Antiarrhythmic Drugs

Question 1

Singh-Vaughan Williams Classification

Answer 1

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

Question 2

8 Prototypical drugs and their actions

Answer 2

1. 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*

Question 3

Which Singh-Vaughan Williams classifications affect fast vs slow response tissue?

Answer 3

• I and III: fast response (Na, K affected) -II and IV: slow response (Ca affected)

Question 4

General mechanisms of drugs that affect reentrant tachycardias, automaticity, and tachycardia due to early afterdepolarizations

Answer 4

-Reentrant: drug effects on excitability, ERP, conduction velocity -Automaticity: drug effects on phase 4 depolarization -Early Afterdepolarizations: drugs that prolong ventricular APD

Question 5

Effects of Class I and III drugs on Fast Response tissue

Answer 5

Question 6

Main effect of blocking K channels

Answer 6

-prolong APDs (this is most impactful in fast response tissues)

Question 7

Factors that modify the strength of Na channel blockade

Answer 7

• 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)

Question 8

Factors that increase the effect of I-K blockade on APD

Answer 8

• slow heart rates
• low Extracellular K
• low extracullar Mg

** important bc pts can be on diuretic and low in K and Mg

Question 9

Pathways for drug action in slow response tissue: atenolol, verapamil, digoxin, adenosine

Answer 9

Question 11

Atenolol, varapamil, digoxin, adenosine drug effects on slow response tissue

Answer 11

Question 12

Determinants of ERP in fast and slow response tissue

Answer 12

• fast: basically, APD since Na channels recover very quickly
• slow response: longer than APD, since Ca channels take time to reopen after the APD

Question 13

Selectivity of Ca Channel blockers and Vascular Calcium Channels

Answer 13

• verapamil: cardium
• Nifedipine: vascular
• Diltiazem: cardiac and vascular

Question 14

Recap the 4 drugs discussed that act on slow response tissue

Answer 14

1. atenolol
2. verapamil
3. digoxin
4. adenosine

Question 15

Differences between drugs that act on slow response tissue ( recall these are important since they all have same effects on tissue)

Answer 15

Question 16

Tachycardias due to reentry

Answer 16

1. reentry in a fixed circuit AVNRT, AVRT, VT in healed infarct
2. reentry with multiple shifting wavefronts: A and V fib

Question 17

3 conditions needed for reentry

Answer 17

1. potential path
2. unidirectional block
3. slow conduction

Question 18

2 mechanisms and classes of drugs which cause conduction block

Answer 18

1. Decrease excitability: Class I drugs via fixed bidirectional block
2. Increase ERP: Class IA or III drugs: block due to refractoriness

Question 19

How the length of the excitable gap affects reentry termination by IA or III drugs (increase ERP)

Answer 19

1. short excitable gap will be terminated bc refractoriness can be extended throughout the short gap
2. long excitable gap: reentry is not terminated; cannot extend ERP long enough

Question 20

2 strategies for terminating reentry in FAST RESPONSE reentrant circuit, classes of drugs, necessary substrates, and risks associated

Answer 20

1. Prolong ERP to cause refractory block: Ia, III; short excitable gap, risk with excessively long APD leading to EADs and torsade de points
2. decreased excitability to cause fixed block: IA, IB, IC; need low safety factor, risk that slow conduction can actually facilitate reentry

Question 21

AV Reentrant Tachycardia

Answer 21

Question 22

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)?

Answer 22

• 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.

Question 23

In general, what meds could be used to block a AVRT?

Answer 23

• IA or III drugs causing blocking in bypass tract
• adenosite, atenolol, or digoxin causing block due to prolonged refractoriness in AV node

Question 24

Ventricular Tachycardia post MI

Answer 24

-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

Question 25

What is abnormal about the ventricular cells post MI?

Answer 25

-they have disrupted gap junctions and therefore have slow conduction, but they have normal shaped APs

Question 26

AVNRT

Answer 26

Question 27

Electrical wavelength: what is it?

Answer 27

-length of refractoriness: ERPx conduction velocity

Question 28

Atrial fibrillation

Answer 28

Question 29

Torsades des pointes

Answer 29

Question 30

Drugs that affect cardiac rhythm that are used for nonarrhythmic indications

Answer 30

1. HTN: Ca channel blockers, B blockers 2. Systolic dysfunction: Beta blockers, digoxin 3. Ischemia: B blockers, Ca channel blockers

Question 31

4 conditions that rase the risk of using antiarrhythmic drugs

Answer 31

1. Prolonged QT, especially with low K, Mg: risk of torsade des points with class Ia or III 2. Sick Sinus syndrome: worse sinus bradycardia with II, IV, Digoxin, and amiodarone 3. AV block: higher degree AV block with II and IV, class I and II drugs slow junctional pacemaker 4. Poor systolic function: I, II, IV are all negatively inotropic

Question 32

Using antiarrhythmic drugs safely: monitoring drug treatment

Answer 32

1. during drug initiation, monitor high risk patients and correct reversible risk factors like low Mg or K 2. 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)

Question 33

Drug of choice for AVNRT

Answer 33

- adenosine: short half life - atenolol, verapamil, digoxin most appropriate for longterm arrhythmia suppression

Question 34

What is the most common arrhythmia treated with antiarrhythmic drugs?

Answer 34

- A fib - enlarged atrium is common substrate

Question 35

2 targets and drugs for A fib

Answer 35

1. 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 2. terminate atrial fibrillation: prolong ERP in atria with procainamide, dofetilide, sotalol, amiodarone

Question 36

In clinical practice, what is the most common cause of torsades des pointes?

Answer 36

- 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

Question 37

Torsades des pointes can be either _____ or \_\_\_\_\_\_. It may degenerate to \_\_\_\_\_\_.

Answer 37

- sustained or nonsustained - can degenerate to v fib and death

Question 38

What drugs from this lecture are considered to cause QT prolongation and a risk for torsade des pointeS?

Answer 38

-Class Ia and III drugs

Question 39

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.

Answer 39

- purkinje fibers - ventricular muscle

Question 40

How minimize risk for Class Ia and III drugs from causing torsades des pointes

Answer 40

- started in ECG monitored setting - correct electrolyte abnormalities by low K and low Mg

Question 41

Sinus tachycardia can be caused by \_\_\_\_\_\_, \_\_\_\_\_\_, \_\_\_\_\_\_\_, \_\_\_\_\_\_\_, and _______ in addition to exercise. In these situations, treatment should be directed at ...

Answer 41

- hypotension - hypoxia - anemia - hyperthyroidism - anxiety - treat underlying cuase

Question 42

Comparing utility of lidocaine vs flecainide

Answer 42

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.