Quinidine
Class Ia
- Na+ channel blocker
- also blocks K+ channels (K+ rectifier)
- state dependent—> selectively depresses tissue that is frequently depolarized
- decrease slope of phase 0 depolarization of cardiac muscle
- prolongs phase 3 repolarization
- increases threshold for firing in abnormal pacemaker cells
- higher affinity for open Na+ channels than inactivated channels
MOA
↑AP Duration
↑effective refractory period
↑QT (TdP risk)
Indications
- atrial/ventricular arrhytmias
- re-entrant V-tach & SVT
Toxicity
- Cinchonism (headache, tinnitus, dizziness, blurred vision)
- thrombocytopenia
*Hyperkalemia causes increased toxicity for all class I drugs—> prolongs QT interval even further by prolonging depolarization
Procainamide
Class Ia
- Na+ channel blocker
- also blocks K+ channels (K+ rectifier)
- state dependent—> selectively depresses tissue that is frequently depolarized
- decrease slope of phase 0 depolarization of cardiac muscle
- prolong phase 3 repolarization
- increases threshold for firing in abnormal pacemaker cells
- higher affinity for open Na+ channels than inactivated channels
MOA
↑AP Duration
↑effective refractory period
↑QT (TdP risk)
Indications
- atrial/ventricular arrhytmias
- re-entrant V-tach & SVT
Toxicity
- pseudo-lupus (arthralgia and butterfly rash on face–> no anti DNA antibodies)
- thrombocytopenia
*Hyperkalemia causes increased toxicity for all class I drugs—> prolongs QT interval even further by prolonging depolarization
Disopyramide
Class Ia
- Na+ channel blocker
- also blocks K+ channels (K+ rectifier)
- state dependent—> selectively depresses tissue that is frequently depolarized
- decrease slope of phase 0 depolarization of cardiac muscle
- prolongs phase 3 repolarization
- increases threshold for firing in abnormal pacemaker cells
- higher affinity for open Na+ channels than inactivated channels
MOA
↑AP Duration
↑effective refractory period
↑QT (TdP risk)
Indications
- atrial/ventricular arrhytmias
- re-entrant V-tach & SVT
*Hyperkalemia causes increased toxicity for all class I drugs—> prolongs QT interval even further by prolonging depolarization
Lidocaine
Class IIb
- Na+ channel blocker
- preferentially blocks inactive channels
- dissociates from channel very fast
- decreases slope of phase 0 depolarization of cardiac muscle
- less than type Ia and Ic - preferentially affects ischemic tissue because lacks enough ATP to operate the Na/K+ pump to restore membrane potential, so the tissue is already party depolarized, therefore the Na+ are inactived
- also increases slope of phase 3 repolarization (faster)
- by blocking sodium channels, the cell can depolarize completely via K+ leaving the cell
MOA
↓ AP Duration,
↓ Effective refractory period
Indications
-acute ventricular arrhythmias POST MI!
Toxicity
CV depression
*Hyperkalemia causes increased toxicity for all class I drugs—> prolongs QT interval even further by prolonging depolarization
Flecainide
Class IIIc
-Na+ channel blocker
Propafenone
Class IIIc
- Na+ channel blocker
- high affinity for open channels and dissociates very slowly
- significantly prolongs phase 0 depolarization of cardiac muscle
- no effect on phase 3 depolarization (K+ channels)
- does not prolong QT interval
MOA
↑effective refractory period
Indications
-SVT including A-fib
Toxicity
-can cause arrhythmias post MI
contraindicated in structural and ischemic heart disease (Post MI)*
Propanolol
Acebutolol
Esmolol
Metoprolol
Class II
- acts on myocytes and SA/AV node
- anti arrhythmic effects due to their ability to inhibit sympathetic activations of cardiac automaticity and conduction
Myocytes:
↓ [Ca2+] = ↓ contractility
SA/AV nodes:
↓cAMP & Ca2+
-Slow inward Ifunny currents decreasing phase 4 depolarization slope and thus HR
*AV node particularly sensitive–> ↑PR interval
Indications
- ventricular rate control during a-fib or atrial flutter
- SVT
Toxicity
- exacerbation of COPD and asthma
- masks the signs of hypoglycemia
Contraindicated in cocaine users–risk of unopposed alpha-adrenergic receptor agonist activity
*treat overdose with glucagon
Amiodarone
Class I, II, III, and IV effects (Classified as III)
-blocks K+ rectifier currents (outward) that depolarize the heart during phase 3 of the action potential
-
Also:
-blocks Na+ channels
-blocks CA2+ channels (prolongs phase 2 plateau)
-blocks B-adrenergic receptors
MOA
- decreases SA node automaticity (decrease HR)
- decrease AV node conduction velocity (increase PR interval)
- prolongs AV node and ventricular refractory period (decrease HR)
- ↑PR interval
- ↑ QT interval (TdP risk)
- slight prolongation of QRS duration
Indications
- atrial fib
- atrial flutter
- ventricular tachycardia
**Used when other antiarrhythmics fail
Toxicity
- pulmonary fibrosis
- hepatotoxicity
- thyroid derangement
- corneal deposits
- blue/gray skin deposits
*always check PFT, LFT, TFT
Sotalol
Class III
- nonselective B adrenergic antagonist
- also blocks K+ rectifier currents
- slows depolarization (phase 3)
MOA
- prolongs cardiac action potential duration
- ↑ QT interval (TdP risk)
- ↑ effective refractory period
- decreases automaticity
- slows AV node conduction velocity (↑ PR interval)
- increases AV node refractory period
*no effect on ventricular conduction velocity or QRS duration!
Indications
- afib
- atrial flutter
- ventricular arrhythmias
**Used when other antiarrhythmics fail
Toxicity
-bronchospasm (excessive B-adrenergic blockade)
Ibutilide
Class III
- blocks K+ rectifier currents
- slows depolarization (phase 3)
MOA
- prolongs ventricular repolarization
- ↑ QT interval (TdP risk)
- ↑ effective refractory period
Indications
- rapid conversion of atrial fib or flutter to normal sinus rhythm
- does not affect HR, BP, QRS duration, or PR interval
**Used only when other anti-arryhythmics fail
Toxicity
Torsades de pointes
Dofetilide
Class III
- blocks K+ rectifier currents
- slows depolarization (phase 3)
MOA
- prolongs ventricular repolarization
- ↑ QT interval (TdP risk)
- ↑ effective refractory period
Indications
- rapid conversion of atrial fib or flutter to normal sinus rhythm
- does not affect HR, BP, QRS duration, or PR interval
**Used only when other anti-arryhythmics fail
Toxicity
Torsades de pointes
Verapamil
Class IV
- calcium channel blocker
- decreases slope of pacemaker phase 0 depolarization (decreases conduction velocity)
MOA
- decrease AV node conduction velocity
- increase AV node refractory period
- increase PR interval
- increase effect refractory period in AV node - much smaller effect on SA node and HR
- little effect on ventricular conduction velocity and refractory period
Indications
- prevention of nodal arrhythmias (SVT)
- rate control in A-fib with RVR
Toxicity
- constipation
- flushing
- edema
Diltiazem
Class IV
- calcium channel blocker
- decreases slope of pacemaker phase 0 depolarization (decreases conduction velocity)
MOA
- decrease AV node conduction velocity
- increase AV node refractory period
- increase PR interval
- increase effect refractory period in AV node - much smaller effect on SA node and HR
- little effect on ventricular conduction velocity and refractory period
Indications
- prevention of nodal arrhythmias (SVT)
- rate control in A-fib with RVR
Toxicity
- constipation
- flushing
- edema
