprise a group
    of steroidal compounds used in the
    treatment of congestive heart failure
    (CHF).

     The two most commonly used


    digitalis glycosides are digoxin and
    digitoxin.
    Digoxin

    Formulations
    Lanoxin
    (Tablets, Injections ,Elixir)

    Therapeutic uses

    - Congestive heart failure


    - Atrial fibrillation
    - Supraventricular tachycardia
    Toxicodynamics
    1-They increase the cardiac output by exerting a
    positive ionotropic action HOW ?????????????
    A) Inhibiting Na+/K+ ATPase (sodium pump) which pumps 3
    Na+ outside the cell in exchange with 2 K+ inside the cell
    which is responsible for maintenance of resting membrane
    potential (RMP) in most excitable cells

    Relative reduction of Ca+ expulsion from the cell by


    Na+/Ca+ exchanger caused by the increase of
    intracellular Na+.
    Toxicodynamics
    Toxicodynamics
    More intracellular Ca Intracellular Na

    Release of Ca
    from
    sarcoplasmic
    reticulum
    Toxicodynamics
    2-They exert negative chronotropic effect through
    vagal and extravagal stimulation.
    -ve dromotropic
    effect +ve bathmotropic
    effect

    3-They decrease AV conduction through direct


    action on the myocardium and vagal stimulation.

    4-They increase heart automaticity in overdose as when


    conduction and the normal pacemaker are both
    depressed, ectopic pacemakers may take over,
    producing atrial and ventricular tachycardia .
    Signs & symptoms
    A) Cardiac
    Dysrrhythmia
    - Decrease AV conduction leading to bradycardia and heart
    block : First
    Second Conduct all pulses but slowly
    one or more (but not all) of the
    atrial impulses fail to conduct
    to the ventricles due to
    impaired conduction.
    Third Complete heart block
    -Increase automaticity leading to several types of
    tachyarrhythmias.
    Signs & symptoms
    Signs & symptoms

    B) Non cardiac
    GIT manifestations

    Nausea, vomiting, abdominal pain, anorexia

    Nausea and vomiting


    Digitalis preparation where the preparation
    and leaves increases vagal
    stimulation and activate
    (CTZ)
    Leaves Local irritation
    Signs & symptoms

    B) Non cardiac
    CNS manifestation

    Psychic disturbance Hallucination, confusion and


    (personality changes) disorientation, amnesia

    Nightmares Convulsions
    Signs & symptoms

    B) Non cardiac
    Visual disturbance
    Colored vision (yellow and green patches)

    Scotomata (Isolated areas of Diplopia


    varing size and shape in which the
    vision is absent)
    Signs & symptoms

    B) Non cardiac

    Endocrine disturbance

    Due to steroidal nature

    Gynaecomastia Menstrual disturbance


    Signs & symptoms

    B) Non cardiac
    Electrolyte disturbance
    Hyperkalemia in acute toxicity

    Hypokalemia in chronic toxicity


    Signs & symptoms

    B) Non cardiac
    Electrolyte disturbance
    Both hypokalmeia and hyperkalemia increase digitalis
    toxicity WHY??

    Hypokaleima allows Hyperkalemia decreases


    digitalis to act on the Na/K AV conduction so
    ATP ase pump without enhances digitalis toxicity
    competition
    Toxicokinetics

    -There are two types of digitalis glycosides: digoxin and


    digitoxin.

    -They differ in their kinetics where as the number of OH


    groups on steroidal nucleus decreases, the polarity
    decreases, the lipophillicity increases, and the absorption
    increases.

    -Digitoxin is metabolized by the liver to both active and


    inactive products because of enterohepatic circulation
    Toxicokinetics
    Item Digoxin Digitoxin

    GIT absorption More OH gp on


    steroidal nucleus
    less lipid solubility
    less absorption
    60-85% 90-100%
    Onset of action 15-30 mins 0.5-2 hrs

    Plasma albumin 25% 97%


    binding Vd Vd
    (tissue bound)
    Toxicokinetics
    Item Digoxin Digitoxin

    Toxic levels 2.4 34


    ng/ml
    Half life 36 hrs 5-7 days
    (enterohepatic
    recirculation)
    Excretory Renal Hepatic
    pathway
    Risk factors
    Renal diseases
    Digoxin is mainly eliminated via kidney thus renal
    injury will decrease its excetion

    Aging
    Elderly are more likely to have decreased renal
    function

    Fluid status
    Fluid loss or poor fluid intake can lead to electrolyte
    imbalance
    Risk factors
    Electrolyte imbalance

    Hypokalemia Hypercalcemia Hypomagnesemia


    Increased Sensitize heart to
    digoxin binding
    Ca overload digoxin effects as
    to the Na/K enhancing can cause
    ATPase pump digoxin hypokalemia via
    due to impairing
    inotropic Na/KATPase,
    decreased
    completion effect decreasing
    with potassium cellular uptake of
    K
    Risk factors
    Drug interactions
    A) Drugs decreasing AV conduction
    Beta blockers, Verapamil, Deltiazem,
    Amiodarone, Qunidine

    B) Drugs decreasing digoxin clearance


    Verapamil, Deltiazem, Amiodarone, Qunidine
    Risk factors
    Drug interactions
    C) Drugs causing hypokalemia
    Loop (furosemide) & thiazide (hypochlorothiazide)
    diuretics, licorice (Na water retention)

    D) Drugs decreasing decreased gut flora


    Broad spectrum Abs; Erythromycin, Ciprofloxacin,
    Tetracyclines
    N.B: gut flora that degrades digoxin
    Management
    1- ABCD
    2- Prevent any further absorption
    Gastric lavage (Atropine??)

    Activated charcoal (Repeated dosing)

    Cholestyramine ( binds acidic drugs)


     Induced emesis with ipecac syrup - Not
    recommended, because of the increased vagal
    effect
    Management
    3-Enhance elimination

    Hemodialysis and hemoperfusion

    Digitalis is bound to tissues


    Management

    3-Symptomatic and supportive treatment

    *Tachycardia lidocaine or phenytoin


    *Bradycardia Atropine
    Insulin + glucose to shift K+
    *Hyperkalemia
    intracellularly, Avoid Ca gluconate
    ?????
    *Hypokalemia K+ supplement

    * EDTA & To shift extra intracellular calcium


    extracellularly give EDTA
    Management
    4) Specific antidote Digibind
    1
    2
    Inject digoxin
    Take antiserum
    in sheep

    Autogenicity
    Abs formed & elimination
    against digoxin
    4
    Remove Fc
    & take FAB
    Inject FAB FAB portion
    portion in
    human 3
    Fc
    Management
    Digibind
    Fab binds to digoxin extracellularly

    Forming a complex excreted in the urine

    Digoxin moves from inside to the outside of the cell

    N.B: (Less effective in case of chronic toxicity).


    Management
    Digibind
    Contraindications
    - Patients with known hypersensitivity to ovine (sheep)
    products
    - Patients previously treated with these antibodies as Fab
    fragments are themselves immunogenic, patients treated
    more than once may experience an acute hypersensitivity
    reaction
    Side effects
    Re-intoxication, due to complex degradation in patients
    with impaired renal clearance due to impaired elimination
    of digoxin-Fab complex

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