Pharmacology: Cardiac Arrhythmia Drugs

Question 1

What is the generalised action of class 1 drugs?

Answer 1

They block Na channels. 
This slows conduction of phase 0 but has minor effects on the action potential duration.
1A  has moderate affects on phase 0 
1B has no change in phase 0 
1C has marked effects on phase 0

Question 2

What is the action of class 2 drugs?

Answer 2

Beta-blockers prevent entry of calcium during phase 2 of the action potential.
This diminishes the phase 4 depolarisation

Question 3

What is the action of class 3 drugs?

Answer 3

Block K channels.
Therefore the depolarisation occurs more slowly - the refractory period is prolonged so the cell cant be excited for long. Increases the overall action potential duration.

Question 4

What is the action of class 4 drugs?

Answer 4

Block calcium channels
There is a decrease in the phase 4 spontaneous depolarisation. There is no change in the duration of the action potential.

Question 5

What is the action of class 4 drugs on the slow action potential?

Answer 5

Calcium channels blockers

Decrease the gradient of the slope 0 which lengthens the refractory period

Question 6

Describe the ways in which abnormal impulse generation can arise

Answer 6

Automatic rhythms:
Enhance normal - sinus tachycardia where there is increase APs from the SA node.
Ectopic focus - APs arise from sites other than the SA node.

Triggered rhythms: (abnormal depolarisation)
Delayed afterdepolarisation - arises from the resting potential
Early afterdepolarisation - arises from the plateau eg before the repolarisation is complete

Question 7

Describe the abnormal conduction patterns

Answer 7

Conduction block: the impulse is not conducted from the atria to the ventricles. Can be 1st 2nd or 3rd degree.

Re-entry rhythms:
There is a unidirectional block where the impulse can travel retrograde

Abnormal anatomy:
Accessory pathway called the bundle of Kent, leads to WPW

Question 8

What is the principle action of drugs used to treat arrhythmias caused by abnormal generation?

Answer 8

Decrease the phase 4 slow in the pacemaker cells. This slows conduction and increases the threshold.

Question 9

What is the principle action of drugs used to treat arrhythmias caused by abnormal conduction?

Answer 9

• decrease the conduction velocity by decreasing slope of phase 0
• increase the effective refractory period so the cell wont be excited again

Question 10

Name the class 1A agents

Answer 10

Procainamide
Quinidine
Disopyramide

Question 11

What are the specific actions of class 1A agents?

Answer 11

• decrease conduction by decreasing phase 0 of AP
• increase refractory period by enhancing Na inactivation
• decrease automaticity by decreasing slpe of phase 4
• increasing threshold

Question 12

What are the effects of 1A agents on ECG?

Answer 12

Increased QRS
Prolonged PR interval
Prolong QT interval

Question 13

What are the uses of class 1A agents?

Answer 13

Not commonly used.
Quinidine - maintain sinus rhythm in AF and atrial flutter and prevent recurrence
Procainamide - IV treatment of supraventricular and ventricular rhythms

Question 14

What are the side effects of class 1A agents?

Answer 14

hypotension 
reduced CO 
dizziness 
confusion 
insomnia 
seizure (high doses)
GI effects common 
Lupus-like syndrome esp procainamide 
Can actually be pro-arrhythmic

Question 15

Name the class 1B agents

Answer 15

Lidocaine - IV only

Mexiletine - oral

Question 16

What are the specific actions of 1B agents?

Answer 16

AP duration slightly decreased
Increased threshold of APs
Decrease phase 0 in fast beating or ischaemic tissue but not normal tissue

Question 17

What is the effect of 1B agents on ECG?

Answer 17

None in normal.

In fast or ischaemic tissue - increased QRS

Question 18

What are 1B agents used for?

Answer 18

ventricular tachycardia esp during ischaemia

Question 19

What are the side effects of 1B agents?

Answer 19

Safer than 1A due to less risk of pro-arrhythmia
CNS - drowsiness, dizziness
Gi upset common

Question 20

Name the class 1C agents

Answer 20

Flecainide
Propafenone
Can be used orally or IV

Question 21

What are the effects of 1C agents?

Answer 21

• substantial decrease of phase 0
• decreased automaticity by increasing threshold
• increase AP duration and refractory period esp in rapidly depolarising atrial tissue (AF)

Question 22

What are the effects of 1C agents on ECG?

Answer 22

Increased PR interval
Increased QRS
Increased QT

Question 23

What are class 1C agents used for?

Answer 23

Wide spectrum:

• AF and atrial flutter
• premature ventricular contractions
• WPW

Question 24

What are the side effects of 1C agents?

Answer 24

Flecainide - chronic use can cause pro-arrhythmias and sudden cardiac death (contraindicated if previous MI)
CNS and GI upsets

Question 25

``` Name the class 2 agents? What are the routes of administration? ```

Answer 25

Propanolol - oral or IV Bisoprolol - long acting oral Metoprolol - Oral or IV Esmolol - IV only, half life 9 mins

Question 26

What are the effects of class 2 agents?

Answer 26

Increased AP duration and refractory period in AV node to slow AV node conduction velocity Decrease phase 4 depolarisation

Question 27

What are the effects of class 2 agents on the ECG?

Answer 27

Increased PR interval | Decreased heart rate

Question 28

What are the uses of class 2 agents?

Answer 28

- sinus tachycardia - catecholamine tachycardia - protecting the ventricles from high atrial rates such as AF

Question 29

What are the side effects of class 2 agents?

Answer 29

Bronchospasm - need to be careful in asthma | Hypotension

Question 30

Name the class 3 agents

Answer 30

Amiodarone - oral or IV, half life 3 months | Sotalol

Question 31

What are the cardiac effects of amiodarone?

Answer 31

Affect all phases of the cardiac AP - increase refractory period - decrease phase 0 - increase threshold - decrease phase 4 - decrease speed of AV conduction

Question 32

What are the effects of amiodarone on the ECG?

Answer 32

Increased PR interval Increased QRS Increased QT Decreased HR

Question 33

What is amiodarone used for?

Answer 33

Very wide spectrum - effective for most arrhythmias

Question 34

What are the side effects of amiodarone?

Answer 34

Side effects can be serious and the risks increase with chronic use ~3years - pulmonary fibrosis - hepatic injury (monitor warfarin) - increased LDL - thyroid disease (contains iodine) - photosensitivity (need to wear factor 50) - optic neuritis which can cause transient blindness

Question 35

What are the effects of sotalol?

Answer 35

Increased AP duration and refractory period Slows phase 4 Slows AV conduction

Question 36

What are the ECG effects of sotalol?

Answer 36

Increased QT | Decreased HR

Question 37

What are the uses of sotalol?

Answer 37

A step down from amiodarone | Wide spectrum - supraventricular and ventricular tachycardia

Question 38

What are the side effects of sotalol?

Answer 38

Can be pro-arrhythmic Fatigue Insomnia Prolonged QT

Question 39

Name the class 4 agents

Answer 39

Verapamil - oral or IV | Diltiazem - oral

Question 40

What are the effects of class 4 agents?

Answer 40

Slow conduction through the AV node Increase refractory period in AV node Increase slope of phase 4 in SAN to slow HR

Question 41

What are the effects of class 4 agents on ECG?

Answer 41

Increased PR interval | HR can increase or decrease depending on the BP and baroreflex

Question 42

What are the uses of class 4 agents?

Answer 42

Control the ventricles during supraventricular tachycardia

Question 43

What are the side effects of class 4 agents?

Answer 43

Constipation | Need to be cautious in partial AV block, can get asystole if there is also a beta blocker taken

Question 44

What is the mechanism of action of adenosine?

Answer 44

IV bolus with a half life of seconds Binds to A1 receptors and activates K+ currents in AV and SAN. Causes hyperpolarisation which decreases HR and increases refractory period. Get decreased calcium currents

Question 45

What is adenosine used for?

Answer 45

To slow AV conduction - convert re-entrant supraventricular arrhythmias - hypotension during surgery

Question 46

What is the action and effects of vernakalant?

Answer 46

Given as an IV bolus over 10 mins to block atrial specific K channels. Slows atrial conduction (increased potency with higher HR) which can convert recent onset AF to normal sinus rhythm.

Question 47

What is the action and use of ivabradine?

Answer 47

Given orally. Blocks funny current in SA node so slows the node but doesnt affect BP (unlike beta blockers) Used tor reduce sinus tachy and reduce HR in heart failure and angina - avoiding BP drops

Question 48

How does digoxin work? What is it used for?

Answer 48

Enhances vagal activity, slows AV conduction and slows HR. | Used to reduce ventricular rates in AF and atrial flutter

Question 49

What is the action and use of atropine?

Answer 49

Its a selective muscarinic antagonist which blocks vagal activity to speed Av conduction and increase HR Used to treat vagal bardycardia

Question 50

Which drugs can be used to treat AF?

Answer 50

``` Rate control (act at AV node) Bisoprolol or verapamil for asthmatics, diltiazem. Digoxin can be an add on therapy. ``` Rhythm control Sotalol, if acute give IV flecainide with bisoprolol or amiodarone

Question 51

What IV drugs can be used for VT?

Answer 51

Metoprolol Lignocaine Amiodarone but need to inform of risks and side effects Choice of above 3 depends on drugs already prescribed

Question 52

Should flecainide be used alone in atrial flutter?

Answer 52

No - need to also give an AV node blocker | If the conduction of the atria is reduced the AV node may take the new rate leading to faster ventricular rate

Question 53

What is the best treatment for WPW?

Answer 53

Ablation can cure. Flecainide is 1st line, oral or IV Amiodarone can be used but inform of risks and side effects

Question 54

List the drugs that can be used in re-entrant supraventricular tachycardia

Answer 54

Acute (IV): Adenosine (dont use in asthma) Verapamil Flecainide ``` Chronic (oral): In order of line: - bisoprolol, verapamil - sotalol - flecainide, procainamide - amiodarone ```

Question 55

What drugs can be used for ectopic beats?

Answer 55

1st line is bisoprolol If fails can use flecainide, sotalol or amiodarone NB flecainide should never be used in previous MI, ischaemia or structural heart disease

Question 56

What drugs can treat sinus tachycardia?

Answer 56

Ivabradine - v specific, no drop in BP but do not use in pregnancy, teratogenicity unknown Bisoprolol, verapamil - safer but drops BP