Antiarrhythmics Flashcards
What are non-VW agents used in arrhythmias?
Adenosine and digoxin
Describe the Vaughan Williams classification of antiarrhythmics
Class I = Na channel blockers Class II = Beta blockersC lass III = K channel blockers Class IV = CCBs Class V = variable mechanisms (adenosine, digoxin)
Class IA antiarrhythmics
Procainamide
Quinidine
Disopyramide
(Na channel blockers)
Class IB antiarrhythmics
Lidocaine Mexilitine (Na channel blockers)
Class IC antiarrhythmics
Flecainide Propafenone (Na channel blockers)
Which Class I antiarrhythmics should NOT be used after IC?
IA
Effects of Class IA drugs
- Reduces AP duration and ventricular refractoriness
- Increases repolarization
Effects of Class IB drugs
Shortens AP duration, ventricular refractoriness and repolarization
Effects of Class IC drugs
Markedly slows depolarization without affecting repolarization
Procainamide (class, indications, key features)
- Class IA Na channel blocker
- Stable monomorphic VT, VT w/accessory pathway, non-VT/VF arrest
- IV only!
Procainamide ADRs
- Peripheral vasodilation
- Hypotension
- Reflex tachy
- Arrest
How is procainamide metabolized? What is its half life?
- CYP2D6
- 2.5 to 8 hours (NAPA metabolite 5-9 hours)
How is procainamide dosed in renal and hepatic impairments?
- Lower loading dose in renal
- Cut all doses 50% in hepatic
What drugs interact with procainamide?
- Tricyclics
- SSRIs
- Opioids
Procainamide serious adverse events
- Heart block, widening QRS, Torsades
- Hepatotoxicity
- Drug induced lupus
Disopyramide (class, indications, key features)
- Class IA Na channel blocker
- Stable monomorphic VT, AF conversion
- Used as an alternative to procainamide
- A/w cardiogenic shock
How is disopyramide metabolized? What is its half life?
- CYP3A4, significant 1st pass
- Half life 4-10 hours
How is disopyramide dosed?
Weight based
When is disopyramide adjusted in renal impairment?
CrCl less than 40 mL/min
Disopyramide serious adverse events
- Torsades, HF, hypotension
- Xerostomia
- Urinary hesitancy
- Constipation
- Rash
Disopyramide contraindications
- AV block
- QT prolongation
- Cardiogenic shock
Disopyramide has significant ____ effects, so it should be avoided in patients with _____
- Anticholinergic
- Avoid in glaucoma and myasthenia gravis
Quinidine (class, indications, key features)
- Class IA Na channel blocker
- Maintenance of sinus rhythm when LV function is preserved
- NOT used for ventricular arrhythmias
How is quinidine metabolized?
- CYP3A4
- Metabolite has antiarrhythmic effects that need to be accounted for
Quinidine serious adverse events
- Arrhythmias, QT prolonged, Torsades
- GI issues
- Dizzy, HA, tremor
Quinidine contraindications
- WPW
- AV block
- Digitalis toxicity
- Myasthenia gravis
Lidocaine (class, indications, key features)
- Class IB Na channel blocker
- VT/VF when defib/epi fails and amiodarone unavailable
- Digoxin induced VT, monomorphic VT
- Efficacy is reduced over duration of arrest
- “Safest” of all Na channel blockers
What is the safest of all Na channel blockers?
Lidocaine
How is lidocaine metabolized? What is its half life?
- CYP1A2, hepatic blood flow determines rate (significantly impaired during arrest)
- 1.8 hours
Lidocaine serious adverse events
- Arrhythmias
- Seizure, tremor, paresthesias
Mexiletine (class, indications)
- Class IB Na blocker
- Used for conversion and maintenance when other agents fail
How is mexiletine metabolized? What is its half life?
- CYP2D6 and 1A2 (higher doses needed in smokers)
- Variable half life (6-17 hrs)
Mexiletine adverse events
- GI
- Dizziness
- Arrhythmias
- Tremor, ataxia
Mexiletine contraindications
AV block, cardiogenic shock
Flecainide (class, indications, key features)
- Class IC Na blocker
- SVT, AF induced VT
- Pill in pocket conversion to sinus rhythm, paroxysmal AF
How is flecainide metabolized? What is its half life?
- CYP2D6
- 7-14 hrs in healthy ppl
- 19-22 hrs post
- MI-27 hrs w/HF and repeated dosing
Flecainide serious adverse events
- AV/BBB, QT prolong
- Dizzy, HA, fatigue
- Dyspnea
Flecainide contraindications
RBBB, AV block, cardiogenic shock
Propafenone (class, indications, key features)
- Class IC Na blocker
- VT and conversion to sinus rhythm
- Structure similar to propranol
How is propafenone metabolized? What is its half life?
- CYP2D6 (extensive 1st pass)
- 5 to 8 hours
Propafenone serious adverse events
- AV block, Torsades, QT prolonged
- Dizzy and CNS issues
Propafenone contraindications
- Bradycardia, AV block, sick sinus
- Electrolyte depletion
- Decompensated HF, hypotension
What is unique about esmolol?
Ultra-short acting (effective duration 20-30 mins)
What is esmolol used for?
Intraoperative and perioperative tachycardias
What are the ADRs of esmolol?
- Hypotension (dose related)
- Diaphoresis
- Nausea
- Bradycardia, bronchospasm, seizure
Contraindications of esmolol
- Severe sinus bradycardia
- 2nd or 3rd degree AV block
- Cardiogenic shock
Propranolol and its uses
- Nonselective B blocker
- Used for acute rate control
- ER form used for long term rate control
How is propranolol metabolized and what is unique about its composition?
- CYP2D6 and 1A2 (extensive 1st pass effect)
- Highly protein bound
ADRs of propranolol
- Hypotension and bradycardia
- Raynaud’s
- Cognitive effects
- Dyslipid and dysglycemia
When is propranolol contraindicated?
Severe pulmonary and liver disease
What is nadolol and its uses?
- Nonselective B blocker
- 3rd or 4th line for rate control
- Other uses: HTN, CAD, variceal hemorrhage, thyroid storm
When is nadolol dosing adjusted?
Renal impairment
ADRs of nadolol
Same as propranolol
- Hypotension, bradycardia
- Raynaud’s
- Cognitive effects
- Dyslipid and dysglycemia
Contraindications for nadolol
Severe pulmonary disease
What is atenolol and its uses?
- Selective B1 blocker
- Acute VT and maintenance (unlabeled)
- Migraine proph, ETOH withdrawal, HTN, angina, hyperthyroid
How is atenolol metabolized?
- Limited hepatic metabolism
- Excreted unchanged in urine/feces
Half life of atenolol
6-7 hrs
When is dosing of atenolol adjusted?
Renal impairment
ADRs of atenolol
- Same as all other selective agents
- Hypotension, bradycardia
- Raynaud’s
- Cognitive effects
- Dyslipid and dysglycemia
What is metoprolol and its uses?
- Selective B1 blocker
- Acute VT and maintenance (unlabeled)
- Migraine proph, essential tremor, HTN, angina, cardiomyopathy, hyperthyroid
How is metoprolol metabolized?
Extensive hepatic (and 1st pass) via CYP2D6
ADRs of metoprolol
- Hypotension, bradycardia
- Raynaud’s
- Cognitive dysfunction
- Dyslipid and dysglycemia
What is carvedilol and its uses?
- Mixed alpha and beta blocker
- Labeled uses: HTN, angina, post MI LVD and HF
- Unlabeled: maintenance in some AF pts (post MI, stable LVD and HF)
Metabolism of carvedilol
- CYP2C9, 2D6, 2C19, 3A4
- Extensive 1st pass hepatic
- Metabolite is 13x more potent
ADRs of carvedilol
- Hypotension, bradycardia
- Dizzy, fatigue, weak
- Endocrine and metabolic
- Peripheral edema
What is sotalol and its uses?
- Nonselective B blocker and K blocker
- Conversion of sustained VT
- Maintenance after AF converted to NSR
- Maintenance in AF w/HCM (unlabeled)
Metabolism of sotalol
- None, excreted unchanged
- 90-100% bioavailable
- Decreased absorption w/food (take on empty stomach)
Half life of sotalol
12 hours
When must sotalol dosing be adjusted?
Renal impairment
ADRs of sotalol
- Bradycardia, CP, palpitations
- Fatigue, dizzy, weak
What is ibutilide and how is it used?
- K channel blocker
- Used acutely for AF conversion to NSR
How is ibutilide metabolized?
Extensive hepatic
ADRs of ibutilide
- Post op (Torsades)
- LV dysfunction
Ibutilide contraindications
- Long QT
- Low K
- Symptoms more than 48 hrs
What is dofetilide and its use?
- K channel blocker
- Acute conversion of AF to NSR (later for maintenance too)
What are some caveats of dofetilide?
- Less effective at higher ventricular rates
- Requires corrected QT and electrolytes prior to dosing
How does amiodarone work?
- K channel blocker
- ALSO Na, Ca channels and alpha/beta receptors
What is amiodarone used for?
- Maintain SR during AF
- Breakthrough VT/VF
- Pulseless VT/VF
ADRs of amiodarone
- Pulm toxicity
- Hypotension, HF, cardiogenic shock
- SJS
When does K channel blocking effects occur with sotalol?
Doses 160+ mg/day
Uses of Verapamil
- AVNRT, SVT, rate control in AF, HTN
- Unlabeled: migraine proph, bipolar, HCM
How is verapamil metabolized?
Extensive hepatic
ADRs of verapamil
- Gingival hyperplasia
- HA, constipation
- Fatigue, dizzy
When does verapamil dosing need to be adjusted?
End stage liver disease
Uses of diltiazem?
- PSVT and AF
- Unlabeled: stable narrow complex tachy after adenosine/vagal maneuvers
How is diltiazem metabolized?
Extensive 1st pass hepatic
ADRs of diltiazem
- Edema, AV block, brady
- HA, dizzy, SOB
How is diltiazem dose adjusted?
It is NOT adjusted with renal or hepatic disease
What is adenosine?
- Non-VW agent
- Degradation product of ATP
Uses of adenosine
- Induces rapid, reversible AV block
- Terminates SVT from AVNRT
- Allows diagnosis of pre-excitation from accessory pathways
Half life of adenosine
Less than 10 seconds
ADRs of adenosine
- Severe AV block, brady
- Bronchospasm
Contraindications of adenosine
- Symptomatic bradycardia
- 2nd/3rd AV block
- WPW
How does digoxin increase inotropy?
- Inhibits Na/K ATPase pump
- Increases Na entry, K efflux
- Increases Na/Ca exchange to increase contractility
Digoxin and maintenance of sinus rhythm
- Inconsistent
- May induce toxicity
- B blockers are safer
- BUT careful use reduces hospitalization
Metabolism of digoxin
- Minor hepatic NOT CYP dependent
- Sugar hydrolysis in stomach
- Gut bacteria
- REDUCED rate in HF
Half life of digoxin
38 hours
