Adverse Extra-Cardiac Effects of Selected Antiarrhythmic Drugs

Drug (Class)

Adverse Extra-Cardiac Effects and Toxicities

Quinidine (IA)

• GI disturbances in 30-50% of patients: diarrhea, nausea, vomiting

• Cinchonism

• Hypotension (due to alpha-adrenergic blocking activities)

• Can elevate serum digoxin concentrations, resulting in digitalis toxicity

• Hypersensitivity reactions: rashes, fever, angioneurotic edema, hepatitis

• Reversible thrombocytopenia

Procainamide (IA)

• Hypotension (due to ganglionic blocking activity)

• Long-term use results in a lupus-like syndrome in 15-30% of patients consisting of arthralgia and arthritis (pleuritis, pericarditis, parenchymal pulmonary disease also occur in some patients)

• GI symptoms in 10% of patients

• Adverse CNS effects: giddiness, psychosis, depression, hallucinations

• Hypersensitivity reactions: fever, agranulocytosis (can lead to fatal infections), Raynaud's syndrome, myalgias, skin rashes, digital vasculitis

Lidocaine (IB)

• Lowest incidence of toxicity of currently used antiarrhythmic drugs

• CNS depression: drowsiness, disorientation, slurred speech, respiratory depression, nausea

• CNS stimulation: tinnitus, muscle twitching, psychosis, seizures

• Concurrent use of tocainide or mexiletine can cause additive CNS toxicity, including seizures (seizures respond to i.v. diazepam)

Tocainide (IB)

Mexiletine (IB)

• GI effects: nausea, vomiting

• CNS effects: dizziness, disorientation, tremor

• Hematological effects (0.2%) with tocainide: agranulocytosis, bone marrow suppression, thrombocytopenia; can lead to death

• Concurrent use of either of these drugs and quinidine in combination may be effective at lower doses than either drug alone and thereby minimize adverse effects of both drugs

Flecainide (IC)

• CNS effects in 10-15% of patients: dizziness, tremor, agitation, headache, visual disturbances

• GI upset

Amiodarone (III)

• Although this drug is highly effective in treating many arrhythmias, its large number adverse effects limits its clinical use

• Adverse effects are common (more than 75% of patients receiving drug) and increase after a year of treatment; some toxicities result in death

• Half-life of 25-110 days can prolong toxicity

• Pulmonary toxicity and fibrosis (10-15%, can cause death in 10% of those affected); can be irreversible

• Constipation in 20% of patients)

• Hepatic dysfunction; can be irreversible

• Asymptomatic corneal deposits occur in all patients

• CNS effects (ataxia, dizziness, depression, nightmares, hallucinations)

• Hypothyroidism or hyperthyroidism (5% of patients)

• Cutaneous photosensitivity (25% of patients) and blue-grey discoloration of skin (less than 5% of patients)

• Peripheral neuropathy

• Substantial increases in LDL-cholesterol concentrations often seen; phospholipidosis

• Enhances the effect of warfarin and increases the serum concentrations of digoxin, quinidine, procainamide, flecainide, theophylline and other drugs

Digitalis (Misc.)

• Many adverse non-cardiac effects (anorexia, nausea, vomiting, diarrhea, abdominal pain, headache, confusion, abnormal vision)

• Adverse effects may indicate digitalis toxicity

Adenosine (Misc.)

• Short half-life in blood (less than 10 seconds) minimizes problems

• Causes hypotension, flushing in 20% of patients

• Transient dyspnea, chest discomfort (non-myocardial) in more than 10% of patients

• Metallic taste

• Headache, hypotension, nausea, paresthesias are less common