antiarrhythmics 63/64 Flashcards
Quinidine
Class 1A
inhibits Na+ channels but also K+ channels
used for variety of arrhythmias, but limited by SEs
increased used for vfib, Brugada syndrome (inherited ion channelopathy–>vfib): can also be stopped with cardioversion, and afib in short-QT syndrome
past: used to keep cardioverted a fib pts in the cardioverted state
Procainamide
Class 1A
quite similar to quinidine except K+ channels are inhibited by an *acetylated hepatic metabolite (NAPA)
only IV use
Lidocaine
Class 1B
rapidly interact with phase 0 Na channels, shortens phase 3 depolarization, dec. AP duration and ERP
inhibition of small population of late opening sodium channels still open during the AP plateau (opened more by ischemic conditions)
emergent ventricular arrhythmias, during MI
decrease slope phase 4
abolishes ventricular reentry
stops TdP because decreases AP duration
IV only (1st past effect: dec. action and increases toxic metabolites)
MOA: not always logical, can stop reentry via decreasing AP duration?
stop torsades by reducing EAD
Flecainide
Class 1C
reserved for severe cases resistant to other drugs for (FA: SVTs, including afib; only last resort in refractory VT)
block phase 0 Na+ the most, markedly suppresses phase 0 slope, slows conduction
inhibits some K+ channels, but no net effect as it blocks late Na+ channels as well
increases threshold for phase 0 and decrease slope of phase 4 (both reduce abnormal automaticity)
Propranolol
Class II
non-selective (B1, B2-block)
reduces adrenergic-driven arrhythmic death after MI
membrane stabilization at unacceptably high doses-not used this way
Acebutolol
Class II
B1-selectivity, less bronchospasm
partial agonist activity (ISA) may decrease risk of too much suppression of normal cardiac function
Esmolol
Class II
short duration of action (only IV)
acute arrhythmias during emergent situations, surgery
Amiodarone
Class III: block K+ channels
actions similar to I, II and IV, decrease cell-to-cell coupling, slows functional movement of AP, slows velocity of AP
severe and refractory (resistant) SVT and Vtach, combined with auto ICD (reduces how often shock must deliver shocks: “reduced tachyarrhythmic burden”)
severely limited by SEs
FA: afib, aflutter, vtach
fast IV, slow oral
may be used emergently when lidocaine not recommended
Dofetilide
Class III
inhibits only K+ channels (mimics NAPA) prolongs phase 3, no multiple mechanisms like amiodarone
mostly for SVTs, i.e. afib
corrects reentry phenomenon
Verapamil
Class IV
Diltiazem
Class IV
Adenosine
miscellaneous (not a class)
synthetic form, IV
used to tx emergent arrhythmias, short duration
stops acute PSVTs (paroxysmal) (due to WPW or AV nodal origin)
very short duration of action (less than 15s)
decreases conduction and abnormal AP formation in AV node by dec. Ca2+ influx and increasing ACh-sensitive phase 4 K+ current (hyper polarizing resting potential)
also prolongs AV node refractory period
Class I antiarrhythmics block
Na+ channels
Class II antiarrhythmics block..
Ca2+ channels
Class III antiarrhythmics block
K+ channels
APs occur in phases
Phase 0: upstroke: fast depolarization -85mV to 0mV
Phase 1: early-fast repolarization (we ignored this)
Phase 2: important plateau phase (drugs affect here)
Phase 3: repolarization phase back to resting
Phase 4: in between phase (resting, diastole)
AP phases travel from place to place in heart
start in SA node
also change shape based on location
threshold for phase 0
need something to get it to threshold, will get up the rest on on
some tissues can do this on own, i.e. SA node, AV node, purkinje: have automaticity
steepest slope, reaches AP 1st–>atria–>AV node–>Purkinje fibers–>rest of heart
before these tissues reach threshold on their own
when these other tissues reach threshold on own: pathological
channels for phase 0
1st reach threshold
then Na+ enters cell (also Ca2+) neutralize the internal negative charge: upstroke: goes from -85 mV to 0mV
very steep, much Na+ coming in
some Na+ channels may remain open, esp. during ischemia: late Na+ channels
Phase 1 channels
some K+ outflux, we mostly ignore
Phase 2 channes
Ca2+ comes in, keeps above 0 mV
then close! and K+ channels open, K+ flows out, some downward movement
Phase 3
more K+ flowing out, back down to resting potential
Phase 4
refractory to AP from phase 0-beginning phase 4
only digoxin acts here
leakage of Na+ and Ca2+ in, K+ out, can influence slope of phase 4 (if flat: no net change)
if more + charge in, may reach threshold, shows automaticity (pacemaker cells)
Na+/K+ ATPase (sodium pump) (Na+ out, K+ in)
Na+/Ca2++ exchanger (Ca2+ out, Na+ in)
Na+ channel blockers may ??
suppress slope of Phase 0, may depress rate of depolarization
abnormal AP can spontaneously arise from cardiac sites other than the SA node (sometimes called ectopic sites) if ??
K+ too high or too low (e-lyte imbalance) ischemia acidosis scar tissue drugs abnormal cardiac anatomy (WPW) abnormal automatic nerve activity
abnormal AP formation: steep slope in phase 4
(also abnormal conduction)
abnormal AP formation
EADs and DADs
triggered by a previous AP
early after depolarizations (EADs) that “pop out” of phase 3
should be refractory!
esp. in Purkinje and Ventricles
can be due to ischemic conditions or if duration of AP is lengthened, slow HR, low EC K+ and certain AP-prolonging drugs
if happen earlier, involve Ca2+ current, if later, involve both Na+ and Ca2+ current
