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Anti-Arrhythmia Agents Flashcards

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1
Q

What are the 5 phases of the cardiac action potential?

A

0: Upstroke
1: Early-fast repolarization
2: Plateau
3: Repolarization
4: Diastole

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2
Q

Ion Movements Phase 0

A

Na influx

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3
Q

Ion Movements Phase 1

A

K efflux (Transient Outward)

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4
Q

Ion Movements Phase 2

A

Ca influx - counterbalances the K efflux to maintain a plateau period

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5
Q

Ion Movements Phase 3

A

K efflux (Delayed Rectifier)

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6
Q

Ion Movements Phase 4

A

Na/K ATPase Pump

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7
Q

What is the refractory period in atrial and ventricular myocytes determined by?

A

Voltage

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8
Q

What is the refractory period in pacemaker cells determined by?

A

Time

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9
Q

What are the general types of arrhythmias?

A
  • Too fast
  • Too slow
  • Asynchronous
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10
Q

What are the causes of arrhythmias?

A
  1. disturbed impulse formation
  2. disturbed impulse conduction
  3. combination of 1 and 2
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11
Q

What are some examples of disturbed impulse formation?

A 
Early afterdepolarization (EAD)
Delayed afterdepolarization (DAD)
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12
Q

What are some examples of disturbed impulse conduction?

A

SA-block
AV-block
Re-entry

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13
Q

What are the requirements for re-entry?

A
  • Slowed conduction
  • Conduction block
  • Unidirectional block
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14
Q

What are the aims of anti-arrhythmic therapy?

A

Aimed to reduce ectopic pacemaker activity and/or

modify conduction characteristics to disable re-entry circuits

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15
Q

Use-dependent or state-dependent drug action

A

Drug has highest binding affinities to the activated and inactivated channels with low to no affinity for the resting state.

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16
Q

What should be done for the treatment of asymptomatic or minimally symptomatic arrhythmias?

A

Treatment should be AVOIDED

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17
Q

Class I

A

Na+ Channel Blockers

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18
Q

Class II

A

ß-adrenoceptor blockers

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19
Q

Class III

A

Prolong AP Duration

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20
Q

Class IV

A

Ca2+ Channel Blockers

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21
Q

What is a secondary effect of Na+ Channel Blockers?

A

Local anesthesia

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22
Q

What is the general action of the Class I agents?

A

Reduction of conduction velocity by reducing rate and magnitude of depolarization via Na+ channel blockade.

May influence repolarization through effects on K+ channels which will prolong the AP duration.

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23
Q

Class I A

A

Intermediate kinetics, APD is increased

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24
Q

Class I B

A

Fast kinetics, APD is decreased

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25
Class I C
Slow kinetics, APD remains the same
26
Examples of Class I A
Procainamide, Quinidine, Disopyramide
27
Examples of Class I B
Lidocaine, Mexiletine
28
Examples of Class I C
Flecainide, Propafenone
29
Procainamide Actions
- Slows upstroke of AP, conduction, prolongs QRS complex - Direct depressant actions on SA and AV nodes - More effective in depolarized cells (use/state dependent action)
30
Procainamide Indications
Atrial and ventricular arrhythmias - Drug of second or third choice though
31
Procainamide SE
Ganglion blocking properties, Risk of hypotension Anti-cholinergic effects Induction of torsade de pointes arrhythmia
32
Quinidine Actions
Same as procainamide - Slows upstroke of AP, conduction, prolongs QRS complex - Direct depressant actions on SA and AV nodes - More effective in depolarized cells (use/state dependent action)
33
Quinidine Indications
Same as procainamide Atrial and ventricular arrhythmias - Rarely used though
34
Quinidine SE
Ganglion blocking properties, risk of hypotension Anti-cholinergic effects, increases sinus rate and AV conduction Induction of ventricular fibrillation and torsade de pointes Cinchonism: headache, dizziness, tinnitus
35
Lidocaine Actions
No effect on conduction, recovery from block between action potential selective depression of conduction in depolarized (ischemic) cells
36
Lidocaine Indications
Drug of 1st choice for treatment of ventricular tachycardia and fibrillation after cardioversion in the setting of ischemia/infarction
37
Lidocaine ROA
IV only
38
Lidocaine SE
Least cardiotoxic among Class I drugs | Large doses may induce hypotension probably through effects on myocardial contractility
39
Mexiletine Actions
Orally active lidocaine analogue | Actions/adverse effects similar to lidocain
40
Mexiletine Indications
Off label use for chronic pain
41
Flecainide Actions
Potent blocker of Na+ and K+ channels with slow kinetics No anti-cholinergic effects
42
Flecainide Indications
Supraventricular arrhythmias in patients with otherwise normal hearts
43
Flecainide SE
Increases mortality in patients with ventricular tachyarrhythmias, myocardial infarction and ventricular ectopy
44
Propafenone Actions
Potent blocker of Na+ channels with slow kinetics, may also block K+ channels Structural similarity to propranolol with weak -blocking activit
45
Propafenone Indications
Supraventricular arrhythmias in patients with otherwise normal hearts
46
Propafenone SE
Probably same as flecainide (arrhythmogenic) Sinus bradycardia/bronchospasm (ß-blockade) Metallic taste and constipation
47
What are the non-selective Class II agents?
Propranolol (other: Sotalol, Timolol)
48
What are the selective Class II agents?
Esmolol (other: Acebutolol)
49
What are the actions of the Class II agents?
Inhibit sympathetic influences on cardiac electrical activity Reduce heart rate Decrease intracellular Ca++ overload Decrease pacemaker currents
50
Class II Agent Indications
Prevention of recurrent infarction and sudden death after myocardial infarction Exercise-induced arrhythmias Also used for atrial fibrillation, atrial flutter and AV nodal reentry
51
Class II Agent SE
Bradycardia Bronchospasm Hypoglycemia (masked in diabetics)
52
Class III Agent Actions
Class III drugs typically block K+ currents (Ikr) responsible for Phase 3 repolarization and the delayed repolarization causes prolongation of action potential duration and prolongation of refractory period.
53
What is the EKG finding with Class III agents?
QT Prolongation
54
Amiodarone Actions
- Dominant effect is prolongation of action potential duration - Blocks K+ and Na+ channels, weakly blocks Ca++ channels and inhibits ß-receptors - Prolongs refractoriness and slows conduction, suppresses abnormal automaticity and can slow normal sinus automaticity - Prolongs QT interval and QRS complex
55
Amiodarone Indications
1st choice drug for recurrent ventricular tachycardia or fibrillation resistant to other drugs, also used for atrial fibrillation
56
What is amiodarone an analog of?
Thyroid Hormone
57
Amiodarone SE
Pulmonary toxicity (pulmonary fibrosis in 1%) Cornea microdeposits in almost all patients Blocks conversion of T4 to T3, source of inorganic iodine:
58
Dronedarone Actions
- Structural analogue of amiodarone without iodine atoms | - Amiodarone like effects
59
What are the advantages of dronedarone over amiodarone?
- As yet, no thyroid or pulmonary toxicity noted
60
Dronedarone Indications
Atrial fibrillation/flutter
61
Dronedarone Contraindications
Contraindicated in severe or recently decompensated symptomatic heart failure
62
What are the types of Class IV agents?
Dihydropyridines Benzothiazepine Phenylalkylamine
63
Nifedipine and Nitrendipine Indications
High vascular selectivity | Used for hypertension
64
Diltiazem Indications
Used for hypertension, angina pectoris and arrhythmia
65
Verapamil Actions
Blocks activated and inactivated Ca++ channels primarily in the heart, exhibits use/state-dependent action. Directly slows AV nodal conduction and increases AV node refractoriness slows SA node automaticity Lowers heart rate and increases PR-interval
66
Verapamil Indications
``` Supraventricular arrhythmias (drug of 1st choice) Re-entry arrhythmias/tachycardias involving the AV node Slows ventricular rate in atrial flutter/fibrillation ```
67
Verapamil SE
Vasodilation (particularly after bolus injection) and negative inotropic effects AV block in patients with AV nodal disease or in high doses
68
Verapamil Contraindications
ß-blockers | Patients with ventricular tachycardia
69
Adenosine Actions
- Acts via purinergic receptors (GPCR), increases K+ conductance (hyperpolarization) and inhibits cAMP-mediated Ca++ currents - Primarily acts on atrial tissues - Slows AV node conduction and increases AV node refractoriness - Produces transient cardiac arrest
70
Adenosine Indications
Drug of choice for conversion of paroxysmal supraventricular tachycardia to sinus rhythm
71
Adenosine SE
Flushing and shortness of breath, sinus bradycardia, sinus pauses, AV block, decrease in blood pressure
72
Adenosine PK
VERY short half life on the order of seconds - administered via bolus
73
What drugs should be used for the conversion to sins rhythm?
Adenosine / Amiodarone Flecainide
74
What drugs should be used for the maintenance of sinus rhythm?
Amiodarone / Dronedarone Flecainide / Propafenone
75
What drugs should be used for ventricular rate control?
Diltiazem / Verapamil / Propranolol / Esmolol
76
Ventricular tachycardia treatment
Amiodarone | Lidocaine
77
Ventricular fibrillation treatment
Defibrillation w/wo Amiodarone or Lidocaine
78
Atrial fibrillation treatment
Diltiazem/Verapamil Propranolol
79
Paroxysmal supraventricular tachycardia treatment
Adenosine/Amiodarone Verapamil/Diltiazem/ Propranolol
80
AV block (Io)/IIo/IIIo treatment
Atropine/Pacemaker

Pharmacology (74 decks)

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