Pharm. of Drugs Affecting Arrhythmias

Question 0

In the Singh-Vaughan Williams classification scheme, what do class II drugs do?

Answer 0

Class II are beta-blockers

Question 1

In the Singh-Vaughan Williams classification scheme, what do class I drugs do?

Answer 1

Block Na+ channels (local anesthetics) - slow conduction velocity and reduce excitability.

Question 2

In the Singh-Vaughan Williams classification scheme, what do class III drugs do?

Answer 2

Class III drug are K+ channel blockers: prolong refractoriness, but don’t reduce excitability.

Question 3

In the Singh-Vaughan Williams classification scheme, what do class IV drugs do?

Answer 3

Class IV drugs are Ca++ channel blockers (L-type Ca++ channels)

Question 4

In the Singh-Vaughan Williams classification scheme, what do class IA drugs do?

Answer 4

block both Na+ and K+ channels

Question 5

Name 1 class IA drug to remember?

Answer 5

Procainamide

Question 6

Name 1 class IB drug to remember?

Answer 6

Lidocaine

Question 7

Name 1 class IC drug to remember?

Answer 7

Flecainide

Question 8

How do class IA, IB, and IC vary in their effects on the Na+ channel?

Answer 8

IB are weakest
IC are intermediate
IA are most potent

Question 9

What’s one class II drug (aka beta blocker) used for arrhythmias?

Answer 9

Atenolol

Question 10

What’s one class III drug to remember?

Answer 10

Dofetilide (specific K+ channel inhibitor)

Question 11

What’s one class IV drug (aka. Ca++ blocker) to remember?

Answer 11

Verapamil

Question 12

Aside from it’s effects on the Na/K pump, how can digoxin affect arrhythmias?

Answer 12

It’s a muscarinic agonist as well.

Question 13

What Singh-Vaughan Williams classes of drugs can be used to treat V Tach?

Answer 13

Class I - Na+ blockers
Class III - K+ blockers
(both slowing conduction/decreasing excitability AND prolonging refractoriness counteract V Tach)

Question 14

What Singh-Vaughan Williams classes of drugs can be used to treat A Fib?

Answer 14

Class I - Na+ blockers
Class III - K+ blockers
(both slowing conduction/decreasing excitability AND prolonging refractoriness counteract A Fib)

Question 15

What Singh-Vaughan Williams classes of drugs can be used to treat AV reentry?

Answer 15

Class I - Na+ blockers
Class II - beta blockers
Class III - K+ blockers

Question 16

What Singh-Vaughan Williams classes of drugs can be used to treat AV nodal reentry?

Answer 16

Class II - beta blockers
Class IV - Ca++ blockers
Others: digoxin and adenosine

Question 17

What 3 parameters can you modify with drugs to affect reentrant tachycardias?

Answer 17

Excitability (class I), conduction velocity (class I), and effective refractory period (class III)

Question 18

What parameter can you modify with drugs to affect automaticity?

Answer 18

Phase 4 depolarization

Question 19

Which parameter is modified by drugs that predispose to tachycardias due to early afterdepolarizations?

Answer 19

Prolonged action potential duration.

Class III drugs, i.e. K+ blockers, do this… and thus predispose to Torsade des pointes

Question 20

How does HR modify the effect of Na+ channel blockade?

Answer 20

Faster HR -> the drugs block the channels more.

Question 21

How does membrane potential affect the ability of Class I drugs to block Na+ channels? How is this relevant to choosing a drug in ischemia-related arrhythmia?

Answer 21

More depolarized -> easier to block.
In ischemia, myocytes are more depolarized.
Lidocaine, being class IB and less potent, will thus selectively block Na+ channels in ischemic myocytes.

Question 22

3 parameters that increase the potency of K+ blockers in prolonging action potential duration (APD)?

Answer 22

Slow HR
Low extracellular K+ (makes sense. If there’s less K+, blocking it’s movement will have greater relative effect)
Low extracellular Mg++

Question 23

What 2 ions do you want to target when dealing with arrhythmia caused by “fast response” tissue i.e. myocytes & His-Purkinje system?

Answer 23

Na+ and K+

Thus, Class I and Class III drugs.

Question 24

What 4 surface molecules can you target when trying to deal with arrhythmias generated by "slow response" tissue i.e. SA and AV nodes?

Answer 24

``` Beta receptors (causes decreased Ca++ current - I(Ca) ) Ca++ channels Muscarinic receptors (decreased I(Ca), increased I(KAch) ) Adenosine receptors (decreased I(Ca), increased I(KAch) ) ```

Question 25

Class II, Class IV, digoxin, and adenosine all have what effect on SA rate, AV node ERP, and AV node excitability?

Answer 25

All decrease SA rate Increase AV node effective refractory period Decrease AV node excitability

Question 26

If you want to prolong ERP in fast response tissue, what do you use? In slow response tissue?

Answer 26

Fast response: block K+ | Slow response: block Ca++ (or other drugs that indirectly lower Ca++)

Question 27

Do drugs distinguish between cardiac and vascular smooth muscle Ca++ channels?

Answer 27

Yep.

Question 28

What's a Ca++ blocker specific for cardiac Ca++ channels?

Answer 28

Verapamil

Question 29

What's a Ca++ channel blocker specific to vascular smooth muscle Ca++ channels? (what would this do?)

Answer 29

Nifedipine (this drug dilates blood vessels -> rapid and dramatic drops in SVR and BP)

Question 30

What's a Ca++ blocker that affects both cardiac tissues and vascular smooth muscle?

Answer 30

Diltiazem

Question 31

What drug would you give to most rapidly address a tachycardia caused by slow response tissue?

Answer 31

Adenosine | people used to give IV Varapamil

Question 32

Would a K+ blocker better address a reentry tachycardia with a "short" or "long" excitability gap?

Answer 32

Class IA and III drugs work for short excitability gaps (I guess they can... get rid of them completely, stopping the reentry circuit). They don't work if the excitability gap is too long.

Question 33

Can class I drugs cause reentry to get started?

Answer 33

Yes, by making the slow path slower.

Question 34

(This lecture doesn't have much internal consistency...) Can you also target the AV node (with beta blockers, Ca++ blockers, digoxin, adenosine) to treat AVRT?

Answer 34

Apparently. (wasn't mentioned earlier... apparently you can use any of these antiarrhythmia drugs for AVRT???)

Question 35

You've got someone in AVRT and you give them sotolol (class III + beta blocker). This fixes the arrhythmia, with an initial disappearance of the P wave. Where did the block occur?

Answer 35

The block occurred in the bypass tract - the conduction couldn't get back up to the atria to cause atrial depolarization (P wave).

Question 36

You've got someone in AVRT and you give them esmolol (beta blocker). This fixes the arrhythmia - it ends on a P wave that isn't followed by a QRS. Where did the block occur?

Answer 36

The block occurred at the AV node.

Question 37

Can you treat post-MI ventricular tachycardia with lidocaine?

Answer 37

No, you need a more potent Na++ blocker. | surviving fibers aren't necessarily ischemic, but they're slow because of reduced gap junctions -> reentry circuit

Question 38

What classes of drugs CAN'T you use for AVNRT?

Answer 38

Class I and III. You want to target the slow response tissue of the AV node... using beta blockers (class II), Ca++ blockers (class IV), digoxin, or adenosine. (IV verapamil or adenosine for acute, others for prevention)

Question 39

2 factors predisposing for A Fib? (there are probably others) Why?

Answer 39

It's all about the wavelets: allow them more room, or make the wavelengths smaller. Enlarged atria. (more area -> more possibility for wavelet microcircuits) Alcohol -> shortens effective refractory period -> shortened wavelength.

Question 40

What's the equation for electrical wavelength (relevant to A fib)?

Answer 40

Wavelength = ERP * conduction velocity

Question 41

What are 2 places you target when treating A Fib? Drugs that do this?

Answer 41

``` The atria - prolong the ERP so the wavelets don't fit. (class I and III) The AV node - prolong the ERP so fewer impulses are transmitted. (class II, IV, digoxin) ```

Question 42

Treatment for Torsade des pointes?

Answer 42

Remove IA and III drugs. Give isoproterenol to increase HR. Pacing.

Question 43

4 conditions that raise risk of using anti-arrhythmia drugs?

Answer 43

``` Long QT (genetic, low K+ or Mg++) Sick sinus syndrome (SA node too slow) AV block Poor systolic function (you should be able to figure out which drugs make which worse) ```