1. 1. By: Alaa Atteya AboDonia
2. 2. Presonal history Female patient Aged 70 years From , Alexandria Housewife Haschildren Admitted on .. The Complaint: Persistent vomiting & easy fatigability and dizziness since 1 1/2month
3. 3. History of the present complain Condition started 1 and month ago by acute onset of attacks of persistent vomiting , associated with nausea and epigastric pain, not related to food intake, no fever, no blood in stool, the pateint sought medical advice and received medications for gastroenteritis but no improvement Condtion progressed and easy fatigability and dizziness associated with blurred vision occurs and sometimes presyncope but no syncopal attack Sought medical advice again and IV fluids was given with no improvement
4. 4. History of the present complain Presented to our internal medicine clinic and was admitted to our hospital for workup
5. 5. Family history: Irrelevant Past History HTN since 1 y Mild mitral regurgitation( degenerative) No DM Recurrent UTI Surgical history: Lt Nephrectomy sine 7 years on top of pyelonephritis Cataract surgery since 4 years Drug & transfusion history: Coversyl 5 mg , Concor 5 mg, Lanoxin 0.25 , PPI, Motillium
6. 6. Examination on admission General: concious , alert Vital signs: B.P = 110 / 70 , Rt=Lt Pulse: 40 bpm, regular, equal bilateral, average force and volume Temp.=37 c Head and neck: No thyroid enlargement. No jaundice , No central cyanosis. Extremities: No odema No peripheral cyanosis No clubbing
7. 7. Cardiac examination Neck veins: Normal pressure& pulsations Hepatojugular reflux -ve Emptying with inspiration Inspection of the heart: The apical heartbeat visible in the mid- clavicular line at the 5th intercostal space Palpation of the heart: Apex located in the Lt mid-clavicular line at the 5th intercostal space, localized . Percussion no dullness outside apex and Rt sternal border, reasonant 2nd Rt & Lt intercostal space parasternal line, impaired note on lower 1/3 sternum.
8. 8. Auscultation Apex: 1st heart sound of slightly reduced intensity, 2nd heart sound heard normal, pansystolic murmur , 2/6 , that radiate to axilla Tricuspid area: S1, S2 heard normal, no added sounds, no murmur Aortic area A2 heard normal no added sounds no murmur Pulmonary area P2 heard normal no added sounds no murmurs
9. 9. Chest EBAE no added sounds Abdomen No hepatomegaly, no spleenomegaly, no ascites.
10. 10. ECG: Sinus bradycardia, HR= 40 bpm, normal axis, scooping of ST segment I, Avl, V4-6 Echo: Mild LVH, calcific mitral annulus, sclerotic aortic valve, mild mitral regurgitation.
11. 11. Laboratory tests: ABG= PH: 7.38, Co2: 35, O2: 110, HCo3: 21, O2sat: 96% S.creatinine= 3.2 mg/dl S. urea= 119 mg/dl K = 4.4 mmol/l Ca= 8 Uric acid= 10.1 P = 4.1 INR= 1 S.albumin= 3.1 Bil= 0.7 HCV+ve Urine analysis: pus cells +ve Urine culture: E-coli
12. 12. Lanoxin level= 4.9 ng/dl
13. 13. Digoxin therapy and toxicity By : Alaa Atteya AboDonia
14. 14. More than 200 years with Digoxin therapy & toxicity
15. 15. Cardiac actions of digitalis glycosides have been recognized for centuries. The use of digoxin has decreased because of the availability of agents with greater potency and a wider therapeutic to toxic drug concentration range
16. 16. Electrophysiologic Actions Enhancing both central and peripheral vagal tone: Slowing of the sinus node discharge rate Shortening of atrial refractoriness Prolongation of AV nodal refractoriness Effects on the His-Purkinje system and ventricular muscle are minimal, except in toxic concentrations In studies of denervated hearts, little effect on AVnode and causes a mild increase in atrial refractoriness The characteristic ST and T wave abnormalities seen with digoxin use do not represent toxicity.
17. 17. Pharmacokinetics Oral dosing: the peak effect occurs in 4 to 6 hrs. Tablet forms are 60% to 75% absorbed Intravenously administered: some effect within minutes, with a peak effect occurring after 1.5 to 3 hours. Cholestyramine or antacids decreases absorption. The serum halflife is 36 to 48 hours Excreted unchanged by the kidneys
18. 18. INDICATIONS Orally to control the ventricular rate in chronic atrial fibrillation, At rest vagal tone predominates and rate controlled in 40-60% pateints But even with mild exertion marked increase in ventricular rate Rarely used as a single agent
19. 19. Acute rate control in AF ESC Guidelines 2010 Atrial Fibrillation In the acute setting, IV administration of digitalis or amiodarone is recommended to control the heart rate in pateints with AF and concomitant heart failure, or in the setting of hypotension .( I B )
20. 20. In heart failure ESC 2012 Guidelines of heart failure , Digoxin indications IIb B: May be considered to reduce the risk of HF hospitalization in patients with an EF 45% and persisting symptoms (NYHA class IIIV) despite treatment with a beta-blocker, ACE inhibitor (or ARB), and an MRA (or ARB). IIb B: May be considered to reduce the risk of HF hospitalization in patients in sinus rhythm with an EF 45% who are unable to tolerate a beta-blocker (ivabradine is an alternative in patients with a heart rate 70 b.p.m.). Patients should also receive an ACE inhibitor (or ARB) and an MRA
21. 21. DOSAGE Most patients require 0.125 to 0.25 mg/day as a single dialy dose As little as 0.125 mg every other day in renal impairment Young patients may require as much as 0.5 mg/day In acute loading doses of 0.5 to 1.0 mg, digoxin may be given intravenously or by mouth Serum digoxin levels for compliance & digitalis toxicity , but not routine if ventricular rate is controlled during atrial fibrillation and no symptoms of toxicity
22. 22. Digoxin Toxicity Narrow window between therapeutic and toxic concentrations Clinical picture: Headache, Generalized malaise Nausea and vomiting Altered color perception, halo vision More serious than these are digitalis-related arrhythmias, Bradycardias related to a markedly enhanced vagal effect (e.g., sinus bradycardia or arrest, AV node block) Tachyarrhythmias that may be caused by delayed afterdepolarization mediated triggered activity (e.g., atrial, junctional, and ventricular tachycardia) most common paroxysmal atrial tachycardia with block
23. 23. Forms of toxicity Acute: Accidental Intentsional Chronic: Therapeutic error Decreased elimination Drug interactions Condition increasing pateint sensitivity to digoxin
24. 24. Conditions increasing a patients sensitivity to digoxin toxicity Worsening renal function Advanced age Hypokalemia Hypothyroidism Amyloidosis Chronic lung disease
25. 25. Confirming diagnosis Plasma digoxin level should be measured at least 6 hours after the last dose since this is the time required for attainment of the steady state
26. 26. Management Stop Digoxin and Diuretics Decreasing absorption: Charcol, Cholestyramine ?? Gastric lavage (acute overdose) increases vagal tone and may precipitate arrhythmias, Consider pretreatment with atropine if performed. Proper hydration to optimize renal clearance Estimate serum potassium
27. 27. Management of dysrhythmias Depending on the presence or absence of: hemodynamic instability Nature of the arrhythmia Electrolyte disturbances
28. 28. Digoxin toxicity induced Bradyarrhythmias : Hemodynamically stable : Observation and discontinuation of the drug Hemodynamically unstable : Digibind Atropine (improves AV nodal conduction)(short acting) Cardiac pacing (used successfully, but induce arrhythmias)
29. 29. Digoxin toxicity induced supraventricular arrhythmias Hemodynamically stable: observation Short-acting beta blockers (eg, esmolol) may be helpful for supraventricular tachyarrhythmias with rapid ventricular rates, but advanced or complete atrioventricular (AV) block may be precipitated. If rate-related ischemia or hemodynamic instability, Digibind is the treatment of choice Calcium channel blockers are contraindicated because they may increase digoxin levels
30. 30. Premature ventricular contractions (PVCs), bigeminy, or trigeminy may be observed unless the patient is hemodynamically unstable, in which case lidocaine may be effective.
31. 31. Digoxin toxicity induced Ventricular tachycardia Responds best to Digibind Lidocaine and phenytoin may be useful because they depress the enhanced ventricular automaticity without slowing AV conduction Lidocaine : boluses of 100 mg & If successful, infusion 1-4 mg/min Phenytoin : May reverse digitalis-induced prolongation of AV nodal conduction Dissociate the inotropic and dysrhythmic action of digitalis Can terminate supraventricular dysrhythmias induced by digitalis Phenytoin administered in boluses of 100 mg every 5-10 minutes up to a loading dose of 15 mg/kg
32. 32. Direct-Current Electrical Cardioversion Relatively Contraindicated Performed only when absolutely necessary in the digitalis-toxic patient because life-threatening VT or VF can result, which can be very difficult to control.
33. 33. Correction of Hypokalemia Mild toxicty: potassium salts 5-7.5 g KCL Serious arrhythmias: 40 mEq of KCL in 500ml of G 5% glucose IV over 2-4 hours
34. 34. Role of Magnesium therapy As temporizing antiarrhythmic agent until fab available. Life saving when VT or VF IV magnesium sulfate, 2 g over 5 minutes Aside from successful replacement of intracellular magnesium, act as an indirect antagonist of digoxin at the supraphysiologic level After an initial bolus of 2 g intravenously, a maintenance infusion at 1-2 g/h is initiated. Monitor magnesium levels approximately every 2hours, The therapeutic goal between 4 and 5 mEq/L
35. 35. For hyperkalemia Calcium is not recommended to treat hyperkalemia, because ventricular tachycardia or ventricular fibrillation may be precipitated. Sodium bicarbonate and/or glucose and insulin are indicated. Digoxin-fab fragments for K+ > 5 mEq/L Kayexalate (0.5 g/kg PO) binding potassium and enterohepatically recycled digitalis. However, digoxin-induced hyperkalemia reflects an extracellular shift, not an increase in total body potassium
36. 36. AntiDigoxin Antibodies Digibind Indications: For severe toxicity Life threatening arrhythmias Hemodynamic instability Hyperkalemia > 5 Digoxin level more than 10 ng/ml Altered mental status Ingestion greater than 10 mg in adults (40 x 0.25 mg tablets) or greater than 0.3 mg/kg in children
37. 37. Dosing of Digibind: No. Vials= digoxin level (ng/ml) x Wt (Kg) / 100 1 vial of Digibind= 40 mg = neutralize 0.6 mg of digoxin
38. 38. Home message Donot prescribe lanoxin unless guideliness-indicated Narrow window between therapeutic and toxic concentrations Suspect toxicity in elderly, renally impaired pateints on lanoxin with (GIT+CNS+Vision+Rhythm) abnormalities
39. 39. Home message Management of lanoxin induced dysrhysmias Atropine and pacing for unstable bradyarrhythmias Lidocaine or phenytoin + Magnesium for VT, VF B-Blockers may induce advanced AV block Calcium channel blockers are contraindicated Importance of electrolyte imbalance correction Importance of hypokalemia correction Indications and dosing of digibind DC relative contraindication