A-21. Antiarrhythmic agents. Flashcards
Class I/A antiarrhythmic MOA and drugs
Na+ channel inhibitors; intermediate dissociation and K+ channel inhibition
a. ) quinidine
b. ) disopyramide
c. ) procainamide
Class I/B MOA and drugs
Na+ channel inhibitors; fast dissociation
a. ) lidocaine
b. ) mexiletine
c. ) phenytoin
Phase 0, depolarization/upstoke phase in cardiac action potentials
Sodium influx
Phase 1, notch of cardiac action potential
slight repolarization as sodium channels inactivate
Phase 2, plateau of cardiac action potential
Ca2+ influx
Phase 3, repolarization of cardiac action potential
K+ efflux
phase 4, pacemaker current
K+ influx
Absolute refractory period
h gate (fast gate) closes, leaving the channel in an inactive conformation
Relative refractory period
As cell repolarizes h gate open again until sufficient depolarization triggers another AP
Class 1 antiarrhythmics bind Na+ channels in which conformation? And which confirmation does it not bind?
Class I antiarrhythmics bind Na+ channels in active and inactive conformations, but not in the resting state
Types of calcium channels in cardiac myocytes? Which type are responsible for plateau phase of cardiac action potential? Which two antiarrhythmics target this channel type?
L and T-type calcium channels.
L-type channels are responsible for plateau phase.
Verapamil and diltiazem inhibit these L-type calcium channels.
Which class of antiarrhythmics prolong repolarization? What are they good for treating? What risks does it cause?
Class III is a good class of antiarrhythmic for prolonging repolarization. They are good at treating re-entry arrhythmias by prolonging the refractory period. TdP tachycardia risk is increased.
Two types of arrhythmias groupings
Impulse formation or impulse conduction abnormalities
Impulse formation can be separated into?
Regular- only the rate is modified, as in tachy- or bradycardia
Irregular- as in triggered impulse formation abnormailites such as…
a.)Early After depolarization (EAD)
b.)Delayed After depolarization (DAD)
Early after depolarization is
ion channel (Ca or Na) reactivate before repolarization has finished, triggering an extrasystole before the cell can fully repolarize. Often the trigger of TdP tachycardia and can be caused by anything which prolongs QT interval (hypokalemia, drugs, or genetic abnormalities)
Delayed after depolarization is
After repolarization is complete, an increased IC calcium level activates the Na/Ca exchanger
Such as triggering an extrasystole, due to cardiac glycoside
Impulse conduction abnormality can be due to
re-entry mechanism which requires
1.) parallel pathway
2.) a unidirectional block
3.) a short enough refractory period in the ublocked path
An AP travels along the unblocked pathway, then travels retrograde back through the unidirectionally block path, restimulating the unblocked path after it’s refractory period, resulting in an extrasystole
Re-entry arrhythmias can be treated by prolonging refractory periods of cardiac myocytes with drugs that …
block K+ channels (thus slowing repolarization) or blocks Na+ channels (thus leaving them inactive)
Class I antiarrhythmic dependence effect? What does this mean?
Use-dependence/state-dependence
Effect depends on heart frequency will inhibit a tachycardia HR, but have less effect on normal HR.
Since class I antiarrhythmics bind inactive and active, not the resting conformation. The more rapid the heart rate the more likely it will be in active state.
IC, IB, IA
Order from most to least use-dependence
IC>IA>IB
Class 1 antiarrythmics do what to the slope of depol, conduction, and QRS?
How did it effect SA/AV nodes
It decreases the slope of depolarization (phase 0), slows conduction, and widens QRS
Na+ channel blockers do not affect depolarization in the SA/AV nodes
Class I/A antiarrythmics kinetics
intermediate dissociation (this plus the anticholinergic effects, tends to slow physiological HR leading to bradycardia) intermediate affinity inhibit K channels and prolongs AP (increases risk of TdP)
The two Class I/A antiarrhythmic drugs not used anymore
ajmaline (parenteral)
prajmaline (oral)
both quinidine analogs
Quinidine
Indication?
Kinetics?
Side effects?
Indication: both atrial and ventricular tachyarrhythmias
Kinetics: oral admin; medium DOA
Side Effects
1.) Inhibits alpha receptors increasing reflex tachycardia
2.) Anticholinergic effect increases HR and AV conduction which can increase rate of ventricle
3.) At low doses anticholinergic effect dominates/ High doses Na+ channel blockade dominates
-Often combind with something to slow AV conduction (BB or verapamil/diltiazem)
-Note; digoxin also decreases HR and conduction, but quinidine causes an increased serum digoxin level, so the two drugs can’t be combined
4.) Negative inotropic effect- careful with admin in heart failure
5.) Chinchonism- tinnitus, headache, and dizziness
6.) Thrombocytopenia- rare
Procainamide
How does it compare to to Quinidine?
Side effects?
Less anticholinergic and less negative inotropic effect, rarely used now due to side effects.
Side effects are similar to quinidien plus
Lupus-like syndrome-via long term treatment (athralgia/-itis, pericarditis, pulmonitis, etc.)
