Digoxin Toxicity

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     1  Digoxin Toxicity AM Report Josh Spencer 5-16-07
     2  Overview Cardiac glycoside toxicity potentially fatal with mortality ranging from 3-50% Caused by numerous substances usually by digitalis (one form is Digoxin) EKG findings Now with good treatment
     3  Numbers Trial with 150 patients with dig toxicity overdose occurred with: 50% taking longterm therapy 10% large accidental overdose 40% suicidal attempt
     4  Conditions leading to Dig Toxicity Renal insufficiency/ESRD ESRD prolongs half-life and reduces volume of distribution Advanced age Cardiac diseases Active ischemia, myocarditis, cardiomyopathy, amylodosis, cor pulmonale Metabolic factors Hypokalemia, hypomag, hypoxemia, hypernatremia, hypercalcemia, acid-base
     5  Drugs Affecting Dig Levels Quinindine, cyclosporine, verapamil, diltiazem, tetracycline, erythromycin, SSRI’s Most drugs raise levels by reducing excretion Rifampin Induces enzymes--look out for toxicity when rifampin discontinued
     6  Pharmacology Inhibits vagal tone Cardiac muscle depolarization Na and Ca enter myocardial cells Repolarization Na and Ca out of cell Na by Na-K-ATPase, Ca by Na-Ca transporter (driven by Na transmembrane gradient) Dig inhibits Na-K-ATPase Increasing intracellular Na reducing gradient Na-Ca driving force reduced increasing intracellular Ca--increasing cardiac contractility; positive ionotropic effect
     7  Dig Affects on Cardiac Muscle Due to increased intracellular Ca and increased vagal tone the below can produce conditions conducive to the development of reentrant arrhythmias. Enhance and depress automaticity Delayed afterpotentials Increase or decrease excitability Slow conduction Alter refractoriness
     8  Kinetics Digoxin bioavailability is 80% Half-life 1.6 days Major storage area in body skeletal muscle Not removed by HD 1/3 body stores/day excreted 30% Unchanged in urine 3% as metabolites in stool
     9  Signs/Syptoms of Dig Overdose History suggesting change in Dig dosage History of any other new drugs Fatigue, blurred vision, disturbed color perception, N/V, anorexia, diarrhea, abdominal pain, HA, dizziness, confusion, delirium, hallucinations Bradycardia Occasional tachycardia Hypotension in severe cases
     10  K Hyperkalemia Hyperkalemia in acute settings shows degree of Na-K-ATPase poisoning If K <5 then mortality 0% If K >5 mortality 50% K >5.5 mortality 100% Above numbers before advent of treatment Hypokalemia Potentiates toxicity--correct immediately
     11  ECG Normal Dig on ECG
     12  ECG-normal T wave changes QT interval shortening “Scooped” appearance of ST segment Increase U wave amplitude
     13  ECG changes with Dig toxicity Ventricular ectopy-PVC’s Atrial tachyarrhythmias and AV nodal depression cause high degree AV block PAT with Block-some say nearly pathognomonic Ventricular arrhythmias Accelerated junctional rhythm-specific Bidirectional ventricular tachycardia-specific Almost any rhythm except SVT with 1:1 conduction can be seen
     14  Atrial Tachycardia with AV block
     15  First Degree AV block
     16  Mobitz I
     17  Afib with accelerated Junctional Rhythms
     18  Bidirectional Ventricular Tachycardia
     19  Ventricular Bigeminy
     20  Treatment Support treatment if needed-intubation, etc Symptomatic bradycardia-atropine Do not use transvenous pacing-can lead to arrhythmias Avoid Beta agonists (isoproterenol) Gut decontamination with activated charcoal (w/in 6-8 hours of acute ingestion) Manage K as usual except do not use calcium salts Replace Mg
     21  TreatmentDigibind Digoxin-specific Fab fragments Made in sheep Bind rapidly to intravascular dig Dig stored in other tissues then goes into intravascular space and digibind binds that also Digibind/digoxin complex small and is rapidly removed by normal kidneys ESRD on HD responds clinically the same to digibind except elimination of complex slow Theoretically can get rebound dig toxicity
     22  When to Use Digibind Hemodynamic instability Life-threatening arrhythmias Severe Bradycardia-even if atropine works Plasma K above 5 Plasma Dig above 10 Presence of dig toxicity rhythm combined with dig toxic level
     23  Response Time Mean response time 19 minutes Range of complete response 30min to 4 hours
     24  Side effects of Digibind Exacerbation of CHF Increase in vent response to afib/flutter Hypokalemia Allergic reactions Plasma Dig level measurement unreliable after given digibind
     25  Dosing Digibind Give over 30min Vials of digibind= [dig level(ng/ml) X mass (kg)/100. Round up results Ex. 4.2 rounds to 5 If digitalis toxic due to herbs give 5-10 vials
     26  References http://www.sciencedirect.com.libproxy.lib.unc.edu/science?_ob=ArticleURL&_udi=B6T8B-42C07N1-8&_user=130907&_coverDate=02%2F28%2F2001&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000004198&_version=1&_urlVersion=0&_userid=130907&md5=461c196c5db7aa1916fb4a1dec1035dd Ismail, Nuhad, MD. Digitalis (cardiac glycoside) intoxication. UpToDate. 2007. Arnsdorf, Morton, MD. Electrophysiology of arrythmias due to digitalis toxicity. UpToDate. 2007.