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Drugs for Arrhythmias. A. Pathophysiology of arrhythmias. Arrhythmias are a group of conditions in which the muscle contraction of the heart is irregular, and they occur in both healthy and diseased hearts. .

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a pathophysiology of arrhythmias
A. Pathophysiology of arrhythmias
  • Arrhythmias are a group of conditions in which the muscle contraction of the heart is irregular, and they occur in both healthy and diseased hearts.
b arrhythmia therapy
B. Arrhythmia therapy
  • Antiarrhythmic drugs do not cure the underlying causes of an arrhythmia. Instead, they attempt to restore the normal cardiac rhythm.
1 class i antiarrhythmic drugs na 1 channel blockers
1. Class I antiarrhythmic drugs (Na1+ channel blockers)
  • This class of drugs reduces the excitability of the heart by slowing the spread of impulse conduction across the heart.
slide7
Sodium channel blockers are similar in structure and action to the local anesthetics.
  • This is the largest class of antiarrhythmic drugs.
slide9
Phase 4: The resting membrane potential, when the cell is not being stimulated (represented by baseline on the ECG).
slide10

Phase 0: This is the rapid depolarization phase and occurs with the opening of the Na1+ channels and the rapid influx of Na1+ into the cell.

slide11

Phase 1: This phase of the action potential occurs with the closure of the Na1+ channels. There is a transient net outward current due to the movement of K1+ and Cl1- ions. Phase 0 and 1 together correspond to the QRS complex of the ECG.

slide12

Phase 2: This is the plateau phase of the action potential and occurs because of the balanced inward movement of Ca2+ ions through calcium channels, and outward movement of K1+ ions through potassium channels. It corresponds to the ST segment of the ECG.

slide13

Phase 3: In this phase of the action potential, the K1+ channel is still open, allowing more K1+ to leave the cell, resulting in a net loss of positive charge, which causes the cell to repolarize. Phase 3 corresponds to the T wave of the ECG.

slide14

a. Class IAThey slow the rate of rise of phase 0 and lengthen the action potential and are indicated for managing a variety of atrial and ventricular arrhythmias.

quinidine gluconate 62 quinidine
quinidine gluconate (62% quinidine):
  • Quinidine is indicated for a wide variety of both atrial and ventricular arrhythmias. The off label use of this is the treatment of malaria.
slide17
Dosage:
  • IV: infuse at 16 mg/min until arrhythmia is resolved;
  • PO: 325 – 650 mg every 6 hours.
quinidine sulfate 83 quinidine
quinidine sulfate (83% quinidine):
  • Dosage: PO: 400 – 600 mg every 2 – 3 hours until arrhythmia is resolved, for supraventricular tachycardia;
slide21
It’s side effects include a syndrome called "cinchonism" consisting of various sound and visual disturbances (hallucinations, ringing in the ears), salivation, GI disturbances, weakness, fatigue, rashes, headache, and confusion.
slide22
It can cause/aggravate Torsades de pointes (an uncommon variant of ventricular tachycardia), as can all class IA drugs
procainamide procanbid promine pronestyl
procainamide (Procanbid, Promine, Pronestyl)
  • procainamide first approved for use in the United States in 1950, is indicated for a wide variety of both atrial and ventricular arrhythmias.
slide24
Dosage: IV: 100 mg every 5 minutes until arrhythmia is resolved, or 500 – 600 mg every 25 – 30 minutes followed by maintenance infusion of 2 – 6 mg/min.
slide25
It’s most serious adverse effects include seizures, asystole, heart block, ventricular arrhythmias and agranulocytosis.
slide26

It’s most common adverse effects are GI disturbances. Some individuals experience lupus-like symptoms (rash, muscle pain).

disopyramide norpace rythmodan
disopyramide (Norpace, Rythmodan)
  • disopyramide is usually only used after quinidine and procainamide have been ruled out as possibilities. It is indicated for the treatment of ventricular tachycardia.
slide28
Dosage: PO: 150 mg every 6 hours, not to exceed 800 mg/day
  • Disopyramide can aggravate or precipitate severe CHF.
slide29
Other adverse effects associated with disopyramide include dry mouth, blurred vision, urinary retention, and constipation.
slide30

b. Class IBThey shorten the action potential and are indicated for the treatment of ventricular tachycardia and prevention of ventricular fibrillation

lidocaine xylocaine
lidocaine (Xylocaine)
  • lidocaine is indicated for the treatment of ventricular arrhythmias.
  • Dosage: IV: 50 – 100 mg bolus over 2 minutes, then 1 – 4 mg/min infusion
slide33
It’s most serious adverse effects include cardiac arrest, anaphylaxis, and seizures. It’s most common adverse effects include agitation, confusion, slurred speech, tremors and drowsiness.
mexiletine mexitil
mexiletine (Mexitil)
  • mexiletine (Mexitil) is structurally similar to lidocaine, except it can be administered orally.
slide36
Dosage mexiletine:
  • PO: 400 mg loading dose, then 200 mg more in 8 hours, then 200 – 400 mg every 8 hours
slide37

c. Class ICThey have no effect on the length of the action potential, but reduce the rate of rise of phase 0. These drugs are indicated for the treatment of ventricular tachycardia and supraventricular tachycardia.

flecainide tambocor
flecainide (Tambocor)
  • flecainide (Tambocor) is used in the treatment of supraventricular tachycardia.
slide40
Dosage:
  • PO: 100 mg every 12 hours, increased by 50 mg bid until arrhythmia is resolved (maximum daily dose of 400 mg).
slide41
It’s most serious adverse effects are CHF and arrhythmias (V-tach).
  • It’s most common adverse effects are dizziness and blurred vision.
propafenone rythmol
propafenone (Rythmol)
  • propafenone(Rythmol) is used in the treatment of both ventricular tachycardia and supraventricular tachycardia
slide43
Dosage:
  • PO: 150 mg every 8 hours, may be increased up to 300 mg every 8 – 12 hours.
slide44
It’s most serious adverse effects are the events that it is indicated for, ventricular tachycardia and supraventricular tachycardia
slide45
It’s most common adverse effects include dizziness, altered taste, nausea, vomiting and constipation.
2 class ii antiarrhythmic drugs beta blockers
2. Class II antiarrhythmic drugs (beta blockers)
  • This class of drugs are the beta blockers which block the effects of catecholamines at the β receptors, thereby decreasing sympathetic activity and resulting in a decrease in the heart rate.
slide47
They are indicated for the treatment of atrial fibrillation and atrial flutter.
  • These class II drugs include acebutolol, esmolol, propanolol, and sotalol.
3 class iii antiarrhythmic drugs k 1 channel blockers
3. Class III antiarrhythmic drugs (K1+ channel blockers)
  • By blocking K1+ channels, these drugs lengthen the action potential (by lengthening the refractory period/resting stage).
slide49
This tends to decrease the frequency of arrhythmias. They are indicated for the treatment of atrial fibrillation, atrial flutter,
amiodarone cordarone pacerone
amiodarone (Cordarone, Pacerone)
  • amiodarone is indicated for the treatment of life threatening ventricular arrhythmias, but only when the patient is unresponsive to less toxic agents (i.e. dofetilide or ibutilide)
slide53
Dosage:
  • PO: 800 – 1600 mg/day in 1 – 2 doses for 1 – 3 weeks, then 600 – 800 mg/day in 1 – 2 doses for 1 month, then 400 mg/day for maintenance
slide54
IV: 150 mg over 10 minutes, then 360 mg over 6 hours, then 540 mg over 18 hours. Maintenance infusion of 0.5 mg/minute until PO therapy is initiated.
slide55
Amiodarone has a very large number of adverse effects, affecting almost every part of the body:
  • ARDS
  • pulmonary fibrosis
  • CHF
  • worsening of arrhythmias
slide56
inflammation of the liver
  • nausea
  • vomiting
  • constipation
  • dizziness
  • fatigue
slide57
thyroid dysfunction
  • photosensitivity
  • involuntary movement
  • tremors
  • bradycardia
slide58
hypotension
  • visual problems
  • discoloration of the skin
  • decreased libido
dofetilide tikosyn
dofetilide (Tikosyn)
  • dofetilide (Tikosyn) is indicated for the conversion of atrial fibrillation and atrial flutter to normal sinus rhythm
slide60
Dosage:
  • PO: Initial dose is 500 μg bid; maintenance dose is 250 μg bid
slide61
It’s most serious adverse effects are ventricular arrhythmias. It’s most common adverse effects are dizziness, headache and chest pain.
ibutilide corvert
ibutilide (Corvert)
  • ibutilideis indicated for the conversion of atrial fibrillation and atrial flutter to normal sinus rhythm, especially within 1 week of bypass surgery.
slide63
Dosage: 1 mg infusion, that may be repeated every 10 minute
  • Dosage after cardiac surgery: 0.5 mg infusion, may be repeated once.
slide64
It’s most serious adverse effects are ventricular arrhythmias. It’s most common adverse effects are headache and nausea.
4 class iv antiarrhythmic drugs
4. Class IV antiarrhythmic drugs
  • These drugs prevent the movement of calcium into myocardial cells which slows depolarization and decreases the heart rate.
slide66

In addition, these drugs decrease the force of myocardial contractions (they would not be recommended in patients with CHF).

slide67

ALL CCB’s produce vasodilation, however, only verapamil and diltiazem have direct actions on the heart.

slide68
These drugs are effective in treating a variety of arrhythmias including atrial flutter, atrial fibrillation and supraventricular tachycardia
slide69
Verapamil (Calan, Verelan, Isoptin)
  • Diltiazem (Cardizem, Dilacor, Tiazac)
slide70

Adverse effects include:

  • headache
  • Dizziness
  • GI disturbances
  • orthostatic hypotension
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