Antidysrhythmic Toxicity Clinical Presentation
- Author: Nidhish Sasi, MD; Chief Editor: Asim Tarabar, MD more...
As in the case of any patient with suspected or known acute poisoning, attempt to obtain the following:
Original medication containers
The number of pills that may have been ingested
Approximate time of ingestion
A report of any potential co-ingestants
Family members or emergency medical services personnel should bring all the patient’s medications to the emergency department to help the clinician determine the source of toxic manifestations. Eliciting a history of co-ingestants is important because these can obscure the clinical picture.
In patients with prescribed antidysrhythmic agents, attempt to differentiate manifestations of primary disease from possible toxic effects of the drug by asking the following questions:
What were the indications for starting the drug?
If the patient does not know, will a call to the prescribing physician or a review of the medical record help?
How long has the patient been taking this drug?
How do the patient's symptoms correlate with the initiation of drug therapy?
Is the patient compliant with the drug therapy?
Has the patient taken any extra doses?
Has the patient added any new drugs recently?
Is the patient taking any nonprescription drugs?
Adverse Effects of Individual Agents Unrelated to Cardiac Conduction
The anticholinergic property of disopyramide leads to the following adverse effects:
Urinary hesitancy or retention
Disopyramide may also cause headache, muscle weakness, nausea, and fatigue. Patients with preexisting ventricular dysfunction or on beta blockade may report symptoms of heart failure, including dyspnea, edema, and decreased exercise tolerance. Disopyramide is also known to cause hypoglycemia, through unclear mechanisms.
Adverse effects that patients may report include gastrointestinal (GI) symptoms such as nausea, vomiting, and diarrhea; bitter taste; and neuropsyciatric symptoms such as headache, insomnia, dizziness, psychosis, hallucinations, and depression.
Long-term use of procainamide is associated with the development of antinuclear antibodies and drug-induced systemic lupus erythematosus (SLE) syndrome characterized by arthralgias, myalgias, rash, fever, vasculitis and Raynaud phenomenon. Unlike idiopathic SLE, which affects women more than men, drug-induced SLE has no predilection for either sex. Clinically, drug-induced SLE may also be differentiated from idiopathic SLE by the lack of renal and central nervous system (CNS) involvement.
Procainamide's ganglion-blocking properties may lead to periperal vasodilation and systemic hypotension. Rarely, blood dyscrasia may develop; these patients may present with gingival or GI bleeding, bruising, or fever and sore throat.[17, 18, 19]
Quinidine toxicity manifests primarly through GI, neurologic and cardiovascular symptoms. Cinchonism, a syndrome characterized by GI symptoms (abdominal cramping, nausea, vomiting, and diarrhea), tinnitus, and altered mental status may occur in both chronic and acute toxicity. Quinidine can cause immune-mediated hematalogic reactions such as rash, fever, anaphylaxis, hemolytic anemia, thrombocytopenia, and leukopenia. Rarely, quindine can be associated with a procainamide-like drug-induced SLE.
Patients on quinidine may report neuroglycopenic or adrenergic symptoms of hypoglycemia, as the drug acts on potassium channels in the pancreatic islet cells. Like procainamide and disppyramide, quinidine can cause anticholinergic symptoms such as dry mouth, visual blurring, or urinary retention. Quinidine has alpha-adrenergic antagonistic effects that may cause peripheral vasodilation, hypotension, and syncope.[20, 21]
Lidocaine toxicity predominantly involves CNS effects. Mild-to-moderate lidocaine toxicity may result in the following:
Severe lidocaine toxicity may result in seizures or coma.
Patients may report neurotoxic adverse effects similar to those that occur with lidocaine. Patients may also report nausea and vomiting.
Flecainide has generally nonfatal extracardiac effects that are promarily CNS in nature. These include visual blurriness, nausea, dizziness, confusion, and headache. Severe CNS toxicity, such as seizures, paranoid psychosis, hallucinations, and dyarthria, may occur, especially in patients with renal failure. An adverse effect of flecainide is worsening of congestive heart failure; these patients may report increased dyspnea on exertion, lethargy, and peripheral edema. Patients with cardiomyopathy may present in cardiac arrest from dysrhythmia.
Patients with preexisting systolic dysfunction may report symptoms suggestive of worsening heart failure, such as dyspnea and edema. Common adverse effects include alteration in taste, blurred vision, and dizziness. GI adverse effects of nausea, vomiting, and constipation are also reported. Asthmatic patients may report worsening symptoms, owing to the weak beta-blocking effects of propafenone. CNS adverse effects, such as dizziness, nausea, unusual taste, and blurred vision, are often dose dependent.
Propafenone may lead to agranulocytosis leading to immunosuppresion. Rarely, rash or SLE-like symptoms may occur.
Beta-blockers are class II antidysrhythmics. Complications from these drugs are covered in Beta-Blocker Toxicity.
Amiodarone has a number of extracardiac adverse effects, involving the lungs, thyroid, liver, CNS, and skin. Rapid intravenous amiodarone infusion may cause hypotension due the solvent base in which it is dissolved, or excipients such as benzyl alcohol or polysorbate 80. Aqueous solvent bases or formulations with cyclodextrin instead of benzoyl alcohol or polysorbate 80 have been found to not cause this reaction. Rapid infusion may also cause bradyarrhythmias and asystole. Otherwise, toxicity from amiodarone is generally attributed to prolonged use.[22, 23]
Amiodarone-induced pulmonary toxicity is the adverse effect of greatest concern. Suspected mechanisms of amiodarone lung toxicity include immunologic effects and direct cytotoxicity.[24, 25]
Pulmonary toxicity from amiodarone may manifest as pulmonary fibrosis, chronic interstitial pneumonitis, bronchiolitis obliterans, a solitary lung mass, or pleural effusion. Patients may report cough, fever, hemoptysis, malaise, dyspnea, weight loss, and occasionally pleuritis. The most worrisome presentation involves acute diffuse pneumonitis and respiratory failure resembling acute respiratory distress syndrome (ARDS), which may occur in patients with underlying lung disease and high oxygen requirements.
Other adverse effects of amiodarone include the following[26, 27] :
Thyroid: Symptoms suggestive of hyperthyroidism or hypothyroidism
Hepatotoxicity leading to cirrhosis (uncommon)
Dermatologic: Photosensitivity, bluish skin discoloration
Ophthalmologic: Vision loss from corneal deposition, optic neuropathy, or optic neuritis
Light-headedness from bradycardia or hypotension (rare)
CNS: Clumsiness, dizziness, tremulousness, sensation changes, cognitive difficulty, or sleep disturbances
Patients taking dronedarone may report nausea, diarrhea, and abdominal pain. A minority of patients may develop rash. Patients may report light-headedness or syncope related to bradycardia. Patients may report new or worsening heart failure symptoms. Dronedarone is contraindicated in patients with severe or worsening heart failure.
Unlike amiodarone, dronedarone is not typically associated with thyroid, neurologic, or ocular toxicity. Rare cases of pulmonary toxicity have been reported, and patients may report increasing shortness of breath or cough.
Patients may report palpitations, chest pain, light-headedness, fatigue, insomnia, headhche, dyspnea, or weakness. Patients with reactive airway disease may develop shortness of breath and wheezing. Sotalol may also cause GI symptoms such as mild diarrhea, nausea, or vomiting.
Headache occurs in a minority of patients.
The most common adverse effects that patients report are headache, chest pain, and light-headedness.
Calcium channel blockers
Complications from these class IV drugs are covered in Calcium Channel Blocker Toxicity.
Transient adverse effects are common and include headache, flushing, chest pressure, and dyspnea. These generally resolve quickly without any intervention.
Physical examination and electrocardiography findings
Cardiotoxicity includes negative inotropic effects through its blockade of myocardial calcium channels, PR prolongation, and QTc prolongation that may progress to torsade de pointes. CNS and anticholingeric effects may include mydriasis, urinary retention, dry skin, dry mucus membranes, increased ocular pressure with worsening vision and pain in glaucoma. CNS effects may include confusion and hallucinations. Other adverse effects include signs of worsening heart failure such as increased jugular venous distention (JVD), peripheral edema, and rales.
Acute cardiotoxicity may result in any of the following:
Prolongation of the corrected QT (QTc) interval
Torsade de pointes
Left ventricular dysfunction
Premature ventricular contractions
Atrioventricular (AV) block in patients with preexisting AV conduction abnormalities
Significant systemic hypotension due to vasodilation or dysrhythmia
Drug-induced lupus findings in patients on long-term therapy include morbilliform and malar rash, joint swelling with pain and restricted range of motion, as well as respiratory symptoms related to pleuritis.
Other neurologic acute symptoms may include seizures and psychosis. An allergic response may provoke fever. Physical signs from blood dyscrasias include ecchymosis, petechiae, purpura, pharyngitis, lymphadenopathy, and fever.
Cardiotoxicity causes hypotension, QRS widening, QTc prolongation, and PR prolongation.
Hematologic and immune-mediated toxicity may result in fever, bruising, rash, and respiratory symptoms.
CNS toxicity causes vision changes, seizures, lethargy, coma, and central apnea.
Lidocaine rapidly enters the CNS; a common initial sign of severe CNS toxicity is seizures. Seizures can be followed by coma and respiratory arrest. Other signs of CNS toxicity include somnolence and muscle fasciculations. Tremor may be the first sign of toxicity. Patients may become confused or show personality changes.
Cardiotoxicity may result in sinus arrest, atrioventricular block, hypotension, and cardiac arrest; prolongation of PR, QRS, and QT interval can occur in severe overdose.
CNS toxicity causes seizures, lethargy, confusion, and coma.
Cardiotoxicity can result in bradycardia, atrioventricular nodal block, torsades de pointes, ventricular fibrillation, hypotension, and cardiovascular collapse.
CNS toxicity may present as seizures, altered mentation, and stroke-like symptoms.
Cardiotoxicity (see image below) results in widening of QRS complexes (50% or greater increase), PR prolongation (30% or greater increase) leading to first- or second-degree heart block, QTc prolongation (15% or greater increase), bradycardia, AV block, ventricular fibrillation, and hypotension. Ventricular depolarization may be prolonged, increasing risk of torsade de pointes.
Flecainide may cause ST elevation in lead V1 characteristic of Brugada syndrome (and is used to assist diagnosis of patients suspected of having Brugada syndrome). A 1:1 atrioventricular conduction may occur during treatment of atrial flutter if the patient is not already on AV nodal blockers.[31, 7]
CNS toxicity results in seizures. Ataxia has been reported.
Cardiotoxicity causes widening of the QRS complex and sinus bradycardia. The negative inotropic effect may lead to systemic hypotension and overt heart failure.
Cardiac effects include QTc prolongation, PR prolongation, sinus bradycardia, ventricular dysrhythmias, torsade de pointes, AVblock, and hypotension. Torsade de pointes is an extremely uncommon complication with amiodarone, compared with other antiarrythmics that prolong the QTc interval, probably because of amiodarone's other mechanisms of action.
Jaundice may occur with hepatotoxicity and intrahepatic cholestasis.
Physical exam abnormalities of hyperthyroidisms or hypothyroidism may be evident.
Rash with bluish discoloration or increased photosensitivity and sunburn may occur.
CNS toxicity may be observed on exam, with hyperrefllexia, tremor, gait ataxia, confusion, and sensory changes associated with peripheral neuropathy. Tremor and hyperreflexia may also be a manifestation of amiodarone-induced thyrotoxicosis.
Pulmonary toxicity may manifest as crackles or rales without clubbing.
Findings in patients with adverse effects include the following:
Cardiac effects include bradycardia, QTc prolongation, and hypotension. Torsade de pointes has not been reported.
Pulmonary toxicity may mainfest crackles or rales without clubbing.
Liver dysfunction may result in jaundice or other signs of hepatic failure.
Cardiac effects can include significant bradycardia, AV block, hypotension, QTc prolongation, and ventricular arrhythmias (eg, torsades de pointes). Long-term use of sotalol is associated with a 2.5% risk of torsades de pointes ; consider torsades as a possible event for patients who present with a history of syncope.
Patients receiving an infusion of ibutilide may become bradycardic, hypotensive, or develop torsade de pointes. Toxicity from overdose is not reported.
Cardiac effects include QTc prolongation and torsade de pointes, as well as ventricular fibrillation.
In addition to the transient asystole that is the treatment goal, patients may develop bradycardia, AV block, or sinus arrest. Atrial fibrillation may be induced.
Rarely, bronchospasm may occur, especially in patients with underlying reactive airway disease.
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