1. Digoxin Toxicity DR TIMOURI H

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 changesT wave changes »QT interval shorteningQT interval shortening »“Scooped” appearance of ST segment“Scooped” appearance of ST segment »Increase U wave amplitudeIncrease 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. Treatment Digibind »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?_o b=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=461c196c 5db7aa1916fb4a1dec1035dd »Ismail, Nuhad, MD. Digitalis (cardiac glycoside) intoxication. UpToDate. 2007. »Arnsdorf, Morton, MD. Electrophysiology of arrythmias due to digitalis toxicity. UpToDate. 2007.