Antiarrhythmic
pharmacology.

Parent half-life is about 3–4 hours with normal renal function. Hepatic acetylation forms active NAPA; acetylator status changes the parent/metabolite balance. Both require renal clearance, and NAPA can accumulate when kidney function falls, adding repolarization prolongation.

Avoid stacking QT-prolonging antiarrhythmics. Other sodium-channel blockers add conduction slowing; negative inotropes and vasodilators can compound hypotension.

Continuous ECG and blood pressure during loading. Stop for hypotension, QRS widening >50% from baseline, rhythm suppression, or the protocol maximum. Check baseline QT, renal function, potassium, magnesium, and heart-failure status.

Sodium-channel block can widen QRS and impair conduction. Procainamide and NAPA can prolong QT and promote torsades, especially when renal impairment increases exposure.

After an IV bolus, elimination half-life is usually 1.5–2 hours. Hepatic blood flow and CYP1A2/3A4 metabolism govern clearance. Low-output states and prolonged infusion increase exposure; active metabolites can accumulate, particularly when renal function is impaired.

Cimetidine and beta-blockers can reduce clearance; CYP inhibitors and amiodarone can increase exposure. Other local anesthetics or sodium-channel blockers add neurologic and conduction toxicity.

Follow rhythm, blood pressure, mental status, and infusion duration. Perioral numbness, tinnitus, confusion, tremor, or seizures suggest toxicity; do not wait for QRS widening. Sedation can conceal these warnings.

Low torsadogenic risk, since it shortens rather than prolongs the action potential; its signature harm is CNS excitation and seizures, and at high levels myocardial depression with bradyasystole, rather than QT-driven torsades.

Oral bioavailability is about 90%; peak concentrations occur in 2–3 hours and half-life is usually 10–12 hours. CYP2D6 and CYP1A2 provide most clearance. Liver disease can markedly prolong half-life; relatively little drug is excreted unchanged in urine.

CYP1A2 inhibition by fluvoxamine and CYP2D6 inhibition by quinidine can raise exposure. Enzyme inducers such as rifampin can lower it. Mexiletine can reduce theophylline clearance; review that combination rather than treating all interactions as QT interactions.

Track ventricular-arrhythmia burden, adherence, GI intolerance, tremor, dizziness, and ataxia. Reassess after hepatic deterioration or an interacting drug. Consider concentrations for suspected toxicity or difficult interactions, not as a substitute for clinical assessment.

QT-mediated torsades is not its characteristic toxicity, but existing ventricular arrhythmias can worsen. GI and neurologic adverse effects are common; conduction disturbance, hypotension and serious ventricular arrhythmias are also possible. Do not assume CNS symptoms must appear first.

Half-life is variable, about 12–27 hours; steady state commonly takes 3–5 days. Both renal elimination and hepatic metabolism matter. Kidney dysfunction can prolong exposure substantially, and dialysis removes little drug.

CYP2D6 inhibitors such as quinidine raise exposure; amiodarone also increases concentrations and requires a prescribing adjustment. Other sodium-channel blockers and negative inotropes compound conduction slowing and contractile effects.

Compare PR and QRS with baseline, review renal function and interacting drugs, and reassess new exertional symptoms or rate-related widening. Pill-in-the-pocket use requires an appropriate substrate, AV-nodal protection, and prior monitored testing—not an untested first home dose.

Rate-related QRS widening, incessant VT or flutter with 1:1 conduction, and excess mortality demonstrated with encainide/flecainide in post-MI ectopy suppression.

Hepatic first-pass metabolism is saturable, so exposure is nonlinear. Half-life is roughly 2–10 hours in extensive metabolizers and 10–32 hours in poor metabolizers. CYP2D6, CYP3A4, and CYP1A2 contribute; hepatic dysfunction increases exposure.

Avoid simultaneous CYP2D6 inhibition—or poor-metabolizer status—and CYP3A4 inhibition: the combination can markedly increase exposure. Propafenone raises digoxin, warfarin, and metoprolol exposure; check concentrations, INR, and bradycardia risk as appropriate.

Baseline and follow-up ECG for PR/QRS widening, bradycardia, and organized flutter. Confirm the Class Ic substrate restrictions. For pill-in-the-pocket use, establish safety in a monitored setting and provide an AV-nodal-blocking plan.

It can organize AF into flutter with dangerous 1:1 AV conduction. AV-nodal protection reduces this risk but does not guarantee safety. Sodium-channel block can also provoke ventricular arrhythmias in an unsuitable substrate.

Red-cell esterases hydrolyze the parent drug; elimination half-life is about 9 minutes. Renal failure mainly prolongs the inactive acid metabolite rather than the parent. Hemodynamic recovery after stopping is not instantaneous.

Avoid close-proximity IV verapamil because severe cardiodepression and cardiac arrest have occurred. Other AV-nodal blockers, negative inotropes, and vasodilators increase bradycardia or hypotension risk.

Monitor blood pressure, rhythm, perfusion, AV conduction, and bronchospasm throughout titration. Stop or reduce for hypotension, severe bradycardia, or impending cardiac failure. A short half-life does not make use in cardiogenic shock or decompensated heart failure safe.

Not proarrhythmic through repolarization; the hazards are hemodynamic, bradyasystolic pauses and hypotension when stacked on other AV-nodal blockers, and dangerous rate acceleration if given for pre-excited AF.

Primarily hepatically metabolized by CYP2D6. Typical half-life is 3–4 hours, but can reach 7–9 hours in poor metabolizers. Immediate-release tartrate and extended-release succinate have different release profiles; they are not interchangeable scheduling instructions.

Quinidine, fluoxetine, paroxetine, and other CYP2D6 inhibitors can increase exposure. Diltiazem, verapamil, digoxin, and other nodal agents add bradycardia or AV block.

Follow heart rate, blood pressure, perfusion, conduction, and bronchospasm. Reconcile the formulation and dosing schedule during transitions. Do not confuse acute rate control with the evidence-based extended-release formulation used for chronic HFrEF treatment.

Not QT-prolonging and not torsadogenic; its signature harms are bradycardia, AV block, and sinus arrest, dangerous rate acceleration in pre-excited AF, and rebound tachyarrhythmia or ischemia after abrupt withdrawal.

Extensive tissue distribution produces a very long and variable terminal half-life—often weeks to months. The active metabolite desethylamiodarone also persists. Stopping an infusion or tablet does not promptly eliminate interaction or organ-toxicity risk.

Inhibition of CYP pathways and P-glycoprotein raises warfarin and digoxin exposure. Plan INR surveillance and concentration/clinical monitoring with prescribing adjustments. Other nodal blockers add bradycardia; additional QT-active agents still require scrutiny.

Acute use: ECG, pressure, and perfusion. Chronic use: baseline and periodic thyroid/liver assessment, baseline chest imaging, and investigation of new cough or dyspnea. Evaluate visual symptoms rather than assuming a routine eye exam detects every toxicity.

Lower torsades risk than pure IKr blockers despite QT prolongation, but bradycardia and conduction block occur, and IV boluses cause hypotension.

Half-life averages about 12 hours with normal kidney function. Sotalol is not meaningfully metabolized and is excreted unchanged renally. Use the product's creatinine-clearance dosing method; a new AKI can turn a stable regimen into an accumulating QT-active exposure.

Other QT-prolonging agents increase torsades risk. Potassium-wasting diuretics and diarrhea worsen electrolyte risk; other beta-blockers or nodal agents add bradycardia. Review each new prescription and acute illness.

Oral initiation or reinitiation requires monitored care, generally at least 3 days or until steady state under the label protocol. A QT of ≥500 ms requires dose reduction, a longer interval, or discontinuation. Track creatinine clearance, potassium, magnesium, rate, and pauses; AF initiation has additional baseline QT restrictions.

Torsades de pointes is the signature: reverse-use-dependent, clustered early after starting or up-titrating, and potentiated by bradycardia, hypokalemia, hypomagnesemia, renal accumulation, and female sex. Sinus bradycardia and AV block come from the beta-block.

Half-life is approximately 10 hours. Most elimination is renal, including active cation secretion; CYP3A4 metabolism is a smaller pathway. Dose selection uses calculated creatinine clearance, then protocol-directed QT assessment.

Contraindicated combinations include cimetidine, trimethoprim—with or without sulfamethoxazole—ketoconazole, verapamil, and hydrochlorothiazide. Additional renal cation-transport inhibitors must also be excluded. These restrictions do not all share one mechanism; use the actual label interaction list.

Initiation/reinitiation requires continuous ECG for at least 3 days and at least 12 hours after conversion, whichever is longer. Baseline QT/QTc and creatinine-clearance exclusions apply; post-dose QT changes drive adjustment or stopping. Use QT rather than QTc when heart rate is below 60 under the label protocol.

Torsades de pointes, characteristically early and clustered in the first few doses, driven by concentration, bradycardia (reverse use-dependence), hypokalemia, and renal accumulation. This is why initiation is a monitored, protocolized event rather than an outpatient start.

Half-life is about 13–19 hours; take with meals because food increases absorption. CYP3A4 metabolism forms an active metabolite. Inhibition of tubular creatinine secretion can cause a small early plateauing rise, but does not explain every creatinine increase.

Avoid strong CYP3A inhibitors and inducers. P-glycoprotein inhibition raises digoxin and dabigatran exposure; renal function and the specific anticoagulant label determine management. Nodal blockers add bradycardia. Review statin and CYP2D6-substrate exposure.

Assess rhythm at least every 3 months; permanent AF requires discontinuation rather than indefinite continuation. Watch for worsening HF, hepatic injury, QT prolongation, and renal dysfunction. The expected small creatinine rise usually plateaus within about 7 days; a larger or progressive rise warrants evaluation for real AKI.

Modest QT prolongation with a low torsades rate relative to dofetilide and sotalol, so its danger is not primarily electrical. The real proarrhythmic and mortality hazard emerges as HF decompensation in the wrong substrate, along with bradycardia when layered on other AV-nodal blockers.

IV administration; average elimination half-life is about 6 hours, with substantial variability. Repolarization effects and torsades risk outlast the short infusion, so completion of administration is not completion of observation.

Correct potassium and magnesium first. Avoid concomitant QT-active Class Ia/III agents; the label prohibits administering these during or within 4 hours after ibutilide and describes pre-infusion washout in trials.

Continuous ECG for at least 4 hours after infusion; continue beyond that if QTc has not returned to baseline, and longer if arrhythmia occurs. Keep resuscitation capability available. Check QT, electrolytes and ventricular function before selection.

Torsades in a few percent—usually within the monitoring window—hence the mandatory post-dose observation.

Hepatic metabolism and drug interactions influence exposure. IV titration is useful, but bolus effects cannot be immediately recalled. Oral immediate- and extended-release products require formulation-specific transition planning.

Other beta-blockers, digoxin, or nodal agents add bradycardia/AV block. CYP3A4 inhibition can increase exposure to substrates such as midazolam; review sedation, statins, and immunosuppressants rather than checking only the rhythm medications.

Monitor rate, pressure, perfusion, and AV conduction. Establish that AF is not pre-excited and that systolic function supports use; reassess after a bolus before adding another nodal blocker.

Not proarrhythmic in the usual sense, but dangerous rate acceleration in pre-excited AF and bradyasystole when stacked with other AV-nodal blockers.

Extensive hepatic metabolism and oral first-pass handling make exposure formulation-dependent. IV hemodynamic effects require close monitoring; significant liver dysfunction can prolong handling.

Do not give IV verapamil and IV beta-blockers within close proximity: additive AV block and negative inotropy can be severe. Digoxin exposure may rise; review concentration and clinical findings. CYP3A4/P-gp interactions require a broader medication review.

Follow ECG, blood pressure, and perfusion. Exclude pre-excited AF and avoid empiric treatment of an undifferentiated wide-complex tachycardia. A selected verapamil-sensitive fascicular VT diagnosis is a specialist exception, not a general WCT rule.

Not proarrhythmic in the QT or repolarization sense; the signature harms are bradyasystole and high-grade AV block (worst when stacked with other AV-nodal blockers), profound hypotension, and lethal ventricular-rate acceleration in pre-excited AF.

Blood and endothelial uptake produces a half-life of less than 10 seconds. Renal and hepatic failure do not determine its usual dosing clearance. Delivery through a patent proximal IV with an immediate flush is central to effect.

Methylxanthines such as theophylline and caffeine antagonize the effect; dipyridamole potentiates it. Carbamazepine can increase AV block. Transplant and central-line circumstances require protocol-specific caution.

Record the ECG continuously through administration. Transient AV block may terminate AVNRT/AVRT or reveal atrial flutter without terminating it. Have resuscitation capability and counsel about brief flushing, chest discomfort, and dyspnea.

Transient AV block and pauses are common, but prolonged asystole and serious ventricular arrhythmias have been reported. AF can occur and is especially hazardous with an accessory pathway. Keep continuous ECG recording and immediate resuscitation capability; a short half-life is not a safety guarantee.

Magnesium is not metabolized and is eliminated by the kidneys. Repeated administration or ongoing infusion in renal dysfunction increases accumulation risk; a normal pretreatment level does not exclude its role in torsades treatment.

Potentiates nondepolarizing neuromuscular blockade. Magnesium depletion can make hypokalemia refractory; correct both when deficient rather than assuming every low potassium requires magnesium.

Follow rhythm, pressure, respiratory status, renal function, and magnesium when repeated or prolonged therapy is used. Diminished reflexes can warn of toxicity, but sedation and neuromuscular blockade limit the exam. Do not rely on a reflex check alone.

Essentially non-proarrhythmic; it does not provoke tachyarrhythmia. The signature harm runs the other way, toward bradyarrhythmia, high-grade AV block, and asystole from hypermagnesemia.

Distribution takes roughly 6–8 hours. Half-life is 1.5–2 days with normal renal function and can reach 3.5–5 days in anuria. The large distribution volume makes dialysis ineffective for removal.

Amiodarone, dronedarone, verapamil, and quinidine can raise exposure; plan prescribing adjustments and monitoring. Potassium depletion increases sensitivity to toxicity; other AV-nodal blockers add bradycardia or block.

Obtain a level just before the next dose or at least 6 hours after the last dose. Interpret it with timing, indication, renal function, electrolytes, ECG, and symptoms. An early post-load concentration can be misleading; toxicity can occur without a strikingly high measured level.

Its signature is digitalis toxicity: the paradoxical combination of enhanced automaticity from calcium-overload triggered activity with AV-nodal block. Watch for paroxysmal atrial tachycardia with block, bidirectional ventricular tachycardia, accelerated junctional rhythms, and a regularized ventricular response in AF.

Rapid tissue metabolism and uptake produce a short effect during IV infusion. Titrate to a specified rhythm/perfusion objective with continuous monitoring rather than assuming a higher rate is always better.

Avoid simultaneous epinephrine: combined catecholamine effects can provoke serious arrhythmias. Beta-blockers blunt the response; other sympathomimetics increase ischemic and arrhythmic risk.

Monitor rhythm, rate, pressure, ischemic symptoms/ST changes, and ventricular ectopy. Selected acquired pause-dependent torsades and Brugada electrical-storm uses are specialist-directed and off-label; the US label lists ventricular arrhythmias and angina as contraindications.

Its signature is demand ischemia and provoked ventricular ectopy in coronary disease, and precipitation or acceleration of catecholamine-sensitive VT (CPVT, adrenergic LQTS). Sinus tachycardia and rising myocardial oxygen demand are expected, not incidental.

IV onset is rapid; systemic elimination is much slower than the initial heart-rate response and can be prolonged in older adults. CNS penetration contributes to delirium and other antimuscarinic effects.

Other anticholinergics increase urinary retention, delirium, and related adverse effects. Bradycardia from beta-blocker or calcium-channel-blocker poisoning may require toxin-specific treatment even if atropine provides temporary improvement.

Assess perfusion and ECG response without delaying pacing when high-grade block or instability is present. A poor response is not a definitive localization test. Watch for ischemia from excessive tachycardia and antimuscarinic toxicity.

Not a repolarization proarrhythmic, but it can provoke sinus tachycardia, precipitate or worsen ischemia by raising myocardial demand, and, in infranodal block, drop the ventricular rate rather than raise it.