Dysrhythmia Flashcards
Autorhythmic cells
Cardiac cells in the heart that create their own resting membrane potential.
Contractile cells
Cardiac cells responsible for the heart’s pumping activity.
Automaticity
Relates to heart’s ability to spontaneously generate an electrical impulse.
Depolarization
Electrical stimulation or impulse that generates an action potential.
Repolarization
Movement of membrane potential to initial resting (polarized) state.
Conduction velocity
Speed in which electrical impulse is transmitted.
Refractory period
Time-frame after depolarization where cells cannot be excited again.
Absolute refractory period
In-excitable period regardless of impulse strength
Relative refractory period
Cell is partially repolarized; Strong stimulus could cause depolarization
Vaughan-William Classification
- Class I Agents - Sodium channel blockers
- Class II Agents - beta blockers
- Class III Agents - Potassium channel blockers
- Class IV Agents - Non-dihydropyridine calcium channel blockers
Which of the Vaughan-William Classifications can cause QT prolongation?
- Class IA
- Class III
What are the agents in Class I?
- IA: Disopyramide, Quinidine, Procainamide
- IB: Lidocaine, Mexiletine, Phenytoin
- IC: Flecainide, Propafenone
What are the agents in Class II?
beta blockers
What are the agents in Class III?
- Amiodarone
- Dronedarone
- Sotalol
- Dofetilide
What are the agents in Class IV?
Non-dihydropyridine calcium channel blockers
Class I pharmacotherapy
- block Na channels (inhibit phase 0)
- C > A > B
- Delay automaticity
- Slows conduction velocity
- Varying effects on repolarization
Class I pearls
- use dependence; work better at faster heart rates
- need TDM
- can be pro-dysrhythmic
- avoid in pts with structural heart disease or CAD (linked to higher morbidity and mortality rates)
Class IA actions
- Moderate inhibition of Phase 0
- Prolongs absolute refractory period
- Prolongs repolarization
Procainamide
- Class IA
- Ventricular arrhythmias (V. tachycardia, V. fib)
- NAPA metabolite (acts like a Class III) which will cause more QT prolongation effects
- 2D6 substrate
- acute ethanol reduces serum concentraiton
- dose adjust in renal impairment (CrCl < 50 mL/min) and hepatic impairment
- TDM
Disopyramide
- Norpace®
- Class IA
- Ventricular arrhythmias
- dose adjust in renal dysfunction: CrCl < 40 mL/min and hepatic dysfunction
- Substrate of 3A4
- TDM needed
- can induce heart failure b/c it’s a negative inotrope
- anticholinergic side effects
- on Beer’s list
- administer around the clock
Quinidine
- Class IA
- Ventricular arrhythmias
- Atrial fibrillation / atrial flutter
- 3A4; eliminated by P-gp; inhibit 2D6; inhibit P-gp
- Dose adjust if CrCl < 10 mL/min
- Use with caution in hepatic impairment
- TDM
Class IA pearls
- Use has fallen out of favor due to adverse effect risk outweighing antidysrhythmic benefits
- Notorious for QT-prolonging effects
- Avoid in patients with structural heart disease and/or CAD
Disopyramide adverse effects
- Hypotension
- Exacerbate HF
- Xerostomia
- Constipation
- Urinary hesitancy
Disopyramide patient counseling
take on empty stomach
Quinidine patient counseling
- Low Na diet & food can increase rate and extent absorption
- Fruit juice & vitamin C can increase clearance of quinidine
Quinidine contraindications
- Thrombocytopenia
- 2nd or 3rd degree heart block
- Concurrent use of quinolone antibiotics that prolong QT interval
Quinidine adverse effects
- GI distress
- Diarrhea
- Dizziness
- Fatigue
- Headache
- Palpitations
- Cinchoism
Procainamide dosing
- Loading Dose: 500-600 mg IV over 25-30 minutes
- Maintenance Dose: 2-6 mg/min by continuous IV infusion
Quinidine dosing
- 267 mg of quinidine gluconate = 200 mg of quinidine sulfate
- Gluconate: ER: 648 mg PO q. 8 hours
- Sulfate: IR: 200-400 mg PO q. 6 hours ▪ ER: 300 mg PO q. 8-12 hours
Disopyramide
- Immediate release: 100-150 mg PO q. 6 hours
- Controlled release: 200-300 mg PO q. 12 hours
Procainamide adverse effects
- hypotension (decrease dose)
- heart failure
- 1st degree AV block
- lupus erythematosus-like syndrome (long term = LT)
- blood dyscrasias (long term) ex. Agranulocytosis, Bone marrow suppression, Neutropenia, Thrombocytopenia
Class IB actions
- Mild inhibition of Phase 0
- shortens absolute refractory period
- shortens repolarization
Class IB pearls
- Used for treatment of ventricular arrhythmias (because works well on contractile cells)
- Use with caution in patients with hepatic disease and HF
- Relatively higher amount of CNS-related adverse effects
- Avoid in patients with structural heart disease and/or CAD
Lidocaine
- Xylocaine®
- VF or pulseless VT
- Hemodynamic monomorphic VT
- TDM
Mexiletine
- Ventricular arrhythmias
- must take every 8 hours to decrease variation in peaks and troughs; after dysrhythmia is controlled, could change interval to Q12h
- 1A2, 2D6 substrate
- Caution in patients with hepatic impairment and/or HF
Lidocaine doses
- 1 - 1.5 mg/kg bolus
- for VF or pulseless VT: 0.5 to 0.75 mg/kg bolus every 5 to 10 minutes (maximum cumulative dose: 3 mg/kg)
- Continuous infusion: 1 - 4 mg/minute
- Use lower dose in patients with hepatic dysfunction (metabolized by liver)
- 1A2, 3A4 substrate
Mexiletine doses
- 200-300 mg PO q. 8 hours
- MDD of 1.2 grams
Lidocaine contraindications
- Premixed injection may contain corn-derived dextrose and its use is contraindicated in patients with allergy to corn or corn-related products
- Severe degrees of SA or AV block (except in patients with a functioning artificial pacemaker)
Mexiletine adverse effects
- GI effects limits people from tolerating this drug
- Gi: GI distress, N/V
- Dizziness
- Ataxia
- Hepatotoxicity
- Blood dyscrasias
- DRESS
Mexiletine patient counseling
- Take with food
- Avoid diets or medications that increase urinary pH
Mexiletine patient counseling
- Take with food
- Avoid diets or medications that increase urinary pH
- do not recommend taking with antacid b/c if you make the urine basic, it doesn’t allow medicine to be secreted in renal tubule
Class IC actions
- Major inhibition of Phase 0
- Minimal effect on absolute refractory period
- Minimal prolongation of repolarization
Class IC actions
- Major inhibition of Phase 0
- Minimal effect on absolute refractory period
- Minimal prolongation of repolarization
Class IC pearls
- Used primarily for supraventricular tachycardia
- Commonly prescribed in the outpatient setting
- Both agents have dietary considerations that effect plasma levels
- TDM is not commonly performed in practice
- Avoid in patients with structural heart disease and/or CAD
- used for Paroxysmal atrial fibrillation and Paroxysmal supraventricular tachycardia
Flecainide
- Tombocor®
- 2D6 substrate
- Caution in patients with hepatic dysfunction
- Dose adjust in patients with CrCl < 35 mL/min
Propafenone
- Rythmol®
- monitor CBC, LFT’s, ECG
- Use with caution in patients receiving beta-blockers (b/c has BB activity)
- 2D6 substrate
- inhibits P-gp
- Dose adjust in hepatic dysfunction
Flecainide doses
- 50-100 mg PO q. 12 hours
- MDD: 300-400 mg
Propafenone doses
- ER capsule: Initial 225 mg PO every 12 hours; May increase up to maximum of 425 mg every 12 hours
- IR tablet: Initial 150 mg PO every 8 hours; May increase up to maximum of 300 mg every 8 hours
Flecainide contraindications
- Ritonavir
- Pre-existing 2nd or 3rd degree AV block
Flecainide counseling
- Clearance may be decreased in patients following strict vegetarian (via increase in urine pH)
- Milk may interfere with the absorption of flecainide
Flecainide adverse effects
- Dizziness
- Headache
- Fatigue
- Nausea
- Visual disturbances
- Dyspnea
Propafenone counseling
avoid grapefruit juice
Propafenone counseling
avoid grapefruit juice
Propafenone adverse effects
- Unusual taste
- Nausea
- Vomiting
- Dizziness
- Fatigue
- Blurred vision
Class II action
- Inhibit sympathetic influences on electrical activity
- Decrease SA/AV node automaticity & conduction velocity
- Increase action potential duration and effective refractory period
What are the beta blockers available for dysarrhythmia?
- Beta-adrenergic receptor antagonists with MSA: Propranolol, Metoprolol
- Beta-blockers without MSA are still commonly used in practice: Esmolol
Propranolol
- Inderal®
- Non-selective beta-blocker
- Can be used to treat arrhythmias caused by hyperthyroidism
- metabolized by 1A2, 2D6
Propranolol dosing
- 30-320 mg/day, divided every six to eight hours, orally (MDD of 640 mg)
- Can transition to extended-release formulation when dysrhythmia is controlled
Propranolol counseling
- Ethanol may increase or decrease plasma levels of propranolol
- High-protein diet can increase bioavailability
Esmolol
- Brevibloc®
- Advantageous when patients possess tenuous blood pressure/heart rate
- Metabolized by blood cell esterases.
- When transitioning to oral beta-blocker therapy, infusion should be reduced by 50% thirty minutes following the first dose of the alternative agent
Esmolol doses
- Continuous infusion
- 500 mcg/kg/minute over 1 minute, then 50 mcg/kg/minute (max of 200 mcg/kg/minute)
Class III
- K channel blockers
- prolong repol -> prolong QT interval
Which drugs are in the Class III?
- Amiodarone (Pacerone®, Cordarone®)
- Dronedarone (Multaq®)
- Ibutilide (Corvert®)
- Dofetilide (Tikosyn®)
- Sotalol (Betapace®, Betapace AF®)
Dronedarone brand name
Multaq®
Ibutilide brand name
Corvert®
Amiodarone
- Blocks all four Vaughan-Williams classifications (protects itself from having QT prolongation)
- Used to treat both atrial and ventricular arrhythmias
- metabolized by 2C8, 3A4
- inhibit P-gp, 2C9, 3A4
Amiodarone dose
- Oral: 200-1600 mg/day
- IV: 150-300 mg rapid bolus, then 1 mg/minute for 6 hours, then 0.5 mg/min for 18 hours
Amiodarone adverse effects
- hypotension
- bradycardia
- thyroid dysfunction (hyper- and hypo-)
- N/V
- Acute and chronic liver impairment
- Skin photosensitivity
- Pulmonary toxicity: Pneumonitis, Fibrosis
- Peripheral neuropathy
- Optic neuritis
Amiodarone counseling
Avoid grapefruit juice
Amiodarone contraindications
- Hypersensitivity to iodine
- Second and third-degree AV block
- Cardiogenic shock
Sotalol
- Used to treat atrial and ventricular dysrhythmias
- as you increase the dose, you get more anti-arrhythmic effects
- Possesses predominantly non-selective beta-blocking properties at lower doses
- Get baseline QTc interval prior to initiation
- Frequency adjust in patients with CrCl ≤60 mL/min
- Can cause life threatening ventricular tachycardia associated with QT interval prolongation
- when dose started or changed, must be admitted to hospital for monitoring
Sotalol dosing
- Oral
- 80-160 mg twice daily
Sotalol adverse effects
- Bradycardia
- Fatigue
- Dizziness
- Weakness
- Dyspnea
- Prolongation of QT-interval
Sotalol contraindications
Contraindicated if CrCl < 40 mL/min
Dofetilide
- Tikosyn
- Used to treat atrial fibrillation and atrial flutter
- Measure QTc before initiation
- Safe to use in patients with CAD or structural heart disease.
- Dose adjust in patients with CrCl < 60 mL/min
Dofetilide dosing
- Oral
- 125-250 micrograms twice daily
Dofetilide adverse effects
- Headache
- Dizziness
- QT-prolongation
Dofetilide contraindications
- cimetidine
- dolutegravir
- hydrochlorothiazide
- itraconazole
- ketoconazole
- megestrol
- prochlorperazine
- trimethoprim
- verapamil
Class iV
- Non-Dihydropyridine Calcium Channel Antagonists
- Treat supraventricular dysrhythmias
- Atrial fibrillation/flutter
- Paroxysmal supraventricular tachycardia
Verapamil
- Calan®
- substrate of 3A4 and P-gp
- Moderate inhibitor of 3A4
- Inhibitor of P-gp
- May need to dose adjust in hepatic/renal impairment
- more GI effects compared to Diltiazem
Verapamil dosing
- IV
▪ 0.075 – 0.15 mg/kg bolus over 2 minutes
▪ 5 mg/hour CI - Oral
▪ 240-480 mg daily in divided doses (three times daily), initially
▪ Transition to extended-release formulation
Diltiazem
- Dilacor®, Cardizem®
- substrate of 3A4 and P-gp
- Moderate inhibitor of 3A4
- Dose adjust in patients with liver impairment
Diltiazem dosing
- IV ▪ 0.25 mg/kg IV bolus over 2 minutes ▪ 5-10 mg/hour CI ▪ Avoid exceeding 15 mg/hour - Oral ▪ Initially 30 mg q. 6 hours ▪ 120-360 mg/day in divided doses or extended-release formulation
