Drugs Used in Cardiac Arrhythmias Flashcards
Class 1 Sodium Channel-blocking Drugs: 1A
– Quinidine (Cardioquin)
– Procainamide (Pronestyl)
– Disopyramide (Norpace)
Class 1 Sodium Channel-blocking Drugs: 1B
– Lidocaine (Xylocaine)
– Mexiletine (Mexitil)
Class 1 Sodium Channel-blocking Drugs: 1C
– Flecainide (Tambocor)
– Propafenone (Rythmol)
Class 2 Beta Blockers
– Esmolol (Brevibloc)
– Propranolol (Inderal)
Class 3 Potassium Channel-blocking Drugs
– Amiodarone (Cordarone)
– Sotalol (Betapace)
– Dofetilide (Tikosyn)
– Ibutilide (Corvert)
Class 4 Cardioactive Calcium Channel Blockers
– Verapamil (Isoptin)
– Diltiazem (Cardizem)
Miscellaneous agents
Adenosine (Adenocard)
Fast action potential in cardiac muscle: Which phase?
- Voltage-dependent fast Na+ channels open as a result of depolarization; Na+ enters the cells down its electrochemical gradient
Phase 0
Fast action potential in cardiac muscle: Which phase?
- K+ exits cells down its gradient, while fast Na+ channels close, resulting in some repolarization
Phase 1
Fast action potential in cardiac muscle: Which phase?
- plateau phase results from K+ exiting cells offset by and Ca2+ entering through slow voltage-
dependent Ca2+ channels
Phase 2
Fast action potential in cardiac muscle: Which phase?
- Ca2+ channels close and K+ begins to exit more rapidly resulting in repolarization
Phase 3
Fast action potential in cardiac muscle: Which phase?
- Resting membrane potential is gradually restored by Na+/K+ ATPase and the Na+/Ca2+
exchanger
Phase 4
Effects of Class 1A drugs
- Block sodium channels
- Bind to open (ACTIVATED) sodium channels
- Dissociate from channel with INTERMEDIATE kinetics
- Block POTASSIUM channels
- PROLONG AP duration **
- Prolong QRS and QT intervals of the ECG **
Class 1A: Procainamide
Clinical Use?
• Used infrequently (frequent dosing is required,
common occurrence of lupus-related side effects)
• Is effective in sustained VENTRICULAR TACHYCARDIAS and arrhythmias associated with myocardial infarction (not
a first choice drug for these indications)
• Sidenote: it directly depresses the activities of SA and AV nodes
Class 1A: Procainamide
Adverse effects?
• Cardiac – QT interval prolongation – Induction of torsade de pointes arrhythmias and syncope – Excessive inhibition of conduction
• Extracardiac
– Lupus erythematosus syndrome with arthritis, pleuritis, pulmonary disease, hepatitis and fever
– Nausea, diarrhea
– Agranulocytosis
Class 1A: Quinidine
Pharmacodynamics and clinical use?
– Affords antimuscarinic effect on the heart –> may ENHANCE AV conductance
– Exhibits beta-blocking activity (effect on PR interval is
variable)
– May cause HYPOTENSION –> tachycardia
Class 1A: Quinidine
Clinical use?
Rarely used because of cardiac and extracardiac adverse
effects and the availability of better-tolerated antiarrhythmic drugs
Class 1A: Quinidine
Adverse effects?
• Cardiac:
– QT interval prolongation
– Induction of torsade de pointes arrhythmia and
syncope
– Excessive slowing of conduction throughout the
heart
• Extracardiac:
– GI side effects (diarrhea, nausea, vomiting)
– Headache, dizziness, tinnitus (cinchonism)
– Thrombocytopenia, hepatitis, fever
Class 1A: Disopyramide
Clinical use?
Recurrent ventricular arrhythmias
Class 1A: Disopyramide
Adverse effects?
• Cardiac: QT interval prolongation, induction of torsade de pointes arrhythmia and syncope, negative inotropic effect – may precipitate heart failure, excessive depression of cardiac conduction
• Extracardaic: atropine-like symptoms – urinary
retention, dry mouth, blurred vision, constipation, exacerbation of glaucoma
Effect of Class 1B Drugs
- Block sodium channels
- Bind to INACTIVATED sodium channels (bind to depolarized cells)
- Dissociate from channel with fast kinetics
- SHORTEN the AP
- Do NOT block potassium channels
- Do NOT prolong AP or QT duration
Class 1B: Lidocaine
Clinical use?
Termination of ventricular tachycardia in the setting
of acute myocardial ischemia
Class 1B: Lidocaine
Adverse effects?
• The least toxic of all Class 1 drugs
• Cardiovascular: may cause HYPOTENSION in patients
with heart failure by inhibiting cardiac contractility, proarrhythmic effects are uncommon
• Neurological effects: paresthesias, tremor, slurred
speech, convulsions
Class 1B: Mexiletine
Clinical use?
• Ventricular arrhythmias
• To relieve chronic pain, especially pain due to
diabetic neuropathy and nerve injury
Class 1B: Mexiletine
Adverse effects?
- Tremor
- Blurred vision
- Nausea
- Lethargy
Effect of Class 1C Drugs
- Block sodium channels
- Bind to open (ACTIVATED) sodium channels
- Dissociate from channel with SLOW kinetics
- Block certain potassium channels **
- Do NOT prolong AP duration and QT interval duration of the ECG **
- Prolong QRS interval duration **
Class 1C : Flecainide
What channels does it block?
Blocks sodium and potassium channels
Class 1C : Flecainide
Clinical use?
In patients with otherwise normal hearts who have
supraventricular arrhythmias
Class 1C : Flecainide
Adverse effects?
• May be very effective in suppressing premature
ventricular contractions, but may cause severe exacerbation of ventricular arrhythmias when administered to
– Patients with preexisting ventricular
tachyarrhythmias
– Patients with a previous myocardial infarction
– Patients with ventricular ectopic rhythms
Class 1C : Propafenone
Clinical use?
Supraventricular arrhythmias in patients without structural disease
Class 1C : Propafenone
Adverse effects?
- Exacerbation of ventricular arrhythmias
- A metallic taste
- Constipation
Class 2 Beta-Blockers
Effect on AP?
• Slow action potential
– Sinoatrial node – decrease HR (increase RR interval)
– AV node – decrease AV conductance (increase
PR interval)
Class 2 Beta-Blockers:
Clinical use of propranolol in cardiac arrhythmias?
- Arrhythmias associated with stress and THYROID storm
- Atrial fibrillation and flutter
- Paroxysmal supraventricular arrhythmias
• Arrhythmias associated with MI
– Decrease mortality in patients with MI
Class 2 Beta-Blockers: Esmolol
Clinical use?
- Supraventricular arrhythmias
- Arrhythmias associated with thyrotoxicosis
• Myocardial ischemia or acute myocardial infarction
with arrhythmias
• As an adjunct drug in general anesthesia to control
arrhythmias in perioperative period
Adverse effects of Beta-blockers?
– Reduced cardiac output – Bronchoconstriction – Impaired liver glucose mobilization – Produce an unfavorable blood lipoprotein profile (increase VLDL and decrease HDL) – Sedation, depression – Withdrawal syndrome associated with sympathetic hyperresponsiveness
Contraindications to Beta-blockers?
– Asthma – Peripheral vascular disease – Raynaud’s syndrome – Type 1 diabetics on insulin – Bradyarrhythmias and AV conduction abnormalities – Severe depression of cardiac function
Class 3 Potassium Channel Blockers:
Effects of Class 3 drugs?
– Block potassium channels
– Prolong action potential duration
– Prolong QT interval on ECG
– Prolong refractory period
Class 3 Potassium Channel Blockers: Amiodarone
Clinical use?
- Recurrent ventricular tachycardia
* Atrial fibrillation
Class 3 Potassium Channel Blockers: Amiodarone
Effects on heart rate and conduction?
- Has calcium channel blocking activities
- Causes bradycardia and slows AV conduction
- Causes peripheral vasodilation (effect may be related to the action of the vehicle)
Class 3 Potassium Channel Blockers: Amiodarone
Adverse effects?
• Cardiac
- AV block and bradycardia
- Incidence of torsade de pointes is low as compared to
other Class 3 drugs
• Extracardiac
- Fatal pulmonary fibrosis
- Hepatitis
- Photodermatitis, deposits in the skin, gives blue-grey
skin discoloration in sun-exposed areas
- Deposits of drug in cornea and other eye tissues, optical
neuritis
- Blocks the peripheral conversion of thyroxine to
triiodothyronine, also a source of inorganic iodine in the
body – may cause HYPO- OR HYPERTHYROIDISM
Class 3 Potassium Channel Blockers: Sotalol
Clinical use?
• Treatment of life-threatening ventricular
arrhythmias
• Maintenance of sinus rhythm in patients with atrial
fibrillation
Class 3 Potassium Channel Blockers: Sotalol
Adverse effects?
- Depression of cardiac function
* Provokes torsade de pointes
Class 3 Potassium Channel Blockers: Dofetilide
Clinical use?
• Restore sinus rhythm in patients with atrial
fibrillation
• Maintain the sinus rhythm after cardioversion in
patients with atrial fibrillation
Class 3 Potassium Channel Blockers: Dofetilide
Adverse effects?
QT interval prolongation and increased risk of
ventricular arrhythmias
Class 3 Potassium Channel Blockers: Ibutilide
Clinical use?
Conversion of atrial flutter and atrial fibrillation to sinus rhythm
Class 3 Potassium Channel Blockers: Ibutilide
Adverse effects?
QT interval prolongation and increased risk of ventricular arrhythmias (patients require continuous ECG monitoring until QTc returns to baseline)
Effect of Class 4 L-type calcium channel blockers
• Block both ACTIVATED AND INACTIVATED L-type
calcium channels
• Active in slow response cells
- Decrease the slope of phase 0 depolarization
- Increase L-type Ca2+ channel threshold potential
- Prolong refractory period in AV node
• Slow sinoatrial node depolarization, cause
bradycardia
• Prolong action potential duration and conduction time in AV node
Effect of Class 4 L-type calcium channel blockers:
Clinical use?
- Termination and prevention of paroxysmal supraventricular tachycardia
- Ventricular rate control in atrial fibrillation and flutter
Effect of Class 4 L-type calcium channel blockers:
Adverse effects?
• Cardiac – Negative inotropy – AV block – Sinoatrial node arrest – Bradyarrhythmias – Hypotension
• Extracardiac
– Constipation (Verapamil)
Miscellaneous: Adenosine
Effects of Adenosine
– Activates potassium current and inhibits Ca2+ and
Funny currents, causing marked hyperpolarization and suppression of action potentials in slow cells
– Inhibits AV conduction and increases nodal refractory period
Miscellaneous: Adenosine
Clinical use?
Conversion to sinus rhythm in paroxysmal supraventricular tachycardia
Miscellaneous: Adenosine
Adverse effects?
• Shortness of breath
• Bronchoconstriction (both A1
and A2B adenosine receptors cause bronchoconstriction)
- Chest burning
- AV block
- Hypotension
