How many classifications of antidysrhythmics drugs are there?
What is the mechanism of action for Class I?
Class I: sodium channel blockers
What is the mechanism of action for Class II?
Class II: beta blockers
What is the mechanism of action for Class III?
Class III: potassium channel blockers
What is the mechanism of action for Class IV?
Class IV: non-dihydropyridines
Class I antidysrhythmics have 3 subclasses. What is the MoA for each of them and name a drug or two that falls into the categories?
Class IA: prolong the action potential duration (quinidine, procainamide)
Class IB: shorten the action potential duration (lidocaine, phenytoin)
Class IC: decrease the rate of phase 0 depolarization (flecainide, propafenone)
What are some Class II drugs?
What are some Class III drugs?
What are some Class IV drugs?
What occurs during phase 0 of the ventricular myocyte?
Na rapidly enters the cell (AKA depolarization)
What occurs during phase 1 of the ventricular myocyte?
K and Cl move out of the cell the inward Na current rapidly decays (AKA the start of repolarization)
What occurs during phase 2?
Ca enters the cell, moving slowly K exits the cell these two balance out the membrane potential and cause the "plateau"
What occurs during phase 3?
Ca current decays K continues to exit the cell, eventually getting the cell back to its resting membrane potential
What occurs during phase 4?
slow K leak that keeps the membrane at its resting potential
What do all the phases look like?
What is the MoA of procainamide?
- Class IA antidysrhythmic drug
- Decreases the slope of phase 0 depolarization
- Lengthens the action potential duration and the effective refractory period (Na channel action) and lengthens the repolarization period (K channel blockade).
What is the indication for procainamide?
ventricular tachydysrhythmias and atrial tachydysrhythmias
(though not as effective as quinidine)
What are side effects of procainamide?
Hypotension (due to myocardial depression)
Ventricular asystole or fibrillation (when administered in the presence of heart block)
Ventricular dysrhythmias (in excess plasma levels)
Lupus like syndrome (present in slow acetylators)
Fever, rash, nausea, vomiting
What are the EKG changes seen with procainamide?
ST-T wave changes on the EKG
Prolongation of the QTc (similar but less than with quinidine)
Titrate to effect IV: 100-200 mg loading dose or 15-18 mg/kg infused slowly (over 15-20 minutes), may repeat q 5 minutes to effect.
Then a rate of 1-6 mg/min (Therapeutic levels are 4-8 micrograms/mL)
What is the MoA of lidocaine?
- delays the rate of spontaneous phase 4 depolarization by preventing or diminishing the gradual decrease in potassium ion permeability that normally occurs during this phase.
(Does not alter spontaneous phase 4 depolarization in atrial cardiac cells) [this was in S&H]
Indication for lidocaine?
- Suppression of ventricular dysrhythmias (having minimal effects on supraventricular tachydysrhthmias)
- Suppresses reentry cardiac dysrhythmias such as PVCs and VTach.
- Efficacy of prophylactic lido therapy for preventing early vfib after acute MI has not been documented and is no longer recommended.
Side effects of lidocaine?
- Bradydysrhythmias and asystole.
- Toxic doses (>5mcg/ml) produce peripheral vasodilation and direct myocardial depression, resulting in hypotension
- Seizures are possible at high doses
- CNS depression, apnea, and cardiac arrest at greater than 10mcg/ml
- Conculsive threshold is decreased during arterial hypoxemia, hyperkalemia, or acidosis
- If toxic, start IV lipid therapy. (per the book, but we know that this probably won't work)
EKG changes seen with lidocaine?
- No significant effect on QRS or QTc or on AV conduction
- May decrease conduction in AV node as well as bundle of HIS. (prolonged PR, widened QRS if toxic)
Dose for lidocaine?
- For people with normal cardiac and liver function 2mg/kg IV followed by a continuous infusion of 1-4 mg per minute.
- Decreased CO or hepatic blood flow (as with anesthesia, acute MI, CHF) decrease the dose by 50%.
What is the MoA of phenytoin (dilantin)?
- Class IB antidysrhythmic
-Reduces the slope/slows phase 4 depolarization by interfering with K+ permeability.
- Also reduces the slope/slows Phase 0 (phase characterized by RAPID influx of Na+) by preferentially blocking Na+ channels in rapidly-firing/depolarized myocardial tissue. This action slows the rate of myocardial depolarization. [per the book]
Indication for phenytoin?
- Classically used for ventricular dysrhythmias r/t digoxin toxicity*
- Paradoxical V-tach or torsades de pointes (prolonged QT)
- Ventricular dysrhythmias due to other causes (although less effective for this compared to quinidine, procainamide, or lidocaine)
Side effects of phenytoin?
hypotension when delivered rapidly in high doses
pain at injection site (very alkaline)
increased blood glucose d/t inhibition of insulin secretion
thrombocytopenia d/t depression of bone marrow
phenytoin toxicity typically at levels >18mcg/mL (symptoms: CNS/cerebellar disturbances – ataxia, nystagmus, vertigo, slurred speech, sedation, confusion)
EKG changes with phenytoin?
Shortens QT interval more than any other antidysrhythmic drug No significant effect on ST waves or QRS complex.
Improved AV node conduction SA node depression (volatile agents also depress SA node so be mindful of this if phenytoin is administered under general anesthesia)
1.5mg/kg (or 100mg) q5min
up to 15mg/kg (max 1000mg) IV