Antiarrhythmic Drugs Flashcards
Singh-Vaughan Williams Classification
Class I block Na channels: local anesthetics Class II: Beta blockers: block B receptor and downstream I ca, Ik, If -Class III: K channel blockers (delayed rectifier) -Class IV: Ca channel blockers
8 Prototypical drugs and their actions
- Procainamide: IA, INa and IK 2. Lidocaine IB: I Na 3. Flecainide: IC; I Na 4. Atenolol: II; Beta blockers, ICa, Ik, If 5. Dofetilide: III; Ik 6. Verapamil: IV; ICa 7. Digoxin* 8. Adenosine*
Which Singh-Vaughan Williams classifications affect fast vs slow response tissue?
- I and III: fast response (Na, K affected) -II and IV: slow response (Ca affected)
General mechanisms of drugs that affect reentrant tachycardias, automaticity, and tachycardia due to early afterdepolarizations
-Reentrant: drug effects on excitability, ERP, conduction velocity -Automaticity: drug effects on phase 4 depolarization -Early Afterdepolarizations: drugs that prolong ventricular APD
Effects of Class I and III drugs on Fast Response tissue
Main effect of blocking K channels
-prolong APDs (this is most impactful in fast response tissues)
Factors that modify the strength of Na channel blockade
- subclasses: 1B lead potent, IA intermediate, IC most potent
- RMP: more potent in cells with depolarized RMP (arrythmic tissue is depol so this is helpful)
- Heart rate: more potent at fast heart rates (tachy)
Factors that increase the effect of I-K blockade on APD
- slow heart rates
- low Extracellular K
- low extracullar Mg
** important bc pts can be on diuretic and low in K and Mg
Pathways for drug action in slow response tissue: atenolol, verapamil, digoxin, adenosine
Atenolol, varapamil, digoxin, adenosine drug effects on slow response tissue
Determinants of ERP in fast and slow response tissue
- fast: basically, APD since Na channels recover very quickly
- slow response: longer than APD, since Ca channels take time to reopen after the APD
Selectivity of Ca Channel blockers and Vascular Calcium Channels
- verapamil: cardium
- Nifedipine: vascular
- Diltiazem: cardiac and vascular
Recap the 4 drugs discussed that act on slow response tissue
- atenolol
- verapamil
- digoxin
- adenosine
Differences between drugs that act on slow response tissue ( recall these are important since they all have same effects on tissue)
Tachycardias due to reentry
- reentry in a fixed circuit AVNRT, AVRT, VT in healed infarct
- reentry with multiple shifting wavefronts: A and V fib
3 conditions needed for reentry
- potential path
- unidirectional block
- slow conduction
2 mechanisms and classes of drugs which cause conduction block
- Decrease excitability: Class I drugs via fixed bidirectional block
- Increase ERP: Class IA or III drugs: block due to refractoriness
How the length of the excitable gap affects reentry termination by IA or III drugs (increase ERP)
- short excitable gap will be terminated bc refractoriness can be extended throughout the short gap
- long excitable gap: reentry is not terminated; cannot extend ERP long enough
2 strategies for terminating reentry in FAST RESPONSE reentrant circuit, classes of drugs, necessary substrates, and risks associated
- Prolong ERP to cause refractory block: Ia, III; short excitable gap, risk with excessively long APD leading to EADs and torsade de points
- decreased excitability to cause fixed block: IA, IB, IC; need low safety factor, risk that slow conduction can actually facilitate reentry
AV Reentrant Tachycardia
How can you tell if AVRT was corrected using a medication that blocked the bypass tract (Class I or III) or AV node (II, IV)?
- If inverted P wave disappears after last QRS complex, the reentry path was targeted with a Class IA or III drug like sotalol
- If you still see an inverted P wave after last QRS, the AV node was targeted with a drug like esmolol.
In general, what meds could be used to block a AVRT?
- IA or III drugs causing blocking in bypass tract
- adenosite, atenolol, or digoxin causing block due to prolonged refractoriness in AV node
Ventricular Tachycardia post MI
-Ia, Ic, III: lidocaine is not helpful bc these cells are post MI are have normal RMP; IB are not potent enough for cells with normal RMP but would be more helpful in cell in acute ischemic attach which are depolarized
What is abnormal about the ventricular cells post MI?
-they have disrupted gap junctions and therefore have slow conduction, but they have normal shaped APs
AVNRT
Electrical wavelength: what is it?
-length of refractoriness: ERPx conduction velocity
Atrial fibrillation
Torsades des pointes
Drugs that affect cardiac rhythm that are used for nonarrhythmic indications
- HTN: Ca channel blockers, B blockers
- Systolic dysfunction: Beta blockers, digoxin
- Ischemia: B blockers, Ca channel blockers
4 conditions that rase the risk of using antiarrhythmic drugs
- Prolonged QT, especially with low K, Mg: risk of torsade des points with class Ia or III
- Sick Sinus syndrome: worse sinus bradycardia with II, IV, Digoxin, and amiodarone
- AV block: higher degree AV block with II and IV, class I and II drugs slow junctional pacemaker
- Poor systolic function: I, II, IV are all negatively inotropic
Using antiarrhythmic drugs safely: monitoring drug treatment
- during drug initiation, monitor high risk patients and correct reversible risk factors like low Mg or K
- during chronic therapy, monitor for unwanted EP effects or drug toxicity: ECGs from sinus brady, AV block, long QT and blood tests for amiodarone toxicity (liver, thyroid)
Drug of choice for AVNRT
- adenosine: short half life
- atenolol, verapamil, digoxin most appropriate for longterm arrhythmia suppression
What is the most common arrhythmia treated with antiarrhythmic drugs?
- A fib
- enlarged atrium is common substrate
2 targets and drugs for A fib
- slow AV node to slow ventricular rate: prolong ERP of AV node with atenolol, verapamil, digoxin. Adenosine could do this but is very short acting and not useful for the long term
- terminate atrial fibrillation: prolong ERP in atria with procainamide, dofetilide, sotalol, amiodarone
In clinical practice, what is the most common cause of torsades des pointes?
- administration of a drug that prolongs the ventricular AP and QT interval on ECG
- also due to bradycardia, long paused after Premature beat, and low serum K and Mg
Torsades des pointes can be either _____ or ______. It may degenerate to ______.
- sustained or nonsustained
- can degenerate to v fib and death
What drugs from this lecture are considered to cause QT prolongation and a risk for torsade des pointeS?
-Class Ia and III drugs
Torsade des pointes is thought to be due to triggered activity due to early afterdepolarizations. This arrythmias occurs when APs in _____ or _______ are very prolonged and instead of repolarizing, give rise to a single or repetitive depolarizations from reduced membrane potential.
- purkinje fibers
- ventricular muscle
How minimize risk for Class Ia and III drugs from causing torsades des pointes
- started in ECG monitored setting
- correct electrolyte abnormalities by low K and low Mg
Sinus tachycardia can be caused by ______, ______, _______, _______, and _______ in addition to exercise. In these situations, treatment should be directed at …
- hypotension
- hypoxia
- anemia
- hyperthyroidism
- anxiety
- treat underlying cuase
Comparing utility of lidocaine vs flecainide
Among sodium channel blockers there is a hierarchy of effects. IB drugs, like lidocaine, are weak sodium channel blockers. I A drugs, like procainamide, are intermediate in potency. IC drugs, like flecainide, are potent sodium channel blockers.
In addition to these effects the extent of sodium channel blockage is modified by heart rate and resting membrane potential. Faster heart rate and depolarized (less negative) resting potential both increase sodium channel blockade. As a result of these effects, lidocaine, a 1A drug with weak sodium channel blockade, does not depress conduction velocity and excitability at normal heart rates in normal cells but does depress conduction velocity and excitability in sick depolarized cells such as during acute ischemia. In contrast, Flecainide, a IC drug with potent sodium channel blockage, depresses conduction velocity and excitability even in normal cells at normal heart rates. These effects are enhanced by depolarized tissue and fast heart rates.
