Antiarrhythmic 2 Flashcards
1
Q
What are the Class IC drugs and what is their effect?
A
Flecainide / Propafenone
• Markedly depress Phase 0 of action potential
→ marked slowing of conduction of action potential but, little effect on duration or ventricular effective refractory period
- Associate and re-associate slowly with Na+ channels
- Show prominent effects even at normal heart rates
2
Q
Class 1C Drug Map
A
- no effect on potassium channels
- only effect by blocking sodium channels: increase QRS
3
Q
What are the clincial Applications of Flecainide?
A
Severe symptomatic ventricular arrhythmias, premature ventricular contraction or ventricular tachycardia resistant to other therapy
Severe symptomatic supraventricular arrhythmias & prevention of paroxysmal atrial fibrillation
Flecainide and propafenone are associated with the potential for fatal ventricular arrhythmias in persons with structural heart disease.
4
Q
What are the adverse effects of Flecainide?
A
- Negative inotropic efffect (aggravates CHF)
- CNS effects: dizziness, blurred vision, headache
- GI effects: nausea, vomiting, diarrhea
- Life-threatening arrhythmias & ventricular tachycardia
5
Q
What is the Clinical Applications and adverse effects of Propafenone?
A
• Used for treatment of life-threatening ventricular arrhythmias and the maintenance of normal sinus rhythm in patients with symptomatic atrial fibrillation
Adverse Effects
- Similar to flecainide
- Also has b-blocking activity therefore bronchospasm, aggravation of underlying heart failure etc.
6
Q
Class 1 a,b,c Summary:
A
7
Q
What are the common features of Class II antiarrhythmic drugs?
A
b-blockers
• Reduce both heart rate & myocardial contractility (b1)
- Slow conduction of impulses through myocardial conducting system
- Reduce rate of spontaneous depolarization in cells with pacemaker activity (block of adrenergic release)
• Little effect on action potential in most myocardial cells
8
Q
Class II Map
A
- prolong repolarization through the av node
- Slow conduction through the AV node
- increase in PR
9
Q
Propranolo, Metoprolol Clinical Applications
A
- Reduce incidence of sudden arrhythmic death after MI
- Control of supraventricular tachycardias (atrial fibrillation & flutter, AV nodal re-entrant tachycardias)
- Ventricular tachycardias (catecholamine-induced arrhythmias, digoxin toxicity)
10
Q
Esmolol Clinical applications:
A
- Short-acting b1-selective antagonist
- t1/2 = ~ 9 min
- Used IV for treatment of acute arrhythmias occurring during surgery or in emergency situations
11
Q
Class II adverse effects:
A
Propranolol / Metoprolol / Esmolol
- Bradycardia, hypotension, CNS effects etc.
- Contraindicated in acute CHF, severe bradycardia or heart block and severe hyperactive airway disease
12
Q
Common features of class III
A
K+ channel blockers
- Block repolarizing K+ channels
- Prolong action potential (and QT interval) without altering Phase 0 or resting membrane potential
- Prolong effective refractory period
- All have potential to induce arrhythmias
13
Q
Class III map
A
- prolong repolarization
- Increase in QT
14
Q
Amiodarone Mechanism of Action?
A
- Related structurally to thyroxine (contains iodine)
- Complex MOA showing Class I, II and III (& some IV) effects
- Dominant effect = K+ channel blockade.
- Decreases AV conduction & sinus node function.
- Blocks mostly inactivated Na+ channels
- Weak Ca2+ channel blocker
- Inhibits adrenergic stimulation (a & b-blocking properties)
• Antianginal & antiarrhythmic activity
15
Q
Amiodarone Clincal Applications
A
- One of most commonly employed antiarrhythmics(despite side-effect profile)
- Used in the management of ventricular & supraventricular arrhythmias
- Amiodarone is the drug of choice for acute VT refractory to cardioversion shock.
- Low doses for maintaining normal sinus rhythm in patients with atrial fibrillation
16
Q
Amiodarone Adverse Effects?
A
- Long term use = > 50% patients show adverse effects severe enough for discontinuation
- Many are dose-related and reversible on decreasing dose eg, interstitial pulmonary fibrosis, GI intolerance, tremor, ataxia, dizziness, hyper- or hypothyroidism, liver toxicity, photosensitivity, neuropathy, muscle weakness, hypotension, bradycardia, AV block, arrhythmias
- blue skin discoloration (iodine accumulation)
- despite prolonging the QT interval, has low incidence of Torsades de Pointes.
17
Q
Amiodarone Contraindications:
A
• Patients taking: Digoxin, theophylline, warfarin, quinidine
- Patients with:
- Bradycardia
- SA or AV block
- Severe hypotension
- Severe respiratory failure
18
Q
Sotalol Mechanism of Action?
A
- Potent non-selective b-blocker
- Inhibits rapid outward K+ current
- Prolongs repolarization & duration of action potential
• Lengthens refractory period
19
Q
Sotalol Clinical Applications:
A
- Treatment of life-threatening ventricular arrhythmias
- Maintenance of sinus rhythm in patients with atrial fibrillation & flutter who are currently in sinus rhythm
- Due to pro-arrhythmic effects – do not use for asymptomatic arrhythmias
20
Q
Sotalol Adverse effects?
A
- As for b-blockers
- Lowest rate (of antiarrhythmics) of acute or long-term adverse effect
- Torsades de pointes (prolongs QT interval)
- Use with caution in patients with renal impairment
21
Q
A
22
Q
Dofetilide clincal applications:
A
• Potent and pure K+ channel blocker
Clinical Applications
Conversion of atrial fibrillation / flutter to normal sinus rhythm
Maintenance of normal sinus rhythm in patients with chronic atrial fibrillation / flutter of longer than one week duration who have been converted to normal sinus rhythm
23
Q
Dofetililde?
A
Adverse Effects
- Headache, chest pain, dizziness, ventricular tachycardia
- Torsade de Pointes (prolongs QT interval)
24
Q
What are the common features of Class 4?
A
- Ca2+ channel blockers
- Decrease inward Ca2+ current leads to decreased rate of Phase 0 depolarization
- Slow conduction in tissues dependent on Ca2+ current (SA & AV nodes)
- Major effects on both vascular & cardiac smooth muscle
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Class 4 Map
* increase PR
26
Verapamil and Diltiazem features and major effects?
* Verapamil = relatively selective for the myocardium and is less effective as a systemic vasodilator drug
* Diltiazem = intermediate selectivity for the myocardium between verapamil and the dihydropyridines
Major Effects:
• Decrease contractility (negative inotropy)
• Decrease heart rate (negative chronotropy)
• Decrease conduction velocity (negative dromotropy)
27
Verapamil and diltiazem mechanism of action?
* Inhibit voltage-sensitive Ca2+ channels → decrease in slow inward current that triggers cardiac contraction
* Bind only to open, depolarized channels, preventing repolarization before drug dissociates
* Use/state-dependent
* Slow conduction & prolong effective refractory period
28
Verapamil and diltiazem clinical applications?
• More effective against **atrial** than ventricular arrhythmias
**• Supraventricular tachycardia is major arrhythmia indication**
**• Reduction of ventricular rate in atrial fibrillation & flutter**
• Hypertension, angina
29
Verapamil and diltiazem adverse effects and contraindications?
* Negative inotropes
* Transient decrease in BP
* CNS effects (headache, fatigue, dizziness)• GI effects (constipation, nausea)
Contraindications: Verapamil can increase the concentrations of other cardiovascular drugs such as digoxin, dofetilide, simvastatin, & lovastatin
30
Digoxin common features:
* Shortens refractory period in atrial & ventricular myocardial cells
* Prolongs effective refractory period & diminishes conduction velocity in AV node
Clinical Applications: Control of ventricular response rate in atrial fibrillation & flutter with impaired left ventricular function or heart failure
31
Digoxin mechanism of action?
• **Heart Failure** :Positive inotrope (increases intracellular [Ca2+]i)
* **Arrhythmias**
* Direct AV node blocking effects & vagomimetic properties:
* Inhibition of Ca2+ currents in AV node
* Activation of Ach-mediated K+ currents in atrium
**• Major indirect actions**
• Hyperpolarization
• Shortening of atrial action potentials• Increases in AV nodal refractoriness
32
Digoxin Antiarrhythmic effect?
(1) Slows AV conduction,
and
(2) Prolongs effective refractory period of the AV node
thereby decreasing the fraction of atrial impulses that are conducted through the node and increasing PR interval
→ useful in treating atrial flutter / fibrillation (by controlling ventricular rate)
33
Digoxin Adverse effect?
Toxic doses
• Ectopic ventricular beats → ventricular tachycardia & fibrillation
34
Adenosine common feature?
* Naturally occurring nucleoside (P1 receptor agonist)
* High doses = decreases conduction velocity & prolongs refractory period as well as decreasing automaticity in AV node
* Very short t1/2 (15 s)
35
Adenosine mechanism of action
* Enhances K+ conductance
* Inhibits cAMP-mediated Ca2+ influx
* Leads to hyperpolarization esp. in AV node
Clinical Applications: IV adenosine = drug of choice for abolishing acute supraventricular tachycardia
36
Adenosine Adverse effect?
Low toxicity
* Flushing
* Burning
* Chest pain
* Hypotension
• Bronchoconstriction in asthmatics (may persist up to 30 min)
37
Magnesium common feature?
• Functional Ca2+ antagonist
Used for treatment of:
• Torsades de pointes
* Digitalis-induced arrhythmia
* Prophylaxis of arrhythmia in acute MI
38
Atropine effect?
Used in bradyarrhythmias to decrease vagal tone
39
What are the Anti-Arrhythmic Drug Action Summary
40
Anti-Arrhythmic Classified by Cardiac Tissue on which they act
41
Anti-Arrhythmic Classified by Arrhythmia on which they are effective
42
What is Atrial Fibrillations?
* Can be paroxysmal (intermittent) or persistent (chronic)
* For most patients is not immediately life-threatening, management is focused mainly on symptom control & prevention of long-term morbidity & mortality
Treatment Approaches:
* Rhythm control (restore and maintain sinus rhythm)
* Rate control (control of ventricular rate while allowing atrial fibrillation to continue)
43
Rate vs Rhythm Control?
Rate control - Generally involves drugs that act on AV node to slow conduction
Rhythm control -Achieved either by synchronized direct current or by drugs (both methods must be preceded by anticoagulation)
44
Drug Therapy in Rate Control?
1. Rate control (slowing of ventricular rate) - negative dromotropic agents
* Ca2+ channel blockers
* b-blockers
* Digoxin (in patients with reduced EF or CHF)
* Amiodarone (when other agents can’t be used)
45
Drug Therapy in Rhythm Control?
2. Rhythm control (induction / maintenance of sinus rhythm)
* Class IC antiarrhythmics, (flecainide, propafenone)
* Class III antiarrhythmics, (amiodarone, dofetilide)
46
What are the prevention methods used in Thromboembolic Events?
* Heparin (IV) -Unstable patients who require immediate cardioversion
* Warfarin (oral)- In stable patients cardioversion should be delayed for 3- 4 weeks until adequate anticoagulation has been achieved
* Control of ventricular rate should be undertaken whilst patient is waiting for cardioversion
* Oral anticoagulants usually continued for at least 4 weeks after procedure
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