Anti-arrhythmias Flashcards
Fast Response
Atrial & Ventricular muscle His-Purkinje fibers
drugs that affect this AP block Na+ or K+ channels
QRS and QT
intervals
Na, Ca, K
Slow Response
SA and AV node SANS via NE and PANS via ACh affect this AP Ca, K
DADs & EADs
Under some pathophysiological conditions, a normal cardiac
action potential may be interrupted or followed by an abnormal
depolarization. If this abnormal depolarization reaches threshold it may give rise to secondary upstrokes that can propagate and create abnormal rhythms. These abnormal secondary upstrokes occur only after an initial normal upstroke and thus are referred to as triggered rhythms. There are two forms of triggered rhythms: late or delayed afterdepolarizations (DADs) and early afterdepoalrizations (EADs).
DADs info
DADs arise out of phase 4 of the action potential whereas EADs
arise out of phase 3. DADs are associated with calcium overload
which can occur with excess sympathetic activity, digoxin, or
myocardial ischemia. They are more likely to occur at fast heart
rates. EADs are exacerbated at slow heart rates, when
extracellular potassium is low, and with drugs that prolong
repolarization. When repolarization is markedly prolonged,
polymorphic ventricular tachycardia with a long QT interval,
known as torsade de pointes, may occur. Torsades triggers
functional re-entry. Individuals with congenital long QT
syndrome are genetically predisposed to torsades because they
have mutations in either sodium or potassium channel genes.
RE-ENTRY
Normally, impulses from higher pacemaker centers are
conducted down pathways that bifurcate to activate the
entire ventricular surface. A phenomenon called reentry
(also known as “circus movement”) can occur if one
impulse reenters and excites areas of the heart more than
once. The path of the reentering impulse may be confined
to a very small area such as within or near the AV node, or
it may involve large portions of the atrial or ventricular
walls
Wolff-Parkinson-White syndrome is a reentry
arrhythmia
there may be arrhythmias with multiple reentry circuits
which can cause extra beats or a sustained tachycardia
Re-entry conditions
In order for reentry to occur, three conditions must
coexist: 1) there must be an obstacle to conduction,
2) there must be unidirectional block at some point in the
circuit, and 3) conduction time around the circuit must be
long enough so that the retrograde impulse does not enter
refractory tissue as it travels around the obstacle, i.e.,
conduction time must exceed the effective refractory
period.
CLASS I ANTIARRHYTHMICS
- Block voltage sensitive Na+ channels which are
responsible for rapid influx of Na+ in phase 0 - Selectively blocks high frequency excitation that occurs
in arrhythmias without preventing normal frequency heart
Beat - Sodium channels: resting, open, inactivated
- Bind sodium channel with greatest affinity in the open or inactivated state
Class Ia drugs
a. dissociate at an intermediate rate (1-10 sec)
b. moderate depression of phase 0 (Na+ block) and prolongs
repolarization and increases the ERP (K+ block)
Class Ib drugs
a. dissociate rapidly (
Class Ic drugs
a. associate and dissociate the slowest (>10 sec)
b. drugs potently suppress phase 0 and slow conduction rate
c. minimal effects on repolarization and refractory period
Ia
Quinidine
Procainamide
Disopyramide
Quinidine
a. is the prototype (oldest) Class Ia drug; optical
isomer of quinine (antimalarial); less frequently used
due to newer drugs; extracted from the cinchona plant
b. actions: antimalarial, antimuscarinic (inc HR), a1
blocker (hypotension)
c. cardiac effects: acts directly to block sodium
channels (~ 3 sec) and potassium channels; can cause
widening of PR, QRS and QT intervals; both
antimuscarinic actions and α1 blocking effects can
HR (PR interval) and precipitate atrial flutter or
fibrillation (proarrhythmic)
Quinidine 2
d. sodium channel blockade: increased threshold for
excitability, decreased automaticity
e. potassium channel blockade: prolongs action
potential in most cardiac cells; elicits EADs at slow
heart rates
f. therapeutic use: maintenance of sinus rhythm in
patients with atrial flutter or fibrillation and in the
prevention of recurrence of ventricular tachycardia
or ventricular fibrillation
quinidine adverse
cinchonism (vertigo, tinnitus,
headache, fever), diarrhea (30-50% of patients) which
may induce hypokalemia and potentiate torsades de
pointes (which occurs in 2-8% of patients; may occur
at therapeutic levels)
Procainamide
a. actions: similar to quinidine in both sodium and potassium channel block; is a derivative of the local anesthetic procaine; lacks the antimuscarinic and alpha-1 blocking effects of quinidine
b. therapeutic uses: use only in life-threatening arrhythmias; may be better for ventricular arrhythmias; used for WPW
Procainamide kinetics & adverse
pharmacokinetics: oral (short t ½ means dosing 3-8 times a day), IV; a portion of the drug is acetylated in the liver to N-acetylprocainamide (NAPA); this metabolite lacks sodium channel blocking ability but blocks potassium channels (prolongs the duration of the action potential)
adverse effects: can get torsade de pointes with elevated levels of NAPA (prolonged QT); with chronic use can get a lupus-like syndrome in 25-30% of patients (positive ANA); hypotension
