lecture 19 Flashcards
Lidocaine / Mexiletine
Class IB anti-arrhythmic
slow phase 0 and decrease the slope of phase 4
shorten phase 3
Little effect on depolarization phase of action
potential in normal cells
Rapidly associate and dissociate with Na+ channels
block the Na channels
Small increase in QRS. Clinically insignificant
decrease in QT
MOA of lidocaine
Class IB
local anesthetic
useful for ventricular arrhythmias
little effect on the K channels
CA of lidocaine
Acute treatment of ventricular arrhythmias from
myocardial infarction or cardiac manipulation
Treatment of digitalis-induced arrhythmias
little effect on atrial arrhythmia
AE of lidocaine
CNS effects (drowsiness, slurred speech, agitation etc.)
• Little impairment of left ventricular function
• NO negative inotropic effect
• Cardiac arrhythmias (<10%)
• Toxic doses: convulsions, coma
Mexiletine
Class IB
Management of severe ventricular arrhythmias
AE: CNS and GI
Flecainide / Propafenone
Class IC drugs
depress of phase 0 of AP
slowing of conduction
no change in repolarization
marked Na channel block
Significant increase in QRS
CA of flecainide
Severe symptomatic ventricular arrhythmias,
premature ventricular contraction or ventricular
tachycardia resistant
Severe symptomatic supraventricular arrhythmias &
prevention of paroxysmal atrial fibrillation
AE of flecainide
- Negative inotropic efffect (aggravates CHF)
- CNS effects: dizziness, blurred vision, headache
- GI effects: nausea, vomiting, diarrhea
- Life-threatening arrhythmias & ventricular tachycardia
Propafenone CA
Used for treatment of life-threatening ventricular
arrhythmias and the maintenance of normal sinus
rhythm in patients with symptomatic atrial fibrillation
AE of propafenone
Also has b-blocking activity therefore bronchospasm, aggravation of underlying heart failure
similar to flecainide
Quinidine, procainamide, disopyramide
Class IA
Block both Na+ and K+ channels
Increase both QRS and QT
beta blockers as anti-arrhythmic drugs
reduce HR and contractility
slow conduction of impulses
reduce rate of depolarization
prolonged repolarization at AV node
CA of beta blockers (metro and prop)
Reduce incidence of sudden arrhythmic death after MI
Control of supraventricular tachycardias (atrial
fibrillation & flutter, AV nodal re-entrant tachycardias)
Ventricular tachycardias
esmolol as anti-arrhythmic
treatment of acute arrhythmias occurring during surgery or in emergency situations
AE of the Class II drugs
Bradycardia, hypotension, CNS effects etc.
Contraindicated in acute CHF, severe bradycardia or
heart block and severe hyperactive airway disease
Class III anti-arrhythmic
block of the repolarizing K channels
prolonged repolarization
Amiodarone MOA
similar to thyroxine
shows MOA of multiple classes of drugs for arrhythmia
most prominent is K channel blockade
CA of amiodarone
commonly used
Used in the management of ventricular &
supraventricular arrhythmias
the drug of choice for acute VT refractory to cardioversion shock
AE of amiodarone
interstitial pulmonary fibrosis, GI intolerance, tremor,
ataxia, dizziness, hyper- or hypothyroidism, liver
toxicity, photosensitivity, neuropathy, muscle weakness,
hypotension, bradycardia, AV block, arrhythmias
contraindications of amiodarone
- Patients taking:
- Digoxin, theophylline, warfarin, quinidine
Patients with: • Bradycardia • SA or AV block • Severe hypotension • Severe respiratory failure
Sotalol MOA
- Potent non-selective b-blocker
- Inhibits rapid outward K+ current
- Prolongs repolarization & duration of action potential
- Lengthens refractory period
CA of sotalol
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
AE of sotalol
Lowest rate (of antiarrhythmics) of acute or long-term
adverse effects
Torsades de pointes (prolongs QT interval)
Use with caution in patients with renal impairment
similar AE as other beta blockers
Dofetilide
potent and pure K channel inhibitor
CA:
Conversion of atrial fibrillation / flutter to normal
sinus rhythm
AE of dofetilide
- Headache, chest pain, dizziness, ventricular tachycardia
* Torsade de Pointes (prolongs QT interval)
Class IV anti-arrhythmics
Ca channel blockers
slow rise in the AP
verapamil and diltiazem
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
effects:
Decrease contractility (negative inotropy)
Decrease heart rate (negative chronotropy)
Decrease conduction velocity (negative dromotropy)
MOA of verapamil and diltiazem
Slow conduction & prolong effective refractory period
inhibits the Ca channels
CA of verapamil and diltiazem
• More effective against atrial than ventricular arrhythmias
• Supraventricular tachycardia is major arrhythmia
indication
• Reduction of ventricular rate in atrial fibrillation &
flutter
• Hypertension, angina
AE of verapamil and diltiazem
- Negative inotropes
- Transient decrease in BP
- CNS effects (headache, fatigue, dizziness)
- GI effects (constipation, nausea)
contra:
increase the concentrations of other cardiovascular drugs such as digoxin, dofetilide, simvastatin, & lovastatin
digoxin and arrhythmia
• Shortens refractory period in atrial & ventricular
myocardial cells
• Prolongs effective refractory period & diminishes
conduction velocity in AV node
Control of ventricular response rate in atrial
fibrillation & flutter with impaired left ventricular
function or heart failure
MOA of digoxin in arrhythmia
• Direct AV node blocking effects & vagomimetic
properties:
• Inhibition of Ca2+ currents in AV node
• Activation of Ach-mediated K+ currents in atrium
hyperpolarization
shorten atrial AP
increase AV node refract
adenosine and arrhythmia
High doses = decreases conduction velocity & prolongs refractory period as well as decreasing automaticity in AV node
MOA of adenosine
- Enhances K+ conductance
- Inhibits cAMP-mediated Ca2+ influx
- Leads to hyperpolarization esp. in AV node
CA of adenosine
drug of choice for abolishing acute supraventricular tachycardia
AE of adenosine
• Flushing • Burning • Chest pain • Hypotension • Bronchoconstriction in asthmatics (may persist up to 30 min)
magnesium
Functional Ca2+ antagonist
uses:
• Torsades de pointes
• Digitalis-induced arrhythmia
• Prophylaxis of arrhythmia in acute MI
atropine and arrhythmia
Used in bradyarrhythmias to decrease vagal tone
