Class II: Beta blockers

• Treat both supraventricular and ventricular arrhythmias.
• Slow channel blockers, so they work at the sinoatrial and atrioventricular nodes; more generally, as we’ve learned elsewhere, beta blockers reduce sympathetic stimulation.
• We draw the normal curve of an action potential through the nodes.
• Then, we show that beta blockers inhibit phase 4 depolarization and slow conduction through the atrioventricular node.
• Suppress ectopic pacemakers.
• Slow heart rate and reduce contractility.
• Prolong the PR interval on ECG.
• Examples
  – Drugs that are often used to prevent recurrent myocardial infarction:
  Propranolol, which also stabilizes membranes (a class I action)
  Metoprolol
  Nadolol
  Timolol
  – Esmolol is a cardioselective beta-1 receptor blocker and is short-acting.
  – Thus, it is used to treat acute arrhythmias.
• Common beta blocker side effects: bradycardia, hypotension, bronchospasm (with non-selective beta blockers, specifically), and, myocardial depression.

Class III: Potassium Channel Blockers

• Treat tachyarrhythmias, including re-entry arrhythmias.
• We Draw the normal curve of an action potential in the ventricles.
• Then, we indicate that potassium channel blockers delay repolarization, prolong the action potential, and lengthen the effective refractory period.
• The drugs we’ll focus on the most, amiodarone and its derivative, slow the heart rate and atrioventricular node conduction; these additional actions are due to their abilities to block beta adrenoreceptors, sodium, potassium, and calcium channels.
• Class III drugs prolong the QT interval on the ECG.
• Examples
  – Amiodarone, which, due to the various channels and receptors it blocks, is a mix of classes I-IV. Its wide spectrum of action makes it a popular drug of choice in a variety of arrhythmias.
  Amiodarone is lipophilic, and is widely distributed through the body tissues.
  Widespread potential side effects:
  Liver toxicity and cirrhosis
  Interstitial pneumonitis, which can lead to pulmonary fibrosis
  Corneal microdeposits, which are caused by amiodarone-induced lipidosis in the eye
  (we show their “whorl-like” pattern(
  Photosensitivity/phototoxicity can produce a rash or even give the skin a gray-blue tint
  And, because amiodarone is iodine-rich, it can cause hypo- or hyperthyroidism.
  Amiodarone can also cause sinus bradycardia
  – Dronedarone is a synthetic, non-iondinated derivative of amiodarone (it doesn’t have iodine).
  It is used to treat atrial fibrillation, and is generally considered less toxic, but less powerful, than amiodarone.
  It is, however, associated with liver toxicity.
  – Sotalol, which also has class I beta blocking actions, is associated with torsades de pointes.
• As a warning, write that most class III drugs are significantly pro-arrhythmic; amiodarone and dronedarone are important exceptions, as they less likely to precipitate arrhythmias.

Class IV: Calcium Channel Blockers

• Treat supraventricular arrhythmias and to reduce ventricular rate in atrial flutter and atrial fibrillation.
• They block calcium channels, so they are most effective at the sinoatrial and atrioventricular nodes, which rely on calcium ions for rate control.
• We draw the curve of a normal nodal action potential, and show that calcium channel blockers prolong nodal conduction and the effective refractory period.
• They prolong the PR interval on ECG (like the Class II drugs).
• We use non-dihydropyridine calcium channel blockers
• Examples
  – Verapamil and Diltiazem; both target myocardial cells, and diltiazem has some vasodilator effects.
  Both drugs are associated with constipation, and, due to their negative inotropic effects, can cause bradycardia and lower cardiac output.
  Thus, use caution when combining these drugs with beta blockers, which have similar effects, and, avoid using in patients with heart failure with reduced ejection fraction.

Class V: Others

Finally, let’s consider the “others” category, sometimes collectively called “Class V”.

Adenosine is used to treat supraventricular tachycardias; it slows or blocks conduction in the atrioventricular node.
– It’s important to know that theophylline (a common asthma medication) and caffeine reduce adenosine’s efficacy by blocking its receptors.
– Adenosine may trigger bronchospasm.
Magnesium ions are sometimes used to treat torsades de pointes and digoxin toxicity.
Potassium ions may be used in some patients to slow conduction and can suppress ectopic pacemakers.
Digoxin can be used in some patients to treat atrial flutter or atrial fibrillation; it slows or blocks conduction in the atrioventricular node by inhibiting sodium-potassium ATPase.
– However, digoxin can cause ectopic arrhythmias, gastrointestinal and visual side effects, and breast enlargement (gynecomastia, in males), and has been associated with increased risk of breast and uterine cancer, likely due to its phyto-estrogen effects.