CARDIAC GLYCOSIDES POISONING

By Rebeccah Barasa
MBchB IV umb/15-A/060
moderator:Dr C.Wafula(clinical pharmacologist)
Definition: Cardiac glycosides are organic compounds containing a
glycoside(sugar) and a common steroid nucleus that act on contractile
force of cardiac muscles.
Examples; Digoxin,Digitoxin,Lanatoside C,Ouabain,Deslanoside and
Gitaline.
Common:digoxin and digitoxin
Source;plants eg Digitalis lanata,skin of some toads and some butterflies.
Digoxin is one of the top toxins in the world because of its wide
availability,narrow therapeutic window and interactions with many
therapeutic drugs.
Digoxin is used is commonly used for treatment of atrial fibrillation
especially with co-existing congestive heart failure.
EPIDEMIOLOGY
Number of patients admitted with digoxin toxicity has remained stable although use of
digoxin fab(fragment antigen binding antidote) has increased.In US approximately 0.4%
patients are admitted,1% outpatients on digoxin toxicity,common in adult above
55years.prevalence is comparable in men and women.
MECHANISM OF POISONING
Direct effect
Digoxin inhibits cardiac Na/K+Atpase resulting in increased
concentration of intracellular Na+increased intracellular
Ca2+increased inotropy
It also leads to increase extracellular potassium.
In digoxin toxicity,excessive intracellular calcium can result in delayed
after depolarizations which may result in premature contractions and
dysrhythmias.
Electrophysiological effect:-at higher concentrations,cardiac
glycosides can increase automaticity and increase in symphathetic
tone leading to arrhythmias,
PATHOPHYSIOLOGY
1. Cardiac-arrhythmia-due to alterations in cardiac rate and rhythm
Decrease AV conduction leads to bradycardia and heart block(first,second and
third)
2.Arrhythmias can cause inadequate tissue perfusion leading to hypoxic seizures
and acute tubular necrosis
3.Hyperkalemia-it slows AV conduction adding to digoxin toxicity
4.GIT manifestations-digitalis preparations increases vagal stimulation and activates
chemoreceptor trigger zone resulting in nausea and vomiting ,abdominal pain and
anorexia.
5.Visual disturbances-color vision(yellow and green patches),scotomata,diplopia
AETIOLOGY
 Suicide gestures or homicidal toxicity
 Drug overdose—a dose < 5mg in adults is rarely to cause toxicity but >11mg
is fatal ,in paeds >4mg is fatal.
 Incorrect dosages-therapeutic serum digoxin concentration should be 0.9-
0.9ng/ml
 Risk factors—renal dysfunction, elderly, females, drug interactions
 Accidental exposure to plants containing cardiac glycosides
Clinical manifestations
Acute toxicity
-In young people due to acute overdose ,arrhythmias, especially
bradyarrhythmias ,nausea ,vomiting, abdominal pain and
hyperkalemia,anorexia,Av block
Chronic toxicity
Usually in old patients on digoxin treatment as a result of decreased
clearance of digoxin,declining renal function or drug-drug
interactions.includes nausea, vomiting,malaise, neurological
manifestations eg lethargy, fatigue,confusion and weakness.visual
disturbances ,hypokalemia and arrhythmias(tachyarrythmias)
LABORATORY INVESTIGATIONS
 Serum digoxin concentration 4-6hrs after ingestion
 Measure Na+,K+,Mg2+,Ca2+,blood urea nitrogen (BUN),creatinine levels,
Long term digoxin users have hypomagnesia secondary to diuretic usage
 ECG-shows any of the following
 Arrythmias, inverted T wave,peaked T wave(hyperkalemia) or Torsade de
pointes
 Normal lab values—a therapeutic serum digoxin concentration 0.8-
2.0ng/ml,potassium 3.5-5.5mEq/L
Diagnosis
The diagnosis of digoxin toxicity is primarily clinical based
on symptoms,ECG and potassium levels.
Because of narrow therapeutic window,patients can be
digoxin toxic with therapeutic levels,therefor elevated
digoxin levels alone does not translate to digoxin toxicity.
 DIFFERENTIAL DIAGNOSIS
 Renal failure
 Acute ischemia
 Neonates,pregnancy,subarachnoid hemorrhage,liver failure and
acromegaly have endogenous digoxin like substances that cause falsely
elevated digoxin concentrations
 MANAGEMENT POINTS
 Assessment and stabilization-ABC
 Determine if there are any indications for giving fab
 EMERGENCY MANAGEMENT
 Airway-endotracheal intubation
 Hyperkalemia-fab
SPECIFIC TREATMENT
 ABC
 Hydration with IV fluids, oxygenation and support of ventilator function
 Discontinue the drug
 Bradycardic-atropine 0.5mg IV
 Correct electrolyte imbalances,for example in hyperkalemia give insulin+glucose to shift
the K+ intracellularly.
 Administer activated charcoal or cholestyramine as adjuvant not as primary therapy
 Antiarrhythmias-incase of tachycardia give lidocaine,bradycardia atropine
 Fab(Digoxin specific fragment antigen binding antibodies) to life threatening
arrhythmias,evidence of end organ dysfunction,altered mental status.hyperkalemia
>5.5meq/L
 FAB
 One vial of fab binds 0.5mg of digoxin.
 Unknown concentration of digoxin use 10vials empirically for adults and
5vials for children.
 The following formular is used to calculate
 No of vials=serum digoxin conc(ng/ml) multiply by patient weight(kg)
divide by 100.
 Chronic toxicity without overt hemodynamic instability,consider partial
reversal in which half of the calculated reversal dosage is administered
 Acute ingestion,if the amount of digoxin is known ,the amount of vials to be
administere=amount of digoxin ingested in mg divide by 0.5
 EXPECTED RESPONSE TO TREATMENT
 Hyperkalemia due to glycoside toxicity improves after fab treatment.
 Dysrhythmias should correct over ensuring half hour
 If no change in hemodynamics after fab administration,such for alternative
etiologies
 REFRACTORY CASES
 In renal failure,recurrence of symptoms may occur after digoxin molecule
separates from fab fragments.
 This dissociation can occur several days after initial treatment and should
be treated with additional fab fragments
GI decontamination and enhanced elimination
First line treatment for acute ingestion is gastric lavage with repeated
dosing of activated charcoal to reduce absorption and interrupt
enterohepatic circulation.effective if ingestion has occurred within 6-
8hours.
Pretreatment with atropine recommended to decrease incidence of
AV block or bradycardia as a result increased vagal tone caused by
gastric lavage
 Cholestyramine
Is a binding resin,binds to the drug and breaks
enterohepatic circulation
Induced emesis with ipecac syrup not used due to
increased vagal tone
Whole bowel irrigation maybe useful
MONITORING PARAMETERS
i. Digoxin serum concentration
ii. electolytes concentration,especially potassium
iii. Signs of end organ hypoperfusion -Renal function-BUN,Creatinine levels
iv. Obtain a 12 lead electrocardiogram
PROGNOSIS
The prognosis for acute digoxin toxicity directly correlates with the mortality.
Without Fab,a k+ level of >5mEq/L is associated with a 50% mortality,>5.5mEq/L
is associated with a 100% mortality.
 POSTMORTEM RESULTS
 Blood samples taken from the heart(left ventricle), femoral artery ,gastric
contents and in contents of small intestines reveals high concentration of
digoxin 7-15ng/ml.
 Slight cardiac enlargement, moderate coronary atherosclerosis and
moderate congestion of liver and lung.
 Renal cortices thin and renal pelves dilated.
 Bladder with chalky urine
 Diffusely red mucosa of the stomach
 Odour of bitter almonds when opening the body cavities
REFERENCES:
Katzung Basic and clinical pharmacology 12th edition
Medscape
Https://digoxin toxicity.com
 THANK YOU.