Drug-Induced Arrhythmias

藥物引起心律問題種類：

1. prolong the QT interval
2. provoke torsades de pointes (TdP)
3. bradyarrhythmias 
4. atrial fibrillation (AF)/ atrial flutter (AFL) 
5. atrial tachycardia (AT) 
6. atrioventricular nodal reentrant tachycardia (AVNRT)
7. monomorphic ventricular tachycardia (VT) 
8. brugada syndrome

Drug-Induced Bradyarrhythmias

一、分類：

• Sinus Node Dysfunction: This includes sinus bradycardia (heart rate <60 bpm), sinus pauses, and sinus arrest.
• Atrioventricular (AV) Block: This occurs when impulse conduction through the AV node and the His-Purkinje system is inhibited, or when refractoriness is prolonged.

二、機轉：

Sinus Node Dysfunction:

• Inhibition of Automaticity: The normal pacemaking function of the sinus node is reduced, leading to slower heart rates or pauses. (竇房結的正常跳動功能減弱，導致心跳減慢或出現停頓)
• Slowing of Conduction: Delayed conduction through the sinus node. (竇房結的傳導延遲)
• Prolongation of Repolarization (再極化延長): Longer repolarization times in the sinus node, which can contribute to bradycardia. (竇房結的再極化時間變長，這可能導致心跳變慢)

Atrioventricular Block: Occurs when impulse conduction through the AV node or His-Purkinje system is slowed or blocked.

三、Pharmacological Classes Associated with Bradyarrhythmias:

• Sympathetic Nervous System Inhibitors: 交感神經抑制劑
• β-blockers: These reduce sympathetic activity, decreasing sinus node automaticity.
• Clonidine: Stimulates central α-receptors, reducing norepinephrine release.

• Parasympathetic Nervous System Stimulants: 副交感神經促進劑
• Neostigmine, Pyridostigmine: These increase parasympathetic activity, suppressing sinus node function.
• Sodium &Calcium Channel Inhibitors: The action potentials in the sinus and AV nodes depend on these currents, and inhibiting them may lead to bradyarrhythmias.
• Specific Drug Mechanisms:
• Ivabradine: Inhibits hyperpolarization-activated cyclic nucleotide-gated (If) channels in the sinus node, slowing the heart rate.
• Fingolimod: Modulates sphingosine 1-phosphate receptors, which are involved in regulating heart rate and cardiac conduction.

四、Management of Drug-Induced Bradyarrhythmias

Avoidance and Minimization:

• Drugs that inhibit sinus or atrioventricular (AV) node function should not be used in patients with preexisting dysfunction unless a functioning pacemaker is present.
• Combinations of sinus or AV node inhibitors should be minimized, and maximum doses should not be exceeded.
• Liver and kidney disease can increase plasma concentrations of these drugs due to impaired metabolism and elimination, requiring dose adjustments.

Patient Education and Monitoring:

• Patients should be educated to recognize and report symptoms of bradycardia (e.g., dizziness, fatigue, syncope).
• Periodic 12-lead ECGs are recommended to monitor patients on sinus or AV node-inhibiting drugs, especially to check for progression of AV block.
• First-degree AV block is not a contraindication for these medications, but PR interval should be monitored to prevent progression.

Initial Management:

• Dose reduction or discontinuation of the offending agent should be the first step unless the drug is essential and alternatives are unavailable.
• In approximately 50% of patients, bradycardia may persist or recur, even after discontinuation, potentially requiring pacemaker implantation.

Precautionary Management:

• Electrolyte abnormalities, infection, and hypothyroidism should be corrected, as they can exacerbate bradyarrhythmias.
• For short-term management, atropine (0.5 mg IV every 3 to 5 minutes, up to 3 mg) can be administered unless the patient has undergone heart transplantation (due to risk of paradoxical heart block or sinus arrest).
• In hemodynamically compromised patients without coronary ischemia, isoproterenol, dopamine, dobutamine, or epinephrine may be used.
• In refractory cases, temporary pacing (transcutaneous or transvenous) may be necessary.

Overdose Management:

• Gastric lavage or activated charcoal may be useful in cases of recent overdose of sinus or AV node-blocking agents.
• Glucagon (3-10 mg IV bolus, followed by 3-5 mg/h infusion) can be administered for symptomatic or unstable bradycardia due to β-blocker or calcium channel blocker overdose.
• High-dose insulin therapy (1 unit/kg IV bolus, followed by 0.5 units/kg/h infusion) can improve heart rate and hemodynamics, especially in refractory bradyarrhythmias due to AV node-inhibiting drugs, with intravenous dextrose coadministered.
• Calcium chloride or calcium gluconate can be used in cases of calcium channel blocker overdose, though evidence on its hemodynamic benefits is variable, the risk is low.

Drug-Induced Supraventricular Arrhythmias (Atrial Fibrillation and Atrial Flutter)

一、Characteristics:

• Atrial Fibrillation (AF)
• Defined by rapid irregular atrial activity*.
• Absence of distinct P waves.
• Ventricular conduction can be rapid.

• Atrial Flutter (AFL)
• Defined by rapid regular atrial activity.
• Organized sawtooth pattern of atrial activation.

二、Drugs That May Cause or Exacerbate AF/AFL:

• Cardiovascular medications.
• Alcohol.
• Stimulants
• Anticancer agents
• Immunomodulators

三、Mechanisms of Drug-Induced AF/AFL

Stimulants: 

• Act via catecholaminergic augmentation.
• Result in β-receptor stimulation, shortened atrial effective refractory period, increased cAMP, increased cytosolic calcium, increased atrial automaticity, and pulmonary vein ectopic depolarizations.

Adenosine:

• Shortens atrial effective refractory period.
• Promotes pulmonary vein ectopy.

 Alcohol:

• Promotes sympathetic nervous system stimulation.
• Shortens atrial effective refractory period.
• Increases interatrial electromechanical delays.
• Acts via vagal pathways.

Bisphosphonates:

• Mechanism unclear but thought to involve release of inflammatory cytokines.
• Shortens atrial action potential duration and effective refractory period.

Flecainide and Propafenone (Sodium Channel Blockers):

• Slow atrial conduction.
• Increase the flutter cycle length.
• May cause 1:1 AV conduction with wide QRS.
• Atrioventricular node-blocking drugs should be co-prescribed in AFL patients using these drugs.

Amiodarone:

• Can induce AF via thyrotoxicosis in some patients.

Trastuzumab (herceptin) & etaracizumab

• Increases inflammation, oxidative stress, and reactive oxygen species.
• Causes ion channel dysfunction and remodeling, leading to AF.
• Mechanisms of drug-induced AF involve increased inflammation, oxidative stress, and ion channel dysfunction, leading to atrial remodeling.

Fluoxetine

Ondansetron

Ticagrelor

四、Risk Factors for Drug-Induced Atrial Fibrillation (AF) and Atrial Flutter (AFL)

• Adenosine: Increased risk in patients with premature atrial complexes.
• Alcohol: Risk increases with doses >30 g/day or ≥1–3 drinks/day; withdrawal syndrome can also trigger AF/AFL.
• Dobutamine: Risk factors include advanced age, prior AF, and heart failure.

Prevention Strategies

• Administer the lowest effective dose of drugs known to induce AF/AFL.
• Minimize or avoid the use of stimulants that increase the risk of AF/AFL.
• Limit alcohol intake to less than 30 g/day (roughly <7–14 drinks per week), or even complete abstinence, to reduce the risk of alcohol-related AF.
• Patients on AF/AFL-inducing drugs should:
  • Be aware of symptoms.
  • Monitor their pulse, heart rate, or rhythm daily, using a wearable monitor if at high risk.
  • Seek medical attention if experiencing persistent tachycardia, especially with symptoms.

五、Management of Drug-Induced AF/AFL

• Discontinuation of the offending drug is the first step in managing drug-induced AF/AFL.

Many hemodynamically stable patients convert back to sinus rhythm spontaneously.

• Rate Control:

Achieved with atrioventricular node-blocking agents like:

• β-blockers
• Calcium channel blockers (CCBs)
• Digoxin
• Duration of AF/AFL >48 hours or unknown:

• Transesophageal echocardiography should be performed to check for atrial thrombus before cardioversion.
• Alternatively, ≥3 weeks of therapeutic anticoagulation is required before cardioversion if thrombus status is unknown.
• Hemodynamically unstable patients:

May require urgent cardioversion following current clinical guidelines.

• Long-Term Management:

Can include anticoagulation, other pharmacological therapies, or catheter ablation, depending on the patient's condition and clinical guidelines.

• Drug Overdose (e.g., Theophylline):

Activated charcoal can be considered in cases of oral drug overdose causing AF.

Atrial Tachycardia (AT)

一、Characteristics.

• Atrial Tachycardia (AT) is defined by discrete P waves with heart rates of 100 to 250 bpm. (出現明確的P波)
• Focal AT (局部心房心搏過速): Arises from a single atrial site, characterized by uniform P-wave morphology. (來自單一的心房部位，特徵是P波形態一致)
• Multifocal AT (多源性心房心搏過速): Arises from multiple atrial sites, characterized by ≥3 different P-wave morphologies. (來自多個心房部位，特徵是出現≥3種不同的P波形態)
• 常見的異結點(extranodal sites)起源部位包括crista terminalis（終脊）、paranodal（旁結點）、paraseptal（旁間隔）、periannular（環周）、free wall（自由壁）、appendage（心耳）、pulmonary vein（肺靜脈）、coronary cusp（冠狀瓣）、coronary sinus（冠狀竇）等區域。.

二、機轉

• Increased automaticity: The ability of atrial cells to depolarize more frequently.
• Triggered activity: Abnormal calcium handling leading to ectopic beats.
• Microreentry: Small, rapid electrical loops that generate tachycardia.
• Multifocal AT is more common in patients with underlying pulmonary or structural heart disease, theophylline use, or hypomagnesemia.

三、Drugs That Can Cause AT:

• Catecholaminergic stimulants: β-agonists and phosphodiesterase inhibitors can trigger AT through increased catecholamine activity.
• Theophylline: Serum concentrations >20 μg/mL are associated with a higher risk of AT, including multifocal AT.

四、Digoxin Toxicity and AT:

• Digoxin-induced AT can occur, often with atrioventricular block.
• Mechanisms include:

1. Inhibition of Na+-K+-ATPase: Leads to increased intracellular Na+, Na+-Ca+ exchange, intracellular calcium overload, and enhanced atrial automaticity.
2. Vagomimetic or sympatholytic activity (擬迷走神經或交感神經抑制的): Results in atrioventricular block.

• Risk factors for digoxin-induced AT:

1. Serum digoxin concentrations >2 ng/mL.
2. Kidney disease, as digoxin is primarily eliminated through the kidneys.
3. 低血鎂(Hypomagnesemia).
4. Drug interactions (e.g., amiodarone, verapamil, quinidine) that can lead to elevated digoxin levels.

五、Strategies for Prevention or Risk Reduction of Drug-Induced Atrial Tachycardia (AT)

1. Avoidance of excessive stimulant use:Minimize or eliminate the use of stimulants that can trigger AT, such as caffeine, β-agonists, or other catecholaminergic agents.
2. Monitoring of serum digoxin concentrations:Regular monitoring, especially in patients with chronic or worsening kidney disease or those on interacting medications (e.g., amiodarone, verapamil, quinidine), as these factors can increase serum digoxin levels and the risk of toxicity.
3. Avoidance of high theophylline levels:Ensure that serum theophylline concentrations remain <20 μg/mL to reduce the risk of AT, particularly multifocal AT.

六、Treatment of Drug-Induced Atrial Tachycardia (AT)

• Focal AT:

1. Rate-controlling medications and antiarrhythmic drugs (e.g., flecainide, propafenone, sotalol, amiodarone, ibutilide) are used to control heart rate and suppress arrhythmia.
2. Overdrive pacing, catheter ablation, or synchronized direct current cardioversion may be used in patients with hemodynamic instability.
3. Cardioversion may be less effective if the arrhythmia is caused by enhanced automaticity, which is not easily terminated by this approach.
4. Some ATs may respond to adenosine for termination or suppression.

• Multifocal AT:

1. Treatment should include addressing underlying conditions (e.g., pulmonary disease, electrolyte imbalances).
2. Magnesium supplementation may be helpful, particularly in patients with hypomagnesemia.

• Digoxin Toxicity: Management of digoxin-induced AT may involve the use of digoxin immune antibody fragments (Digibind) to neutralize the toxic effects of digoxin.

Atrioventricular Nodal Reentrant Tachycardia (AVNRT)

一、Characteristics

• AVNRT is the most common type of traditional paroxysmal supraventricular tachycardia (PSVT).
• It is characterized by a regular, narrow QRS tachycardia, often with no visible P waves or with a P wave that merges with the QRS complex, creating a pseudo-R' (R prime) in lead V1.

二、盛行率

• Supraventricular tachycardia affects 2.29 per 1000 individuals.
• AVNRT accounts for approximately 60% of all supraventricular tachycardia cases.

三、Drug-Induced AVNRT:

• The proportion of AVNRT cases that are drug-induced is unknown.
• Some drugs reported to trigger AVNRT include theophylline (which is less commonly used today) and caffeine (which remains widely used).
• An ECG of supraventricular tachycardia associated with fluoxetine has been documented.

四、機轉

Reentrant Circuit:

• AVNRT occurs due to a reentrant circuit within the atrioventricular (AV) node.
• The circuit involves dual AV nodal pathways:
• Anterograde conduction occurs via the slow AV nodal pathway.
• Retrograde conduction occurs via the fast pathway.

Drug-Induced Mechanisms:

• Sympathetic Tone and Adrenergic Stimulation: In susceptible individuals, drugs that enhance AV nodal conduction can trigger AVNRT by increasing conduction velocity. (交感神經張力與腎上腺素能刺激：在敏感個體中，增強房室結傳導的藥物可能會藉由增加傳導速度來誘發AVNRT。)
• Premature Extrastimuli: Certain drugs may cause premature extrastimuli, which dissociate the refractory periods of the fast and slow pathways. This typically inhibits the fast pathway, allowing slow pathway conduction and triggering reentry. (過早刺激：某些藥物可能會導致過早刺激，進而使快速與緩慢傳導路徑的不反應期不同步。這通常會抑制快速路徑，使得慢速路徑的傳導得以進行，從而引發折返現象。) (指的是兩條傳導路徑恢復可激發動作電位的時間不同，而影響傳導的順序和心律的穩定性。)

Both mechanisms—enhanced AV nodal conduction and drug-induced premature extrastimuli—are often involved in drug-induced AVNRT.

五、Management of Drug-Induced AVNRT

• Discontinuation of the Offending Agent:

1. If AVNRT is drug-induced, the first step is to discontinue the triggering drug.
2. If discontinuation is not feasible, dose and frequency reduction and monitoring serum drug concentrations (if applicable) are recommended.

• Immediate Treatment:

1. Vagal maneuvers and intravenous adenosine are the first-line treatments for immediate management.
2. If these are ineffective, intravenous diltiazem, verapamil, or β-blockers can be used as alternatives.

• Long-Term Management: Catheter ablation of the slow AV nodal pathway offers a high long-term success rate with a low risk of complications for recurrent or drug-resistant AVNRT.

Drug-Induced Monomorphic Ventricular Tachycardia (VT)

一、Characteristics

• Monomorphic VT is a wide QRS complex (≥120 milliseconds) rhythm with a rate of ≥100 bpm, typically regular in nature.
• It has a uniform and stable QRS morphology.
• Sustained VT lasts ≥30 seconds or causes hemodynamic collapse.
• Common in patients with underlying structural heart disease such as:

• Coronary artery disease
• Cardiomyopathy (infiltrative, dilated, hypertrophic)
• Sarcoidosis
• Congenital heart disease
• Arrhythmogenic right ventricular cardiomyopathy
• Left ventricular noncompaction

二、Symptoms and Risks:

• Symptoms range from mild palpitations to sudden cardiac arrest, depending on the hemodynamic response.
• VT is considered an unstable rhythm, carrying a high risk of progressing to ventricular fibrillation and hemodynamic collapse.

三、Mechanisms of Drug-Induced Monomorphic VT:

• Sodium Channel Inhibition:
• Reduces ventricular conduction velocity and refractoriness, promoting reentry circuits.
• This mechanism is more critical in the presence of fibrosis or scar tissue (e.g., from a prior myocardial infarction or cardiomyopathy).
• Class IC antiarrhythmic agents (e.g., flecainide, propafenone) can increase the incidence of mortality due to VT in patients with these conditions.
• Sodium Channel Activation: Delays ventricular repolarization and increases ventricular automaticity.

• Intracellular Calcium Overload:
• Seen in patients with digoxin toxicity (Na+-K+-ATPase inhibition) or theophylline toxicity (phosphodiesterase inhibition).
• Results in afterdepolarizations and ventricular ectopy (triggered activity), leading to VT.
• Coronary Ischemia: Adenosine and dipyridamole can induce myocardial ischemia via a coronary steal phenomenon.
• Stimulation of Myocardial β2-Receptors: Drugs like dobutamine and epinephrine can stimulate β2-receptors, resulting in ventricular ectopic activity.
• Other Mechanisms: Drug-induced coronary vasospasm, myocarditis, or cardiomyopathy may also precipitate monomorphic VT.

四、Prevention of Drug-Induced Ventricular Tachycardia (VT)

• Avoidance of Offending Agents: Identify and avoid drugs that can induce VT, especially in high-risk patients.
• Careful Patient Selection: Class IC antiarrhythmic agents (e.g., flecainide, propafenone) should not be used in patients with prior myocardial infarction or cardiomyopathy, as these agents can increase mortality due to VT.
• Dose Adjustment and Monitoring:
• Therapeutic drug monitoring is crucial for medications with a narrow therapeutic window (e.g., digoxin, theophylline).
• For patients with impaired kidney function, hypomagnesemia, or hypokalemia, extra caution should be taken.
• Maintain serum digoxin concentrations below 2 ng/mL.
• Maintain serum theophylline concentrations below 20 μg/mL.

五、Treatment of Drug-Induced Monomorphic VT

• Hemodynamically Unstable Patients: Urgent synchronized cardioversion should be performed.
• Hemodynamically Stable Patients:

1. First-line treatment includes IV amiodarone, lidocaine, or procainamide.
2. Synchronized cardioversion can be performed if necessary, following appropriate sedation.

• Specific Treatments:

1. For flecainide-induced incessant VT, both intravenous lidocaine and amiodarone have been used successfully.
2. In cases of VT induced by bupivacaine or other local anesthetics, lipid emulsion therapy can be effective.

Brugada Syndrome

一、概論

• An inherited autosomal dominant channelopathy affecting the heart's electrical system, characterized by specific electrocardiographic (ECG) changes and a risk for ventricular arrhythmias.
• Only the type 1 ECG pattern is diagnostic for Brugada syndrome.

二、藥物引起的Brugada Syndrome

Defined by a normal pretreatment ECG that develops a Brugada pattern after exposure to certain drugs, although patients may already carry the genetic substrate for the condition.

三、Genetic Mutations:

• The most common genetic mutation is in the SCN5A gene, causing a loss of function in myocyte sodium channels.
• Other mutations include SCN10A, CACNA1C, CACNB2B, and KCNJ8 genes, which affect various ion channels involved in the heart’s electrical signaling.

四、Mechanism of Drug-Induced Brugada Syndrome:

• Drugs that unmask Brugada syndrome typically affect ventricular sodium currents (most common), and sometimes potassium or calcium currents.
• A detailed list of drugs to avoid in patients with Brugada syndrome is available online.

五、Clinical Presentation:

Some patients with drug-induced Brugada syndrome may also exhibit a spontaneous Brugada pattern during continuous ambulatory rhythm monitoring, even without drug exposure.

六、Treatment

• Discontinuation of the offending drug is the primary treatment.
• Ambulatory monitoring should be performed to rule out latent Brugada syndrome.
• VT associated with Brugada syndrome should be treated with cardioversion, defibrillation, or amiodarone.
• Procainamide should be avoided as it worsens sodium channel inhibition and can precipitate ventricular arrhythmias.
• Asymptomatic patients should be observed and avoid Brugada-provoking drugs.
• Electrophysiological testing for risk stratification is unclear, but an implantable cardioverter-defibrillator (ICD) may be necessary for patients with prior cardiac arrest, sustained VT, or a history of syncope with a spontaneous type I ECG.
• Subcutaneous ICD candidates should undergo drug challenge screening to rule out inappropriate shocks.
• Epicardial catheter ablation of the RVOT and quinidine are potential treatment options for selected patients.

Torsades de Pointes (TdP)

一、Characteristics:

• TdP is a polymorphic ventricular tachycardia associated with QT prolongation.
• It may be inherited (as part of congenital long-QT syndrome) or acquired, with the most common cause being medications.

二、Medications and TdP:

• Several drugs, such as terfenadine, astemizole, grepafloxacin, cisapride, and levomethadyl, have been withdrawn from markets due to TdP-associated deaths.
• However, >200 drugs remain available with the potential to induce TdP.

三、藥物誘發的TdP風險：

• QT延長藥物可能或有條件的誘發TdP的風險。
• TdP在一般人群中的發病率尚不清楚，但報導範圍從每百萬人年中男性2.5至4.0之間，女性略高，至每10萬人年約4例。
• 在成人重症加護病房中的TdP發病率約為0.07%，其中6%的心搏停止與TdP有關。

四、TdP的機轉

藥物主要通過抑制延遲整流鉀電流（IKr）來誘發TdP，這會延長動作電位持續時間，增加早期後去極化的風險，從而引發TdP。

某些藥物（如dofetilde、ibutilide、d-sotalol、thioridazine和紅黴素）透過增強後期鈉電流（INa-L），部分延長了心室動作電位持續時間。

五、TdP風險因素

TdP的風險在有QTc >500毫秒或QTc比治療前延長≥60毫秒的病人中更高，其他風險因素包括女性、年齡超過65歲、心動過緩、急性心肌梗塞、低鉀血症、低鎂血症、低鈣血症、心衰竭以及合併使用多種QT延長藥物。

六、預防藥物誘發的TdP：

• 糾正可修改的風險因素，如保持血鉀和血鎂濃度分別高於4.0 mEq/L和2.0 mg/dL。
• 避免合併使用抑制QT延長藥物代謝的藥物，並在腎臟或肝臟功能不全的病人中做適當的劑量調整。
• 對服用已知會引發TdP藥物的病人，尤其是有風險的人，應進行QTc間期監測，盡量將QTc保持在<500毫秒。

七、藥物誘發TdP的處理

• 停用引起QT延長的藥物，校正低鉀血症、低鎂血症和低鈣血症。
• 血液動力學不穩定的人應進行去顫治療，而穩定的TdP病人可以用靜脈注射Mg。
• 對於反復出現TdP且bradycardia的病人，可以使用overdrive pacing或isoproterenol 來增加心率並縮短QT間期。
• 沒有long-QT syndrome的人，口服mexiletine（200-450 mg QD）可以預防停用QT延長藥物、靜脈注射鎂及校正電解質異常後仍然反復出現的Torsades de Pointes (TdP)。
• 預防性給予高劑量硫酸鎂（magnesium sulfate）（5 g over 1 hour）可用來減少與ibutilide相關的TdP風險。

QT Interval Shortening

• Short-QT syndrome是一種罕見的先天性離子通道疾病，與增加的猝死（SCD）風險相關。文獻中尚未報告與Short-QT syndrome相關的藥物會引發心室性心律不整（ventricular proarrhythmia）或SCD的病例，且目前也沒有發佈避免在這類人群中使用縮短QT interval藥物的建議。然而，除非絕對必要，對於患有Short-QT syndrome的人，謹慎避免使用縮短QT interval的藥物可能是明智的。
• 可能縮短QT interval的藥物包括抗癲癇藥物（primidone, lamotrigine, phenytoin, rufinamide）、洋地黃苷類（digitalis glycosides）、IB類抗心律不整藥物（class IB antiarrhythmic drugs，如lidocaine, mexiletine），以及鉀離子整流劑（potassium rectifier agents，如pinacidil, levcromakalim, nicorandil）。

總結

Drug-induced arrhythmia is a significant concern, as various medications can disrupt the heart's electrical system, leading to abnormal heart rhythms.

QT Prolongation and Torsades de Pointes (TdP)

Several drug classes are known to prolong the QT interval on an electrocardiogram (ECG), increasing the risk of a life-threatening arrhythmia called Torsades de Pointes (TdP). The QT interval reflects the time it takes for the ventricles to repolarize after each heartbeat. Prolongation of this interval creates an electrical instability that can lead to TdP, a polymorphic ventricular tachycardia that can degenerate into ventricular fibrillation.

Examples of medications that can prolong the QT interval and increase the risk of TdP include:

• Antiarrhythmics: Class Ia (e.g., procainamide, disopyramide), Class III (e.g., amiodarone, sotalol, dofetilide)
• Antipsychotics: Phenothiazines, haloperidol, atypicals
• Antimicrobials: Macrolides, quinolones, azoles
• Other: Antiemetics (droperidol, 5-HT3 antagonists), alfuzosin, methadone, ranolazine, lithium, tricyclic antidepressants

Nonantiarrhythmic drugs can also contribute to QT prolongation and TdP. These include arsenic trioxide, macrolide antibiotics, fluoroquinolones, azole antifungals, methadone, antidepressants, organophosphorus compounds, and antipsychotics.

It's important to note that the risk of TdP is often associated with:

• Drug Interactions: Certain drugs can inhibit the metabolism of other drugs, leading to higher-than-desired plasma levels and an increased risk of QT prolongation.
• Impaired Kidney or Liver Function: Impaired elimination of drugs can also contribute to elevated drug levels and QT prolongation.
• High Doses: Taking higher than recommended doses of medications can increase the risk of QT prolongation.

Other Drug-Induced Arrhythmias

Besides QT prolongation and TdP, drugs can induce other types of arrhythmias:

• Bradyarrhythmias:
  • Beta-blockers, calcium channel blockers, amiodarone, lithium, and digoxin can cause bradycardia and AV block.
  • Loperamide, an opioid antidiarrheal, can block sodium and potassium channels in cardiac tissue, leading to QT prolongation, QRS widening, and potentially life-threatening bradyarrhythmias.
• Tachyarrhythmias:
  • Dopamine, while a chronotropic β-agonist used in treating bradycardia, can also lead to tachycardia and arrhythmias.
  • Epinephrine can similarly cause arrhythmias.
  • Verapamil, a calcium channel blocker, can paradoxically cause a rapid ventricular response in patients with atrial fibrillation (AF) in the presence of accessory pathways.

Management of Drug-Induced Arrhythmias

Management of drug-induced arrhythmias involves:

• Identifying and Discontinuing the Offending Drug: This is often the first step in managing drug-induced arrhythmias.
• Correcting Electrolyte Imbalances: Electrolyte disturbances like hypokalemia and hypomagnesemia can exacerbate arrhythmias and should be corrected.
• Treating the Underlying Cause: Addressing underlying conditions contributing to arrhythmias, such as ischemia or heart failure, is crucial.
• Using Antiarrhythmic Medications: In some cases, antiarrhythmic drugs may be necessary to control the arrhythmia. However, it's essential to select agents that do not further prolong the QT interval or contribute to proarrhythmic effects.
• Magnesium Sulfate: Magnesium sulfate is frequently used to treat TdP due to its ability to block calcium channels and potentially stabilize the membrane gradient.

Prevention of Drug-Induced Arrhythmias

Prevention of drug-induced arrhythmias involves:

• Careful Medication Selection: Consider the potential for QT prolongation and arrhythmias when selecting medications, especially in patients with risk factors.
• Monitoring: Monitor patients on medications known to prolong the QT interval with ECGs.
• Electrolyte Monitoring: Regularly monitor electrolytes, particularly potassium and magnesium.
• Patient Education: Educate patients about the potential side effects of their medications and when to seek medical attention.

Overall, careful consideration of medication choices and close monitoring are crucial for preventing and managing drug-induced arrhythmias.

延伸閱讀：

Drug-Induced Arrhythmias A Scientific Statement From the American Heart Association (link)