Antiarrhythmic drugs Flashcards
What are the prototypes of Class III drug
Amiodarone, Sotalol, Dofetilide
Pharmacokinetics of amiodarone
extensively tissue bound, long half life up to 100 days
MOA of Amiodarone
K+ , Na+, Ca++ channel blockade, alpha and beta adrenergic blockade, Jack of all trades
Adverse effects of amiodarone
concentrates in tissues, yellow brown corneal microdeposits, photosensitivity, blue-gray skin
Gastrointestinal, constipation, loss of appetite, nausea, vomiting
Neurological, neuropathy, fatigue, motor
hypotension due to ca++ effects
Life threatening pulmonary toxicity (10-15%)
Hepatotoxicity
Thyroid dysfunctions
Drug interactions for amiodarone
increases plasma levels of many antiarrhythmia drugs
amiodarone plus beta blockers of Ca2+ chanel antagonists can cause sinus arrest or AV block, worsen congestive heart failure
long lasting interaction possibility
Summary of amiodarone
highly effective due to many targets, also has many adverse effects for the same reason
Sotalol MOA
L-isomer is beta adrenergic receptor blocker
D-isomer is a K+ channel blocker
Therapeutic use of Sotalol
atrial flutter and fibrillation, ventricular tachyarrhythmias
Adverse effects of Sotalol
Torsades de pointes
Beta blocker effects
MOA of Dofetilide
Selective blocker of CARDIAC K+ channels
Adverse effects of Dofetilide
Torsades de pointes (2%)
few extracardiac effects
Therapeutic use of dofetilide
typically only used in hospital settings with specially trained physicians due to high risk of torsades de pointes
Class IV anti-arrhythmia drugs
verapamil and diltiazem
MOA of verapamil and diltiazem
Blocks Ca+ channels, direct action on SA nodal cells generally slows heart rate
Therapeutic use of verapamil and diltiazem
first choice with adenosine for supraventricular tachycardia due to AV nodal reentry
reduce ventricular rate in atrial flutter
Adverse effects of verapamil and diltiazem
Cardiac, ventricular fibrillation and hypotension, AV block, decreased contractillity
Extracardiac, constipation, peripheral edema, CNS effects
Drug interactions with verapamil and diltiazem
Bradycardia or AV block when administered with beta blockers or digoxin
Pharmacokinetics of verapamil
short half live, can be removed from body quickly
Non-classified drugs
Adenosine
Adenosine MOA
Activates adenosine receptors, activates K+ channels which hyperpolarizes AV nodal tissue
Therapeutic use of adenosine
IV bolus terminates paroxysmal supraventricular tachycardia, can even cause complete cardiac block. Very short time of action (sec) makes it safer than verapamil
Effect of antiarrhythmic drugs on ECG
P-R interval prolonged by CA++ channel blockers
QRS complex is prolonged by Na+ channel blockers
QT interval is prolonged by K+ channels
Do atrial or ventricular fast tissues have a longer plateau
ventricular
What are the slow tissues and how are they different from the fast tissues
SA and AV nodes. They do not have sodium channels. Instead they have voltage activated calcium channels
What is a common consequence of K+ channel blockers
Early after-depolarization (Torsades des pointes)
What is the common cause of delayed after-depolarization
digoxin through Ca+ overload
What is a common cause of ectopic pacemaker arrhythmias
ischemia due to dysfunction of the loss of Na+/K+ ATPase
How do you treat a reentry arrhythmia
lengthen the effective refractory period (ERP) by inhibiting K+ channels
What is PR interval
the time for the impulse to pass through AV node
What is the QT interval
length of ventricular action potential
What is the definition of Tachycardia
Rapid beating of atria or ventricles (100-200 bpm)
What causes tachycardia
reentry arrhythmia or ectopic pacemaker
Supraventricular tachycardias can be caused by…
AV nodal reentry
Wolff-Parkinsons-White syndrome due to bundle of Kent
What are paroxysmal tachycardias
rapid abnormal beats with sudden onset and offset
How is a flutter defined
rapid regular contractions 200-350 bpm that are self sustaining. Usually due to reentry. Can degenerate into fibrillation
Which type of fibrillation is lethal
ventricular
MOA of Class 1a drugs
block both K+ and Na+ channels
Prototype Class 1a drugs
Quinidine and procainamide
Therapeutic use of class 1a drugs
beneficial for arrhythmias of fast tissue.
Quinidine side effects
cardiac: Torsade de pointes
extracardiac: GI, tinnitus,
dizziness, blurred vision and headaches at hich doses
Rare: thrombocytopenia, hepatitis, angioedema, fever
General pharmacokinetic profile of antiarrhythmics
metabolized in liver and/or kidney, plasma bound, half life of hours
Therapeutic use of quinidine
not first line due to side effects, supraventircular arrhythmias and ventricular tachycardia
Metabolism of procainamide
metabolized to NAPA in liver, excreted in kidney
slow and fast acetylators
Side effects of procainamide
Cardiac: torsade de pointes less common than with quinidine, but increased in fast acetylators
hypotension
Extracardiac: Lupus, nausea, diarrhea, hepatitis, rash, fever, agranulocytosis
Theapeutic use of procainamide
atrial and ventricular arrhythmias, not for long term therapy due to lupus.
Class 1b drugs
Na+ channel block, lidocaine
Moa of lidocaine
use-dependent blockade of Na+ channels
Pharmacokinetics of lidocaine
first pass metabolism in liver, IV or IM
half life 1-2 hrs
Side effects of lidocaine
fewer cardiac side effects that 1a or 1c
CNS: parasthesis, drowsiness, tinnitus, blurred vision
Toxic: tremors, convulsions, hearing disturvances, unconsiousness, respiratory arrest
Therapeutic use of lidocaine
suppressing ventricular tachycardias and arrhythmias in depolarized tissue
Class 1c MOA
block of healthy Na+ channels
Class 1c prototype
flecainide
Therapeutic use of flecainide
supraventricular arrhythmias in patients with otherwise normal hearts
Side effects of flecainide
significantly proarrhythmic, prolonged use decreases survival
Class II MOA
block calcium channels by blocking beta-adrenergic receptor stimulation
Class II prototype
propranalol
Cardiac action of propranalol
negative ionotropic and chronotropic effect. Decreases excitability and slows conduction velocity.
Therapeutic use of propranalol
ventricular arrhythmias due to exercise or emotion, after MI to prevent recurrent infarction. long-term survival benefit. Supraventricular arrhythmias
Side effects of propranalol
SA and AV block, withdrawl symptoms, dyspnea
