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- 1. By: Alaa Atteya AboDonia
- 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. 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. History of the present complain Presented to our internal
medicine clinic and was admitted to our hospital for workup
- 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. 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. 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. 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. Chest EBAE no added sounds Abdomen No hepatomegaly, no
spleenomegaly, no ascites.
- 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. 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. Lanoxin level= 4.9 ng/dl
- 13. Digoxin therapy and toxicity By : Alaa Atteya AboDonia
- 14. More than 200 years with Digoxin therapy &
toxicity
- 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. 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. 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. 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. 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. 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. 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. 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. Forms of toxicity Acute: Accidental Intentsional Chronic:
Therapeutic error Decreased elimination Drug interactions Condition
increasing pateint sensitivity to digoxin
- 24. Conditions increasing a patients sensitivity to digoxin
toxicity Worsening renal function Advanced age Hypokalemia
Hypothyroidism Amyloidosis Chronic lung disease
- 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. 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. Management of dysrhythmias Depending on the presence or
absence of: hemodynamic instability Nature of the arrhythmia
Electrolyte disturbances
- 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. 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. Premature ventricular contractions (PVCs), bigeminy, or
trigeminy may be observed unless the patient is hemodynamically
unstable, in which case lidocaine may be effective.
- 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. 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. 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. 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. 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. 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. 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. 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. 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