Pharm Anti-arrhythmic drugs

Treatment options for arrhythmias
devices (pacemaker/defibrillator), surgery, drugs
Needed for reentry
unidirectional block, retrograde conduction, conduction time>ERP
Drugs abolish reentry by
slowing AP conduction so that retrograde impulses meet refractory tissue
Drugs exhibiting use dependence (anti-arrhythmics)
Na channel blockers, Ca channel blockers
K+ channel blockade molecular changes
Prolongs repolarization, increases ERP, slows AP conduction, stops reentry
Class I antiarrhythmics: target
Na channel blockers
Class IA antiarrhythmics: target
Na and K channel blockers
Class I antiarrhythmics: pharm effects
Use dependence, slowed AP conduction abolishes reentry, block of diastolic current suppresses ectopic pacemakers
Class I antiarrhythmics: uses
atrial reentrant arrythmias, ventricular reentrant arrythmias. Use is decreasing because of toxicity
Class I antiarrhythmics: types
procainamide (IA), lidocaine (IB), flecainide (IC)
Class I antiarrhythmics: adverse effects
CNS (headache, dizziness, tinnitus), torsade de pointes, ventricular arrythmias, myocardial depression, muscarinic blockade->enhanced AV conduction, a-adrenergic blockade->hypotension, lupus-like syndrome (procainamide). High K+ enhances the toxicity of Na channel blockers because it produces partial membrane depolarization–>more channels in the inactivated state.
Class II antiarrhythmics: types
Propranolol, metopronol, Esmolol, acebutolol
Class II antiarrhythmics: useful effects
block of catecholamine induced cardiac effects, suppression of ectopic pacemakers, slowed AV conduction
Class II antiarrhythmics: uses
catecholamine induced arrhythmias, slowing ventricular rate during atrial tachycardias, post MI suppression of ectopic pacemakers
Class III antiarrhythmics: types
sotolol, Ibutilide
Class III antiarrhythmics: target
K+ channels
Class III antiarrhythmics: adverse effects
reverse use dependence, torsade de pointes, B-block (sotolol)->heart block, bronchospasm, hyptension
Class III antiarrhythmics: uses
arrhythmias that are refractory to other safer drugs
Class IV drugs: types
verapamil (Ca channel blocker)
Class IV drugs: mechanism
blockade of Ca channels in the SA and AV node
Class IV drugs: ECG
prolonged PR interval
Class IV drugs: pharm effects
Abolishes reentry in Ca dependent cells, suppresses ectopic pacemakers if due to Ca
Class IV drugs: adverse effects
myocardial depression, CHF, SA and AV node depression (symptomatic bradycardia)
Class IV drugs: uses
AV nodal reentry tachycardia, slowing the ventricular rate in atrial flutter or fib
Adenosine: target
purinergic receptors, type I
Adenosine: useful effects
increases outward K+ to hyperpolarize the membrane, decreases inward Ca current
Adenosine: ECG
prolonged PR
Adenosine: adverse effects
flushing, hypotension
Adenosine: PK
administer as a bolus
Adenosine: uses
AV nodal rentry tachycardia
Amiodarone: target
K, Na, Ca channels and b-receptors
Amiodarone: ECG
prolonged QT, PR, QRS
Amiodarone: pharm effects
slowed conduction abolishes reentry, reduced inward diastolic current decreases ectopic automaticity
Amiodarone: adverse effects
bradycardia, myocardial depression, CHF, pulmonary fibrosis, hepatocellular necrosis, neurological effects, thyroid dysfunction, microcrystalline deposits in the skin and cornea
Amiodarone: pk
5-10 day half life, metabolized by CYP3A4
Amiodarone: uses
arrhythmias resistant to other drugs, VT/VF, other arrhthmias