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 Presented By:
Dr. Emad Ahmad
supervised by:
Dr. Mirella Halabi
INTRODUCTION:
- Digoxin poisoning is a potentially life-threatening intoxication.
- Patients can present with toxicity as a result of chronic therapy or acute overdose (doctor and family ??!!).
- Reported mortality ranges from 3% to 50 %.
- outcomes have clearly improved with the administration of Digoxin-specific antibody fragments to patients with severe toxicity
Mechanism of Action:
- Increases the influx of calcium ions from extracellular to intracellular cytoplasm by inhibition of Na and K ion movement across myocardial membranes.
- this increase in calcium ions results in a potentiation of the activity of the contractile heart muscle fibers and an increase in force of myocardial contraction.
- inhibits adenosine triphosphatase (ATPase).
- decreases conduction through S-A and A-V nodes.
INDICATION OF DIGOXIN:
Treatment of CHF( Congestive Heart Failure)
slows Ventricular rate in tachyarrhythmias such as:
- Atrial Fibrillation.
- Atrial Flutter.
- Supraventricular Tachycardia.
Total Digitalizing Dose:
- give one-half of the total digitalizing dose (TDD) in the initial dose, then give one-quarter of the TDD in each of two subsequent doses at 8- to 12-hour intervals.
- Obtain EKG 6 hours after each dose to assess potential toxicity.
Daily maintenance dose:
- divided every 12 hours in infants and children <10 years of age.
- Give once daily to children >10 years of age and adults
Oral:
- avoid concurrent administration (ie, administer digoxin 1 hour before or 2 hours after) with meals high in fiber or
- pectin that decrease oral absorption of digoxin.
Parenteral:
- Administer I.V. doses slowly over 5-10 minutes.
- avoid rapid I.V. infusion since this may result in systemic and coronary arteriolar vasoconstriction.
- I.M. route not usually recommended due to local irritation, pain, and tissue damage.
- from parenternal to oral dose: 25%
What are possible side effects of this medicine?
- Belly pain.
- Nausea or vomiting( Small frequent meals, frequent mouth care, or chewing sugar-free gum may help).
- Diarrhea.
- A faster, harmful heartbeat can rarely occur.
- A slower, harmful heartbeat can rarely occur.
CONTRAINDICATIONS:
- Hypersensitivity to Digoxin or digitalis preparations.
- ventricular fibrillation.
- A-V block.
- Idiopathic Hypertrophic Subaortic Stenosis.
- Constrictive Pericarditis.
WARNINGS:
-Use with extreme caution in patients with hypoxia, hypothyroidism, acute myocarditis, electrolyte disorders, acute MI.
DIGOXIN IN RENAL FAILURE:
STABILITY
I.V. solution compatibility: D5W, D10W, NS, do not mix with other drugs; store at room temperature; protect from light.
PHARMACODYNAMICS
Onset of action: Oral: 0.5-2 hours
I.V.: 5-30 minutes
Maximum effect: Oral: 2-8 hours
I.V.: 1-4 hours
Duration (adults): 3-4 days
DOSAGE FORMS:
-Injection, solution: 250 mcg/mL (1 mL, 2 mL) (contains alcohol 10% and propylene glycol 40%).
-Solution, oral: 50 mcg/mL (2.5 mL, 5 mL, 60 mL).
-Tablet: 125 mcg, 250 mcg.
MONITORING PARAMETERS
- Heart rate and rhythm, periodic EKG.
- K,Ca,Mg (especially in patients receiving diuretics).
- assess renal function (serum BUN, Scr) in order to adjust dose.
- obtain serum drug concentrations at least 8-12 hours after a dose.
REFERENCE RANGE
Therapeutic: 0.8-2 ng/mL (SI: 1.0-2.6 nmol/L).
Toxicity usually associated with levels >2 ng/mL.
- Digoxin toxicity can occur in a patient with any condition that either increases total body levels, or modifies cardiac sensitivity to the drug.
- Patients may present with acute or chronic toxicity.
- The history should determine the change, if any, there is an acute ingestion
There are a number of factors that can increase the sensitivity to digoxin and predispose to toxicity despite plasma levels at the upper limits of normal:
1-advanced age.
2-certain cardiac diseases: (active ischemia, myocarditis, cardiomyopathy, cardiac amyloidosis, cor pulmonale).
3- metabolic factors: hypokalemia, hypomagnesemia, hypoxemia, hypernatremia , hypercalcemia, and acid-base disturbances).
CLINICAL MANIFESTATIONS:
- Central nervous system: Drowsiness, fatigue, headache, lethargy, disorientation, dizziness, confusion, delirium, and occasionally hallucinations.
- Endocrine & metabolic: Hyperkalemia with acute toxicity.
- Gastrointestinal: Vomiting, nausea, anorexia, feeding intolerance, abdominal pain, diarrhea.
- Ocular: Blurred vision, , yellow or green vision, diplopia, photophobia, flashing lights.
- Cardiovascular: Sinus bradycardia, A-V block, S-A block, atrial or nodal ectopic beats, ventricular arrhythmias, atrial tachycardia with A-V block.
- mechanisms by which Digoxin promotes the development of arrhythmias are still incompletely understood.
- any arrhythmia can be seen with Digoxin toxicity.
- Bradycardia is the most frequently encountered vital sign abnormality.
- Tachyarrhythmias are less common.
- electrocardiographic manifestations depend in part upon age of patient and state of myocardium.
- patients with severe cardiac disease are more susceptible to ventricular ectopy.
- Hypotension may complicate severe toxicity.
Plasma Digoxin levels:
- plasma levels can be used to monitor both compliance and toxicity.
- Plasma digoxin levels should be measured at least six hours after the last dose.
- Measurements made sooner after ingestion may give values two to three times higher.
- Several factors (such as hypokalemia) can predispose to toxicity at levels below 2 ng/mL.
- On the other hand, some patients are asymptomatic despite clearly elevated levels (above 3 ng/mL)
Plasma Digoxin levels:
False positive results:
- in newborns.
- pregnant women.
- patients with chronic renal failure or hepatobiliary disease.
False negative results:
Patients patients who have ingested a non-digoxin cardiac glycoside, including foxglove and oleander, may have trivial digoxin levels.
Treatment:
- Digoxin is adsorbed effectively by activated charcoal (1gr/k) if ingestion has occurred within 6 to 8 hours repeated doses can be given.
- Management of electrolyte disorders:
-acute toxicity: hyperkalemia may be treated with the exception that calcium salts should not be administered.
- chronic toxicity: potassium should lowered with caution.
- Hypokalemia and hypomagnesemia should be treated.
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