Rx- Antiarrhythmics Flashcards
This plateau in cardiac depolarization causes
ventricular contraction to last as much as ____
times longer than skeletal muscle
contractions from a single action potential
15
Phase 4
Resting membrane potential
Phase 0
Depolarization
■ When the cell is stimulated, voltage-gated
sodium channels open quickly and permit
sodium to rush in, depolarizing the cell
membrane extremely quickly.
Phase 1
- Initial Repolarization
■ The voltage-gated sodium channels rapidly
close. By this time, voltage-gated potassium
channels are open, allowing potassium to rush
out of the cell, causing some repolarization.
Phase 2
The Plateau
■ L-Type Calcium Channels that open slowly
during Phases 0 and 1 allow calcium to rush in. This influx of calcium balances the efflux of
potassium from early potassium channels,
thereby extending depolarization (plateau)
Phase 3
- Rapid Repolarization
■ L-Type Calcium Channels close and additional potassium channels open, permitting potassium to exit the cell at a faster rate, causing rapid repolarization of the membrane.
Some genetic mutations can result in abnormalities in channel proteins
in the heart, further resulting in arrhythmogenic syndromes
■ An example is_____
familial prolonged QT syndrome
The most commonly used classification system for the antiarrhythmic drugs
Vaughan-Williams classification
Modified Vaughan-Williams Classification of Antiarrhythmic Medications:
○ Class 1 - Sodium Channel Blockers (split up into three subclasses)
○ Class 2 - Beta Blockers
○ Class 3 - Potassium Channel Blockers
○ Class 4 - Calcium Channel Blockers
○ (Class 5 - Variable mechanisms; miscellaneous group)
Class 1 Agents & subcategories
Class 1 antiarrhythmic medications act by modulating or
blocking the sodium channels that are responsible for rapid depolarization.
○ Class 1A - Increase duration of PR, QRS, and QT
○ Class 1B - Increase QRS duration, shorten AP duration
○ Class 1C - Increase duration of PR and QRS, not AP
Class 1A Agents
● Procainamide, Quinidine, and Disopyramide
Class 1A Agents MOA
○ Sodium Channel Blocker - Presumably interact with specific amino acids
in the internal pore of the sodium channel.
○ These depress Phase 0, thereby slowing QRS depolarization.
○ These also have moderate Potassium channel blocking activity, which
tends to slow the rate of the repolarization and prolongs the overall
action potential duration (Increases duration of PR, QRS, and QT)
○ These also seem to have a little anticholinergic activity and tend to
depress myocardial contractility
Indications for Class 1A agents
○ Supraventricular Tachycardias
○ Ventricular Tachycardia
○ Quinidine only- Severe Malaria
Contraindications for Class 1A agents
○ Systemic Lupus Erythematosus (Procain.)
○ 2nd or 3rd Degree AV Block
○ Congenital QT prolongation
BBWs of Class 1A agents
○ Procainamide: Proarrhythmic effects can
occur; advised to restrict use
to life-threatening ventricular
arrhythmias.
■ Can cause positive ANA tests,
w/ or w/o Sxs of SLE.
■ Can cause blood dyscrasias;
check CBC qwk x 3 months.
○ Quinidine and Disopyramide: Increased mortality in Tx of non-life-threatening arrhyth.
Class 1A Agents SA
○ Urinary retention, dry mouth, constipation (especially with Disopyramide)
○ Hypotension
○ Reversible Lupus Syndrome (with long-term Procainamide; 30%)
■ Increased ANA (50%)
Major Adverse Reactions of Class 1A agents
○ At slower heart rates, potassium channel blockade may predominate, leading to
even longer action potential duration and the QT interval, resulting in increased
automaticity. Widened QT can result in Torsades.
○ Ventricular fibrillation and Asystole.
○ Severe blood dyscrasias can occur with Procainamide and Disopyramide.
○ Complete AV blocks can occur with Quinidine
Follow Up for Class 1A agents
○ Dose adjustments needed if renal and/or hepatic impairment.
○ Check electrolytes, CBC, and ANA at baseline.
■ Repeat CBC weekly for 3 months with Procainamide
○ Lots and lots of drug interactions - Always run through checker.
○ Pregnancy/Lactation: Caution advised, but no harm expected
a treatment of choice for AVRT (SVT in WPW)
Class 1A agents
Class 1B Agents
Lidocaine and Mexiletine
Class 1B Agents MOA
○ Sodium Channel Blocker - Presumably interact with specific amino acids
in the internal pore of the sodium channel.
○ These have less prominent sodium channel blocking activity at rest, but
effectively block the sodium channel in depolarized tissues.
■ For this reason, they seem to be more effective with
tachyarrhythmias than with slow arrhythmias
○ They also seem to shorten repolarization to some extent.
■ Shortens the action potential duration and the QT interval
Class 1B Agents Indications
○ Ventricular Tachycardia and Fibrillation (Lidocaine used in ACLS)
○ Lidocaine: Local anesthesia
○ Mexiletine: *Off-label use of diabetic neuropathic pain
Class 1B Agents Contraindications
○ Cardiogenic shock
○ AV Blocks
○ Lidocaine: Wolff-Parkinson-White syndrome
BBWs of Class 1B agents
Mexiletine: Excessive mortality or nonfatal cardiac arrest rate in nonlife-threatening arrhythmias. Restrict use to life-threatening vent. arrhythmias.
Class 1B Agents SAs
○ GI upset
○ Nausea
○ Anxiety
○ Lightheadedness
○ Tremor
○ Palpitations
○ Headache
○ Tinnitus
Major Adverse Reactions of Class 1B agents
○ Ventricular arrhythmias
○ Lidocaine:
■ CNS depression or seizures
■ Coma
■ Heart block
■ Respiratory depression or arrest
■ Bradycardia and hypotension
Follow Up for Class 1B agents
○ EKG should be monitored continually during Lidocaine infusion.
○ Monitor vital signs closely.
○ Check electrolytes at baseline.
○ Lidocaine may be used during pregnancy and lactation.
■ Mexiletine, however, should be used with caution
Pearl for Class 1B agents
When injecting lidocaine for local anesthesia purposes, it’s important to not inject into a major vessel because it’s an antiarrhythmic drug
Class 1C Agents
Flecainide and Propafenone
Class 1C Agents MOA
○ Sodium Channel Blocker - Presumably interact with specific amino acids
in the internal pore of the sodium channel.
○ These primarily block open sodium channels, depressing Phase 0
depolarization and slowing conduction (QRS prolongation).
○ They dissociate slowly during diastole, resulting in increased effect at
more rapid rates. This is the basis of their antiarrhythmic efficacy,
especially against supraventricular arrhythmias
○ These both have mild potassium channel blocking activity as well, but
do not significantly change the action potential duration.
Class 1C Agents indications
○ Ventricular Arrhythmias (VT and VF) prevention
○ Supraventricular Tachycardia prevention (A-Fib and PSVT)
