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Questions and Answers
What is a notable side effect that may occur with amiodarone treatment?
What is a notable side effect that may occur with amiodarone treatment?
In which situation should dronedarone be avoided due to increased risk?
In which situation should dronedarone be avoided due to increased risk?
What is the recommended initial approach to starting dofetilide?
What is the recommended initial approach to starting dofetilide?
Which class II antiarrhythmic drug is known as a selective β1-adrenergic blocker?
Which class II antiarrhythmic drug is known as a selective β1-adrenergic blocker?
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Which of the following agents is classified solely as a Class III antiarrhythmic?
Which of the following agents is classified solely as a Class III antiarrhythmic?
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What is the route of administration for sotalol?
What is the route of administration for sotalol?
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Which mechanism is associated with class III antiarrhythmic drugs?
Which mechanism is associated with class III antiarrhythmic drugs?
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What important monitoring is necessary for a patient receiving ibutilide?
What important monitoring is necessary for a patient receiving ibutilide?
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What is a contraindication for the use of sotalol?
What is a contraindication for the use of sotalol?
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What is a notable characteristic of amiodarone?
What is a notable characteristic of amiodarone?
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Which medication requires the patient to avoid grapefruit juice?
Which medication requires the patient to avoid grapefruit juice?
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Which class of drugs does sotalol belong to?
Which class of drugs does sotalol belong to?
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What adverse effect is associated with amiodarone due to its structural similarity to thyroid hormones?
What adverse effect is associated with amiodarone due to its structural similarity to thyroid hormones?
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What is the primary FDA indication for amiodarone?
What is the primary FDA indication for amiodarone?
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Which antiarrhythmic agent does NOT require dietary considerations for its absorption?
Which antiarrhythmic agent does NOT require dietary considerations for its absorption?
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How is esmolol metabolized in the body?
How is esmolol metabolized in the body?
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What is a serious side effect associated with the use of dronedarone?
What is a serious side effect associated with the use of dronedarone?
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What is a common feature of class III antiarrhythmic drugs?
What is a common feature of class III antiarrhythmic drugs?
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Which of the following is NOT a property of propranolol?
Which of the following is NOT a property of propranolol?
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What can improve the variable oral bioavailability of amiodarone and dronedarone?
What can improve the variable oral bioavailability of amiodarone and dronedarone?
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What is the primary reason for hospitalizing patients when initiating treatment with amiodarone?
What is the primary reason for hospitalizing patients when initiating treatment with amiodarone?
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Which of the following medications is contraindicated in patients with current or recent heart failure?
Which of the following medications is contraindicated in patients with current or recent heart failure?
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What effect does the structure of amiodarone have on thyroid function?
What effect does the structure of amiodarone have on thyroid function?
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Which class of drugs should Sotalol be compared with due to its dual activity?
Which class of drugs should Sotalol be compared with due to its dual activity?
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Which serious adverse effect is associated with dofetilide treatment?
Which serious adverse effect is associated with dofetilide treatment?
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What is the recommended method for administering dronedarone to enhance bioavailability?
What is the recommended method for administering dronedarone to enhance bioavailability?
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What is a common side effect experienced by patients taking amiodarone?
What is a common side effect experienced by patients taking amiodarone?
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What is a critical precaution that needs to be taken when administering ibutilide?
What is a critical precaution that needs to be taken when administering ibutilide?
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Which of the following drug interactions should be closely monitored in patients taking amiodarone?
Which of the following drug interactions should be closely monitored in patients taking amiodarone?
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What clinical condition is a contraindication for the use of Bretylium?
What clinical condition is a contraindication for the use of Bretylium?
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Which characteristic is unique to esmolol compared to other class II antiarrhythmic drugs?
Which characteristic is unique to esmolol compared to other class II antiarrhythmic drugs?
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What is the mechanism of action for class III antiarrhythmic drugs?
What is the mechanism of action for class III antiarrhythmic drugs?
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Which of the following statements about sotalol is true?
Which of the following statements about sotalol is true?
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How does amiodarone affect the action potential?
How does amiodarone affect the action potential?
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What is a significant adverse effect associated with amiodarone?
What is a significant adverse effect associated with amiodarone?
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Which drug class does dronedarone belong to?
Which drug class does dronedarone belong to?
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How are class II antiarrhythmic drugs primarily administered?
How are class II antiarrhythmic drugs primarily administered?
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Which is true about the metabolic pathway of propranolol?
Which is true about the metabolic pathway of propranolol?
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What is a notable feature of amiodarone regarding its solubility?
What is a notable feature of amiodarone regarding its solubility?
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What effect does blocking K+ channels have on the cardiac action potential?
What effect does blocking K+ channels have on the cardiac action potential?
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Study Notes
Class II Antiarrhythmic Drugs
- Class II antiarrhythmic drugs are β-adrenergic blockers
- Propranolol and sotalol are nonspecific β-adrenergic blockers
- Esmolol is a selective β1-adrenergic blocker
- β-blockers reduce sympathetic stimulation of cardiac tissue which decreases cAMP levels, calcium influx, and the force and rate of cardiac contraction
- Sotalol is considered a Class II agent due to its β-adrenergic blocking action
- Propranolol and esmolol are administered intravenously while sotalol is administered orally as a tablet or syrup
- Esmolol is rapidly hydrolyzed to an inactive carboxylate with a half-life of ~9 minutes
- Sotalol is nearly completely absorbed, not protein bound, and is excreted unchanged
- Propranolol experiences rapid first-pass metabolism, low bioavailability, and is highly bound to plasma protein
Class III Antiarrhythmic Drugs
- Class III antiarrhythmic drugs block K+ channels, leading to prolonged action potential duration
- Class III drugs primarily act during phase 3 of the action potential
- Prolonged action potential duration delays repolarization resulting in a prolonged refractory period
- Several class III drugs have overlapping mechanisms affecting other parts of the action potential
Amiodarone
- Amiodarone blocks Na+ channels, inhibits β-receptors, and has weak Ca2+ channel blocking activity
- Amiodarone is lipophilic, insoluble in water, and able to cross the blood-brain barrier
- Variable oral bioavailability of amiodarone can be improved by taking it with food
- Amiodarone has structural similarity to thyroid hormones, accounting for some of its adverse effects
- Amiodarone has significant adverse effects including pulmonary toxicity, hepatic dysfunction, neuromuscular symptoms, photosensitivity, hypo- or hyperthyroidism, QT prolongation, nausea, vomiting, constipation, weight loss, fatigue, heart block, and heart failure
- Amiodarone is available intravenously and orally
- Amiodarone has a long half-life of 13-103 days, has 50% bioavailability, and 96% protein binding
- Amiodarone is metabolized by hepatic enzymes 3A4 and 2C8
- Amiodarone's active metabolite is N-desethylamiodarone
Dronedarone
- Dronedarone is similar to amiodarone, additionally inhibiting α-adrenergic receptors
- Dronedarone is available orally
- Dronedarone has a half-life of 13-19 hours and 98% protein binding
- Dronedarone has 15% bioavailability when taken with food
- Dronedarone is metabolized by the hepatic enzyme 3A4
- Dronedarone has significant adverse effects including QT prolongation, heart failure, liver injury, and pulmonary toxicity
- Dronedarone is structurally related to amiodarone without iodine and fewer organ toxicities
- Dronedarone is associated with increased mortality in patients with symptomatic heart failure, class IV heart failure, or those who cannot be cardioverted
Ibutilide
- Ibutilide is considered a pure Class III agent
- Ibutilide produces an influx of Na+ in slow Na+ channels
- Ibutilide is available intravenously
- Ibutilide is metabolized by the liver
- Ibutilide is used for short-term conversion of atrial fibrillation
- Ibutilide has significant adverse effects including ventricular tachycardia and QT prolongation (torsades de pointes)
Dofetilide
- Dofetilide is considered a pure Class III agent
- Dofetilide is available orally
- Dofetilide is used for atrial fibrillation and flutter
- Dofetilide has significant adverse effects including torsades de pointes, heart block, and ventricular dysrhythmias
- Dofetilide is a REMS medication requiring an inpatient initiation
- Dofetilide requires dose adjustments based on creatinine clearance
Sotalol
- Sotalol is available intravenously and orally
- Sotalol has β-adrenergic blocking activity (Class II)
- Sotalol is used for supraventricular and ventricular dysrhythmias
- Sotalol has significant adverse effects including heart failure exacerbation, torsades de pointes, and QT prolongation
- Sotalol requires dose adjustments based on creatinine clearance
Bretylium
- Bretylium is available intravenously
- Bretylium is used for ventricular dysrhythmias
- Bretylium acts by transiently increasing NE release followed by blockade of NE release
- Bretylium has significant adverse effects including hyperthermia, arrhythmias, and bradycardia
- Bretylium requires dose adjustments based on creatinine clearance
Class II Antiarrhythmic Drugs
- Beta-adrenergic blockers that decrease sympathetic stimulation of cardiac tissue
- Reduce cAMP levels, decrease calcium influx, leading to decreased force and rate of cardiac contraction
- Propranolol and sotalol are nonspecific beta-blockers
- Esmolol is a selective beta1-adrenergic blocker
- Propranolol experiences rapid first-pass metabolism, low bioavailability, and is highly bound to plasma protein
- Sotalol is a class II agent due to its beta-adrenergic blocking properties
- Sotalol is nearly completely absorbed following oral administration, not protein bound, and is excreted unchanged
- Esmolol rapidly hydrolyzed to an inactive carboxylate with a half-life of ∼9 minutes
- Administered as water-soluble hydrochloride salts as an enantiomeric mixture
- Esmolol and propranolol are administered via intravenous infusion, while sotalol is administered orally as a tablet or syrup
Class III Antiarrhythmic Drugs
- Block potassium channels, leading to prolonged action potential by blocking outward potassium current
- Most of the class III drugs act through phase 3 of the action potential
- Prolonged action potential duration delays repolarization, leading to a prolonged refractory period
- Several class III drugs have overlapping mechanisms affecting other parts of the action potential
Amiodarone
- Sodium channel blocker, inhibits beta-receptors, and is a weak calcium channel blocker
- Lipophilic, insoluble in water, and able to cross the blood-brain barrier
- Variable oral bioavailability that can be improved by taking with food
- Has structural similarity to thyroid hormones, accounting for some of its adverse effects
- Associated with severe adverse effects, including:
- Pulmonary toxicity
- Hepatic dysfunction
- Neuromuscular symptoms
- Photosensitivity
- Hypo- or hyperthyroidism
- QT prolongation
- Nausea, vomiting, constipation, weight loss, fatigue, heart block, and heart failure
Dronedarone
- Similar to amiodarone, plus inhibits alpha-adrenergic receptors
- Structurally related to amiodarone without iodine, with fewer organ toxicities
- Associated with QT prolongation, heart failure, liver injury, and pulmonary toxicity
Ibutilide
- Produces an influx of sodium in slow sodium channels, which may be its major action
Sotalol
- Nonselective beta-blocker
Dofetilide
- Pure class III agent
Bretylium
- Not currently available
- MOA: Transient increase in norepinephrine release followed by a block in norepinephrine release
Considerations for Class III Antiarrhythmic Drugs
- Amiodarone (Cordarone, Pacerone®)
- Available as IV and PO
- Life-threatening ventricular arrhythmias
- Off-label:
- Atrial fibrillation, Supraventricular dysrhythmias, ACLS
- Class I, II, III, IV; also alpha-block
- Long half-life = 13-103 days
- Bioavailability: 50%
- Protein binding: 96%
- Hepatic metabolism via 3A4 and 2C8
- Active metabolite: N-desethylamiodarone
- Food impacts absorption, take consistently with or without food
- Black Box Warning: Only for life-threatening arrhythmias due to toxicity; pulmonary toxicity (hypersensitivity pneumonitis or interstitial/alveolar pneumonitis); liver toxicity; Exacerbate arrhythmia
- Contraindications: Cardiogenic shock; 2nd or 3rd degree heart block; bradycardia; Iodine allergy
- Precautions: Hyper/hypothyroidism; peripheral neuropathy; optic neuritis; corneal deposits
- Common adverse effects: Nausea; vomiting; thyroid dysfunction; bradycardia; hypotension (IV); photosensitivity; paresthesias; ataxia; increased LFTs; blue-gray skin discoloration
- Serious adverse effects: Ventricular arrhythmias; AV block and increased QTc (less than other agents); SJS/TENS; Visual impairment; Pulmonary fibrosis
- Drug Interactions: Many, including grapefruit juice; warfarin; digoxin; theophylline; simvastatin; caution with QT prolonging drugs
- Patients must be hospitalized for IV loading dose and maintenance dose initiated
- Dronedarone (Multaq®)
- Available as PO
- Atrial (A Fib, AF) dysrhythmias
- Class I, II, III, IV; also alpha-block
- Half-life: 13-19 hours
- Protein binding: 98%
- Bioavailability: 15% with food
- Hepatic metabolism via 3A4 – No dose adjustment required
- Black Box Warning: Symptomatic HF, Class IV HF or Pts who can’t be cardioverted due to increased mortality
- Contraindications: QTc > 500 msec; PR interval > 280 msec; 2nd or 3rd degree heart block; bradycardia; Severe decreased liver function
- Precautions: COPD/Asthma; hypotension; CHF
- Common adverse effects: Nausea; abdominal pain; diarrhea; increased serum creatinine (not directly nephrotoxic)
- Serious adverse effects: Heart failure; Increased QTc; Liver failure; Heart block
- Drug Interactions: QT prolonging drugs; 3A4 inhibitors or inducers; grapefruit juice
- Pregnancy Category: X
- Take with morning and evening meals
- Use two forms of birth control while taking this medication (females)
- Ibutilide (Covert®)
- Available as IV
- Atrial (A Fib, AF) dysrhythmias
- Pure Class III agent
- Hepatic metabolism
- No dosage adjustment required
- Black Box Warning: Continuous ECG monitoring; Risk of V-tach and increased QTc (torsades)
- Precautions: QTc > 440 msec; bradycardia; CHF; increased QT drugs; decreased magnesium; decreased potassium,
- Common adverse effects: Bradycardia
- Serious adverse effects: Heart block; Torsades de pointes
- Drug Interactions: QT prolonging drugs
- Short-term use only for conversion of dysrhythmia
- Dofetilide (Tikosyn®)
- Available as PO
- Atrial fibrillation/ flutter
- Off label: Supraventricular dysrhythmias
- Pure Class III agent
- Renal: Dose adjustment when creatinine clearance < 60 mL/min
- Black Box Warning: Monitoring for prolonged QT interval (QTc> 440 msec); QT drugs
- Contraindications: QTc> 440 msec; QT drugs
- Precautions: 3A4 drugs; decreased magnesium; decreased potassium
- Common adverse effects: Headache, dizziness, chest pain
- Serious adverse effects: Torsades; Heart block; Ventricular dysrhythmias
- Drug Interactions: Verapamil; megestrol, cimetidine; ketoconazole; fluconazole; QT prolonging drugs
- REMS medication guide required
- Inpatient initiation
- Sotalol (Betapace®)
- Available as IV and PO
- Supraventricular dysrhythmias, Ventricular dysrhythmias
- Also has class II activity
- Renal: Dose adjustment when creatinine clearance < 60 mL/min
- Black Box Warning: Initiate or re-initiate in hospital; CI if QTc > 450 msec
- Contraindications: Cardiogenic shock; 2nd or 3rd degree heart block; bradycardia
- Precautions: COPD/Asthma; hypotension; CHF; QT prolongation
- Common adverse effects: Bradycardia; Palpitations; Dizziness; Dyspnea; Fatigue
- Serious adverse effects: HF exacerbation; Torsades de pointes
- Drug Interactions: QT prolonging drugs; other drugs that cause increased heart rate
- Products differ with different renal dosing requirements and restrictions
- Avoid abrupt withdrawal
- Mask hypoglycemia symptoms
- Do not take within 2 hours of aluminum or magnesium containing antacids
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Description
This quiz covers essential information about Class II and III antiarrhythmic drugs, focusing on their mechanisms, administration, and pharmacokinetics. Topics include β-adrenergic blockers like Propranolol, Sotalol, and Esmolol, as well as the action of Class III drugs that block K+ channels. Test your understanding of these critical cardiovascular medications.
