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  • Cardioactive Steroids (CAS) & Digoxin

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    Elora Apantaku
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    Cardioactive steroids like digoxin are derived from plants and have been used medically since ancient times. Digoxin increases the force of heart contraction through its effects on intracellular calcium levels. Therapeutic doses cause positive inotropic effects while toxic doses can cause cardiac arrhythmias and other toxicities through hyperkalemia. Digoxin has a long half-life, is primarily renally eliminated, and is subject to many drug interactions. Clinical effects of digoxin toxicity range from nausea and vomiting acutely to cardiac arrhythmias chronically. Management involves supportive care, activated charcoal, digoxin-specific antibody fragments, atropine, and treatment of arrhythmias.

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    Toxicology of cardioactive steroids including digoxin.

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    Cardioactive steroids like digoxin are derived from plants and have been used medically since ancient times. Digoxin increases the force of heart contraction through its effects on intracellular calcium levels. Therapeutic doses cause positive inotropic effects while toxic doses can cause cardiac arrhythmias and other toxicities through hyperkalemia. Digoxin has a long half-life, is primarily renally eliminated, and is subject to many drug interactions. Clinical effects of digoxin toxicity range from nausea and vomiting acutely to cardiac arrhythmias chronically. Management involves supportive care, activated charcoal, digoxin-specific antibody fragments, atropine, and treatment of arrhythmias.

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    2 views8 pages

    Cardioactive Steroids (CAS) & Digoxin

    Uploaded by

    Elora Apantaku
    Cardioactive steroids like digoxin are derived from plants and have been used medically since ancient times. Digoxin increases the force of heart contraction through its effects on intracellular calcium levels. Therapeutic doses cause positive inotropic effects while toxic doses can cause cardiac arrhythmias and other toxicities through hyperkalemia. Digoxin has a long half-life, is primarily renally eliminated, and is subject to many drug interactions. Clinical effects of digoxin toxicity range from nausea and vomiting acutely to cardiac arrhythmias chronically. Management involves supportive care, activated charcoal, digoxin-specific antibody fragments, atropine, and treatment of arrhythmias.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
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    of 8

    Cardioactive Steroids (CAS) &

    Digoxin

    by elora apantaku
    Epidemiology and History
    ● Cardioactive plants have been used since ancient times.
    ● Foxglove (Digitalis spp.) was first studied in-depth in 1785 for the
    treatment of edema and as a diuretic.
    ● CAS-containing plants: oleanders, foxglove, lily of the valley, dogbane
    ● CAS- containing drugs: digoxin, digitoxin, ouabain, lanatoside C,
    Deslanoside, gitalin
    ● Between 2011-2015,
    ○ 7,000 CAS-containing plant exposures with 5 deaths;
    ○ 12,000 CAS-containing xenobiotics with > 120 deaths.

    Digoxigenin
    Mechanism of Action & Toxicity
    Therapeutic dosing:
    ● Increase force of heart contraction (positive inotropic effect) by
    increasing Ca2+ during systole.
    ● Inhibits the sodium-potassium-ATPase pump, increasing intracellular
    Na+, which increases Ca2+.

    Toxic dosing:
    ● Hyperkalemia (hypokalemia in chronic dosing)
    ● Increased vagal tonicity which slows heart rate.
    ● Increased atrial and ventricular dysrhythmias because of increased
    intracellular calcium.
    Pharmacokinetics
    Absorption Bioavailability 60-80% (digoxin), maximal effect 4 - 6 hours

    Distribution Vd= 5-10 L/kg (digoxin)

    Metabolism 7% undergoes enterohepatic circulation

    Elimination T1/2 = 30-50 hours, renal (60-80%)

    Drug-Drug Interactions Amiodarone, verapamil, diltiazem, quinidine, macrolide antibiotics


    (effects GI flora absorption)
    Clinical Presentation

    Acute: nausea, vomiting, Chronic: nausea, anorexia,


    hyperkalemia, and cardiac anhedonia, abdominal pain, visual
    disturbances (flashing lights, halos,
    arrhythmias↟. yellow perceptual impairment),
    ↟ Includes sinus bradycardia, sinoatrial weakness, fatigue, sinus
    arrest, second- or third-degree AV bradycardia, atrial fibrillation with
    block, paroxysmal atrial tachycardia
    slowed ventricular response rate or
    junctional escape rhythm, and
    with AV block, accelerated junctional
    ventricular arrhythmias.
    tachycardia, ventricular bigeminy,
    ventricular tachycardia, bidirectional Hypokalemia and hypomagnesemia may
    ventricular tachycardia, ventricular be present.
    fibrillation, and asystole. Altered mental status common in elderly
    (confusion, depression, and
    hallucinations).
    Management

    1. ABCs
    2. Stop offending agent
    3. N/A
    4. Multidose Activated Charcoal: 1g/kg q2-4 hrs x 4 doses
    5. Labs:
    a. Serum digoxin (normal 0.5 -1ng/mL) at 6 hours
    b. BMP, magnesium, BUN, creatinine, EKG
    Supportive care involves repleting potassium, magnesium, and calcium
    Treatment
    Digoxin-Specific Antibody Fragments
    Indications:
    ● Any life-threatening dysrhythmias
    ● Potassium concentrations > 5 mEq/L
    ● [Digoxin] > 15 ng/mL at any time or >10 ng/mL 6 hours post-
    ingestion, regardless of symptoms
    ● Acute ingestion of 10 mg in adult
    ● Acute ingestion of 4 mg in child
    Dosing:
    ● Empiric Acute: 10 - 20 vials
    ● Empiric Chronic: 3 - 6 (adults), 1-2 (children)
    Additional Treatment

    Atropine
    For bradycardia or heart block
    Dosing: 0.5 - 2 mg IV

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