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Link to Problems for Discussion Antiarrhythmics


Class Drugs Action
Ia Quinidine Procainamide DisopyramideBlock fast sodium current. These also block repolarising potassium currents and hence lengthen action potential duration
Ib Lignocaine Mexiletine PhenytoinBlock fast sodium current. This slows rate of depolarisation and reduces conduction velocity. These shorten action potential duration
Ic Flecainide EncainideBlock fast sodium current with slow offset kinetics. Cause marked depression of depolarisation with little change in action potential duration.
II Beta-blockersBlock effects of catecholamines
III Amiodarone SotalolLengthen action potential duration by blocking potassium currents
IV Calcium channel blockersBlock inward calcium current particularly notable in AV node

Class 1c Antiarrhythmics


Diprafenone, Encainide *, Flecainide *, Indecainide, Lorcainide, Pilsicainide, Propafenone *, Recainam

These drugs are the most widely used drugs in this class and most information on both therapeutic use and overdose relates to these drugs. Others in the class are likely to have similar cardiac manifestations but other aspects of their toxicology are unknown.


Overdose with class 1C antiarrhythmic drugs is among the most serious poisoning caused by therapeutic substances. Marked ECG abnormalities, serious arrhythmias, cardiac arrest and death occur commonly and rapidly. The most important treatments are supportive care, gastrointestinal decontamination, and early and repeated doses of sodium bicarbonate to treat any arrhythmias.


Class 1C antiarrhythmic drugs, in common with all class 1 antiarrhythmics, block sodium channels in cardiomyocytes and cardiac conducting tissue. In therapeutic use, they block depolarisation and slow conduction more than class 1A - 1B antiarrhythmics. class 1B antiarrhythmics have rapid offset kinetics, thus the sodium channel is reactivated between contractions. In contrast, Class 1C antiarrhythmics have slow offset kinetics and cause complete blockade of any particular sodium channel for a much longer duration. They generally do not slow repolarisation in therapeutic use, however in overdose both prolonged JT intervals and torsade de pointes have been reported. See also mechanisms behind drug induced arrhythmias


These drugs have quite varied kinetics. Flecainide is well absorbed, has a high volume of distribution, and has significant hepatic and renal clearance. Renal clearance is enhanced in acidic urine, however, a systemic acidosis is likely to exacerbate cardiac toxicity and must be avoided. Propafenone is well absorbed but has low bioavailability due to presystemic metabolism. It also has significant renal and hepatic clearance. Encainide is well absorbed but has low bioavailability in extensive metabolisers (CYP2D6) but high bioavailability in poor metabolisers. Similarly, plasma concentrations, clearance, and half-life vary greatly with metaboliser status.


The major effect is on cardiac conduction. The ECG shows progressive prolongation of the QRS interval, often to well over 200 ms. QT prolongation often merely reflects QRS prolongation but JT prolongation also has been reported. Increased poisoning may lead to heart block, Torsade de pointes, other ventricular arrhythmias, ventricular fibrillation, and asystole. Cardiac arrest has been reported in nearly a quarter of all patients with flecainide overdose and all overdoses require active treatment and monitoring. Other effects include nausea, vomiting, sedation, seizures, and hypotension.


Blood concentrations

Conversion factor flecainide

  • mg/L x 2.41 = micromol/L
  • micromol/L x 0.414 = mg/L

Blood concentrations may be of prognostic significance though are unlikely to alter management. As the treatment is unaltered by their measurement, urgent blood tests are not warranted.


Patients should have a baseline ECG, repeated 6 hours later, and monitoring for at least 24 hours.


Electrolytes (sodium, potassium, magnesium, and bicarbonate) should be measured as low concentrations of any of these may exacerbate toxicity.


Class 1C antiarrhythmics should be considered (along with other drugs with membrane blocking effects) in patients with QRS prolongation and/or ventricular arrhythmias. In contrast with many of these drugs, These drugs are less sedating and have no anticholinergic effects. They are also not prescribed for psychiatric conditions. These drugs are usually only prescribed for people with a history of life-threatening arrhythmias and evidence for this (surgical scars (precordium, cubital fossa), pacemaker, Esc) should be sought.


Flecainide overdose has been well described. Experience with other drugs within this group is much more limited, but does not provide evidence that the clinical syndrome is substantially different for any of these drugs. Propafenone has weak beta blocking and calcium channel blocking effects, however, even in overdose, sodium channel blocking effects appear to dominate the clinical picture.


The QRS duration is the best indicator of the extent of sodium channel blockade. Life-threatening arrhythmias have generally been reported in individuals with grossly prolonged QRS complexes (>160 ms). Patients with QRS complexes greater than this or any arrhythmia should receive sodium bicarbonate.



Supportive treatment includes maintenance of the airway and ventilation, ensuring IV access and IV fluids (saline).

GI Decontamination

Gastric lavage should be considered in all patients who present within 1 hour after ingesting more than twice the recommended daily dose. Atropine should be given prior to lavage to prevent heart block or worsening bradycardia from the vagal stimulation. Activated charcoal in a standard dose should be given to patients who present within 1-2 hours.

Elimination enhancement

Haemoperfusion has been tried in flecainide overdose, although it is unlikely to be helpful as flecainide has a very large volume of distribution (about 9 L/kg). No dramatic clinical response or sustained change in plasma concentrations has been observed.

Treatment of specific complications


It is often very difficult to distinguish whether the patient is having a supraventricular arrhythmia with aberrant conduction or primary ventricular tachycardia. Most arrhythmias, especially if they are associated with low output, should be treated in a standard cardiac arrest protocol manner. The main difference is the requirement for early and large doses of NaHCO3 and the avoidance of drugs that may exacerbate toxicity.


Treatment with plasma alkalinisation to a pH of 7.5 using sodium bicarbonate (to alter both pH and sodium) or hyperventilation has been useful for arrhythmias induced by many sodium-channel blocking drugs. A number of case reports and animal studies suggest class IC antiarrhythmics also may respond. All other treatments are of questionable efficacy and safety and therefore controversial. Initial treatment is normally with sufficient IV NaHCO3 to produce a pH of 7.5 to 7.55. Following the rapid correction of pH to 7.5 by IV NaHCO3, the patient is usually maintained at this pH by mild hyperventilation. Alkalosis may cause a decrease in some free drug concentrations by increasing protein binding however this explanation is unconvincing for flecainide which has quite a low extent of protein binding. More likely, alkalosis affects the partitioning of antiarrhythmics between the cell membrane and the Na+ channel binding site and thus decreases Na+ channel blockade. Hypertonic saline alone also improves cardiac conduction.

Further drug treatment of arrhythmias

All class 1A antiarrhythmic drugs are contraindicated and lignocaine and phenytoin (class 1B drugs), while they may be used, may still exacerbate Na+ channel blockade and potentially exacerbate arrhythmias (e.g. convert VT into asystole). Magnesium is normally the drug of choice for treating torsade de pointes and is used for refractory arrhythmias in other settings. However, its calcium channel blocking activity may aggravate the hypotension and heart block that can complicate these poisonings. For this reason, isoprenaline or overdrive pacing should be preferred. Second or third degree heart block should be treated with atropine, bicarbonate and isoprenaline followed by a pacemaker.


Seizures should be treated with diazepam 5-20 mg IV followed by phenobarbitone 15 mg/kg IV if seizures continue.


The mortality of overdose with these drugs, even in hospital, is relatively high (>10%). Patients should be observed until ECG changes have resolved. Long-term sequelae have not been reported, although there is one report of persisting ECG changes. No follow up is required after resolution of the clinical signs - ECG findings unless the patient has been profoundly hypotensive or had a prolonged cardiac arrest.


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