Antiarrhythmics

no longer used for rhythm control, modestly effective, very
Moderate Na channel Blocker which
also blocks K channelsprolongs
QRS&QTaction potential; reduce
Quinidine (Antiarrhythmic automaticity and conduction velocity
Class IA) (Phase 0 and phase 3)
Increased TdP = hypotension syncope
toxic
supraventricular and ventricular arrhythmias like atrial
fibrillation & atrial flutter (moderately effective), ventricular
extrasystoles and VT(poorly effective)
Major clinical use: atrial fibrillation, atrial flutter, &
ventricular tachcycardia
and sudden death within the 1st few
days; Nausea, diarrhea, abdominal
cramping; Cinchonism = vertigo, HA,
tinnitus, psychosis, blurred vision; rash, Do not use in pt with long QT Rarely used;has a vasodilator effect so can be used in reduced
thrombocytopenia, hemolytic anemia;lupoid syndrom, TdP history, or vent function or HF; also has a indirect anticholinergic effect that
hepatitis and 2X to 3X increase in mortality hypokalemia (increases TdP) Put Na in your tonic and call it quinidine will decrease vagal tone and may facilitate condion in the AV node

Na channel blocker; Prolongs APD

and refractoriness (K channel effect);
slows conduction and decreases
automaticity and excitability of the
myocardium and Purkinje fibers. N-
acetyl-procainamide (procainamide
metabolite) prolongs APD and
Procainamide refractoriness in atrial and venticular
(Antiarrhythmic mixed myocardium and prolongs the QT
Class IA & III) interval. (Phase 0 and phase 3)
Used for Supraventricular and ventricular arrhythmias;
acute re-entrant supraventricluar tachycardia and atrial fib and
flutter associated with Wolff-Parkinson-White syndrome
(see extra notes)
Major clinical use: atrial fibrillation, atrial flutter, &
ventricular tachcycardia
Salty (Na) old man weiding his cain in NAPA
valley, whacking hot Lupus chick, giving her Absorbed rapidly and is 100% orally bioaviable; i.v. loading
lupus-like syndrome!! arrhythmia may be Do not use in pt with long QT butterfly rash; Rem: its not HIPP to get drug dose must be given slowly, so limited to clinical situations with
aggravated, development of TdP; syndrom, TdP history, or induced-LE - (Hydralizine, INH, Phenytoin, adequate time available; Does not increase digoxin levels;
agranulocytosis, BM depression hypokalemia Procainamide) cimetidine and ranitidine decrease clearance 10-50%

moderate Na channel blocker: Increase Broad range of supraventricular and ventricular

Disopyramide
(Antiarrhythmic Class IA)
venticular refractoriness and prolong the
QT inverval (reduces automaticity and
conduction velocity - phase 0), also
increases AP duration. (Phase 0 and
phase 3)
arrhythmias (similar to procainamide and quinidine) Loading dose not recommented, risk of HF or anticholinergic SE;
Moderately effective for atrial arrhythmia and poorly effective rapid fluctuations in plasma concentration; Phenytoin, rifampicin,
for ventricular arrhythmia Remember: dis o' pyramid sitting in sand of Na, and phenobarbital increase hepatic metabolism (elimination);
Major clinical use: atrial fibrillation, atrial flutter, & anticholinergic SE - stops peeing, can't piss or poop (anticholinergic), just wants 1 depression of contractility from co-admin with beta-adrenergic of
ventricular tachcycardia pooping, salivating impaired ventricular function Ass (1A) movement CCB

Class 1B
Reduce automaticity
CNS symptoms: seizures!! (mental Shorten APD (narrow QRS)
modest Na channel blockers (both acute rapid suppression of V arrhythmias, raises status changes), drowsiness, dyarthria, Slow conduction velocity
active and inactive Na channels) ventricular fibrillation threshold as well as suppresses dysesthesi, and coma; can depress cardiac Remember: class I be (B) ventin (works only on Have little or no effect on atrial tissue
Reduce automaticity arrhythmias caused by abnormal automaticity (observed pt function leading to decreased clearance, ventricle) with the short fuse temper (shortens all other classes work above ventricles
Lidocaine (Antiarrhythmic Shorten APD (narrow QRS) continuoulsy for SE), no atria effect; very effective membrane and produce greater SE; sinus node AP) Moderately effective for ventricular arrhythmia
Class IB) Slow conduction velocity stabilizer (numbing) dysfunction only used for V!!
CNS symptoms: seizures!! (mental
modest Na channel blockers (both status changes); dose related tremor, Remember: the Mexican (Mexiletine) injected
active and inactive Na channels) ventricular arrhythmias & refractory arrhythmias; useful in visual blurring, dizziness, dysphoria, and his toe (tocainamide) with lidocaine to numb Typically hepatic metabolism (CYP2D6), can be increased with
Reduce automaticity pts with torsades de pointes (TdP) or long QT syndrome (if nausea; thrombocytopenia and postivie the 1 Bee sting (class IB), but goes into a phenobarbital, phenytoin, or rifampicin; Pts with hepatic CYP2D6
Mexiletine (Antiarrhythmic Shorten APD (narrow QRS) other drugs contra), no effect in atrium; very effective ANA; worsen heart block with high seizure and wishes he'd injected dilantin deficiency are dependent on renal excretion. (notice, quinidine
Class IB) Slow conduction velocity membrane stabilizer (numbing) concentration instead inhibits the CYP2D6 Ez)
modest Na channel blockers (both
active and inactive Na channels)
Reduce automaticity
Tocainamide Shorten APD (narrow QRS)
(Antiarrhythmic Class IB) Slow conduction velocity similar to lidocaine
Effective for Atypical Ventricular Tachycardia;
Phenytoin [Dilantin] more typically used for seizures (also a membrane stabilizer,
(Antiarrhythmic Class IB ) Na channel blocker arrthymia in brain) Remember: die laughing so had a seizure

highly effective Na channel blocker; proarrhythmia!!; CHF; CNS=blurred drug interactions: cimetidine
Prolongs PR and QRS (prolongs AP), Potent inhibitor of ventricular arrhythmia; effective vision, headache, ataxia;decreases LV its clearance its half-life;
Flecainide (Antiarrhythmic reduces automaticity and conduction stabilization of atrial rhythm; supraventricular arrhythmias in function and depresses the SA node in pt digoxin, propranolol, & Remember: flick a cain in someones one eye eliminated by the liver (CYP2D6) and kidney(so not effected by
Class IC) velocity in A and V; negative inotrope pt with no structural heart dz with SA node dysfunction amiodarone its levels and they can't see (1C) CYP2D6 deficiency except in renal insufficiency)

highly effective Na channel blocker;

Prolongs PR and QRS (prolongs AP),
Encainide (Antiarrhythmic reduces automaticity and conduction Potent inhibitor of ventricular arrhythmia; effective
Class IC) velocity in A and V; negative inotrope stabilization of atrial rhythm; proarrhythmia!!

highly effective Na channel blocker; drug interactions: increases

Propafenone
(Antiarrhythmic Class IC)
Prolongs PR and QRS (prolongs action
potential), reduces automaticity and
conduction velocity in atria and
ventricles; negative inotrope; structurally
similar to propanolol so= blocker
digoxin, theophylline,
(similar to Flecainide) many arrhythmias, supraventricular cyclosporine levels and warafin
arrhythmias like atrial fibrillation in pt w/o structural heart dz; effects;cimetidine increases its eliminated by the liver CYP2D6; if CYP2D6 deficiency have slow
potent inhibitor of ventricular arrhythmia; effective proarrhythmia!! nausea, vomiting, metallic levels;phenobarbital, phenytoin, Prop a phone against Kofi in one sea (1C), the elimination of propafenone and develop significant receptor
stabilization of atrial rhythm taste to food rifampin decreases its levels sea is rough (proarrhythmia) antagonism at low doses

Dofetilide (Antiarrhythmic
mixed Class IC & III) similar to Flecainide similar to Flecainide similar to Flecainide

See adrenergics; indirect effect via

reduction of sympathetic receptor activity
and membrane stabilizing activity; mild
effect on automaticity and conduction
velocity; greatest effect is to slow AV
node conduction, also decrease SA
node automaticity and increase AV node
refractory period
Severe systolic heart failure
ventricular tachycardia, supraventricular arrhythmias, also (from massive myocardial
AV node re-entry, atrial fibrillation, and atrial flutter; congenital damage, RV infarction, or acute
long QT syndrome; prevents recurrent episodes of high doses=fatigue and depression; valvular regurgitation) and
ventricular tachycardia and reduces symptoms of bronchospasm, bradycardia and AV block, active wheezing from reactive esmolol, ultra short half life=9min, used for atrial fibrillation and
palpitations and sudden death in pt w/ prior MI myocardial contractility, impotence, CHF airway dz atrial flutter after surgery

proarrhythmia, bronchospasm, worsens

Sotolol (Antiarrhythmic
Class III)
& K & Na & Ca channel blocker;
prolongs QT interval and cardiac
refractoriness;slows sinus rate and
negative inotrope (slows repolarization)
heart failure;instability in pt w vent Remember: Jaba the Hut saying Sotolol
arrhythmias post MI;TdP in those w (meaning solo) for Han Solo, who is a master
bradycardia, prolonged QT intervals, and bounty hunter and will pull in any criminal,
all types of arrhythmias ie supravent and vent arrhythmias, hypokalemia;normal side effects of including & K & Na & Ca channel blocker almost as good as amiodarone; eliminated by the kidney w half life
cannot be used in patients with heart failure blockers criminals of 12hrs

Irreversible pulm fibrosis!!

Amiodarone
(Antiarrhythmic Class III;
has class I, II, III, and IV
activity)
Ibutilide (Antiarrhythmic
class III)
Dofetilide (Antiarrhythmic
class III)
Dihydropyridine group
(nifedipine, amlodipine,
nitrendipine, isradipine,
nisoldipine --
Antiarrhythmic class IVs)
Diltiazem (non-
dihydropyridine
antiarrhythmic class IV)
Verapamil (non-
dihydropyridine
antiarrhythmic class IV)
& K & Na & Ca channel blocker;
prolongs PR and QT; slows sinus rate
(slows repolarization); prolongs AP in
fast-response AP and prolongs effective
refractory period
K channel blocker; prolongs PR and QT
(slows repolarization) atrial fibrillation or flutter
K channel blocker; prolongs QT
Ca channel blockers (CCB), SM
selective; see renal CCB; slow
conduction velocity, phase 0 of node
Ca channel blocker; slows AV node
conduction (moderately), myocardial
selective; slows conduction velocity,
phase 0 of node
CCB: Most potent to AV node
conduction (also SA node); negative
inotrope; myocardial selective; slows
conduction velocity (phase 0) and
increase refractoriness in tissues with
slow-response AP
Hepatotoxicity (jaundice and cirrhosis);
hype- & hyporthyroidism, corneal
deposits; agranulocytosis, bluish
discoloration of skin & photodermatitis,
nausea, constipation, bradycardia, Remember: Amy and Yoda sitting together
ONLY used for life-threatening (refractory) Ventricular hypotension with IV due to contractility eatting bananas (K), yoda got corneal deposits
arrhythmias or Atrial fibrillation unresponsive to other and peripheral vascular resistance in eyes and is bitch'n because he has
antiarrhythmatics (AV nodal re-entrant tach and Wolff- 1-2% chance proarrhythmia (long QT drug interactions: digoxin and pulmonary fibrosis and toxic liver, but stoked
Parkinson-White syndrome and sudden death post MI or HF) syndrome; should first be started on an inpt cyclosporine levels and cause he can have a prolonged orgasm (half metabolized to desethyl metabolite (DEA) in the liver; half life of
Most efficacy of rhythm control among the antiarrhythmics basis) wafarin effects life) 5hrs to 30days (Cecil says 103days); IV HAS A RAPID EFFECT
dont give to those w
TdP (esp in women w vent function or hypokalemia,
electrolyte disoders--all TdP), heart hypomagnesemia or a QTc
block, hypotension, nausea >440msec oxidative hepatic metabolism and cleared by the kidney
TdP; drug interactions which increase Rem: Do fret, I lied (Do-fet-i-lide)
levels: erythromycin, diltiazem, cimetidine, - though your heart can be fixed
atrial flutter and atrial fibrillation; maintenance of sinus or ketoconazole; causes massive by bananas (K), it causes eliminated by liver (CYP3A4) and kidney; half life=8-10 hrs but
rhythm after reversion diarrhea! massive diarrhea 12% to 18% lower in women
reflex tach due to vasodilation; edema
small effect on AV conduction and arrhythmia and orthostatic hypotension
slows vent rate with atrial fibrillation or flutter and moderate in LV contractility,
prevents AV nodal re-entrant tach bradycardia and hypotension
Indicated for atrial fibrillatoin and atrial flutter; V response peripheral edema, moderate in LV
in SVT and slows V rate w/ A fib or flutter and prevents AV contractility (V. Fib.) and hypotension
nodal re-entrant tach; HTN and peripheral vasospasm (peripheral vasodilation); constipation; CHF (because of decreased
disorders hemodynamic collapse inotropic effect)

promotes atrial and vent irritability;

slows AV node conduction (Vagotonic hypokalemia, loss of appetite, nausea,
action), and depress SA node; vomiting, diarrhea, blurred vision & yellow-
conduction velocity and slows V green halos (xanthopsia), confusion,
response to SVT; force of heart drowsiness, dizziness, nightmares, Wolff-Parkinson-White
contraction via inhibition of the Na+/K+ agitation,depression; do not give with syndrome (direct
Digoxin (digitalis) see also ATPase pump less Na to trade for Ca Atrial fibrillation & atrial flutter; and CHF not be controlled quinidine (displaces digoxin from binding connection/reentry tachy - dig
above - cardiac glycosides to exit cell by other med (not antiarrhythmic) sites on albumin) would exacerbate) derived from digitalis

facial flushing, dyspnea, or chest pressure dont use for AFib, sick sinus
DOC for acute Paroxysmal SVT caused by re-entry thru AV lasts <60 sec; sometimes nausea, syndrome, or 2 and 3 heart
Adenosine (antiarrhythmic Slows AV node conduction - causes node; lightheadedness, headache, sweating, block unless they have a Half life of 1.5 to 10 sec (shortest half life of any drug);
class V) transient heart block in the AV node diagnostic tool (see extra notes) palpitation, hypotension and blurred vision pacemaker metabolized in the plasma

Prolongs APD and refractoriness (K

Procainamide
(Antiarrhythmic Class III)
channel effect); slows conduction and
decreasses automaticity and excitability
of atrial and ventricular myocardium and
Purkinje fibers. N-acetyl-procainamide
(aka NAPA, procainamide metabolite)
prolongs APD and refractoriness in atrial
and venticular myocardium and polongs Used for Supraventricular and ventricular arrhythmias Absorbed rapidly and is 100% orally bioaviable; i.v. loading
the QT interval (Reduce automaticity (similar to quinidine, used if quinidine not effective); acute re- Arrhythmia may be aggravated, Do not use in pt with long QT dose must be given slowly, so limited to clinical situations with
and conduction velocity effects phase entrant supraventricluar tachycardia and atrial fib and development of TdP; lupus-like syndrome, TdP history, or adequate time available; Does not increase digoxin levels;
4 and 0) flutter associated with Wolff-Parkinson-White syndrome syndrome; agranulocytosis hypokalemia cimetidine and ranitidine decrease clearance 10-50%

Class 1A:
1. Reduce automaticity (phase 4, reduce slope of upstroke,
AP becomes broader)
2. Prolong action potential duration
3. Reduce conduction velocity (phase 0, slope also reduced)
Note: (phase 3 affected, not 4, according to Lange)
Antiarrhythmic Class III: prolong duration of cardiac action
potential (AP) and refractoriness;most potent class of
antiarrhythmic drugs, effective for rhythm disturbances in all
tissues; combo of blocker, Ca channel blocker and Na
Channel blocker along with primary effect on repolarization
current (basically does everything the other classes do put
together)
Antiarrhythmic Class IA include quinidine, procainamide,
and disopyramide - increase venticular refractoriness and
prolong the QT inverval
Antiarrhythmic Class Class IB include lidocain, mexiletine,
and tocainide - modest Na channel blockers that shorten
the action potential duration (APD) and refractoriness with
little effect on PR, QRS, or QT intervals
Antiarrhythmic Class Class IC include flecainide and
propalenone - potent Na channel blockers that slow
conduction velocity, little effect on repolarization, and increase
PR and QRS intervals, little change on QT interval
Antiarrhythmic Class II: beta adrenergic antagonist, effective
for supraventricular arrhythmias and tachyarrhythmias caused
by excessive sympathetic activity; limited efficacy for severe,
life-threatening ventricular arrhythmias; mech unknown; only
drugs effective in preventing sudden cardiac death with
MI survivors
Most potent class of antiarrhythmic agents (meaning Class III)
Effective for rhythm disturbance in all tissues
Agents possess combination of mild beta blocker, calcium
channel blocker and sodium channel blocker activity along
with primary effect on repolarization current (K current)
Amiodarone:
prolonged half-life of 30 days - makes difficult to use to
reach steady state (4-5 half lives) requires half a year (3
months for effect), and if make a mistake, takes 5 half lives to
get ride of , must follow pt closely (have foresight)
Rapid effect when given IV
Side Effects
Hepatotoxicity
Hypo and hyperthyroidism
Corneal deposits
Irreversible pulmonary fibrosis (permanent)
Antiarrhythmic Class IV: Ca channel antagonists; dont
affect the Phase2 plateau???; poor effect as direct
antiarrhythmic for atrial or vent arrhythmias, most effective
on slowing conduction velocity (Phase 0) in nodal
tissues; useful for the control of vent rate in SVT
CCB and beta blockers have ~same effect in heart - slow
conduction velocity in the AV node (prevent SVT from getting
to V)
Used diagnostically to determine whether ventriclar
tachycardia was induced supraventricularly or
ventricularly
Antiarrhythmic Class III: prolong duration of cardiac action
potential (AP) and refractoriness
Drug interactions: increases digoxin level and warfarin
effect;heparin, verapamil, cimetidine increases its levels;
phenobarbital, phenytoin, rifampin decreases its level
Class 1A effects also (procainamide is a mixed class drug)
Reduce automaticity (phase 4, reduce slope of upstroke, AP
becomes broader)
Prolong action potential duration
Reduce conduction velocity (phase 0, slope also reduced)
Antiarrhythmics: limited usefulness because of toxicity and
lack of efficacy; may worsen mortality. Every agent has
potential for serious toxicity. Classified according to
electrophysiology (see Cecil 341) for Vaughan William s Class
(I, II, III, & IV)
Synergistic depression of myocardial function with combo of
other antiarrhythmic agents (especially propranolol). Pts with
heart failure (HF) achieve lidocaine levels that are double
the levels of normal pts (reduce dose by half)
Class 1C
Reduce automaticity and conduction velocity in atria and
ventricles
Prolong action potential duration
Major side effect is proarrhythmia
Premature ventricular contraction (PVC) - common in pts
with and without HD (found in 60% of adults on Holter
monitoring), do no specifically suggest any underlying dz,
usually requires no tx; beta blocker would be DOC if it effects
daily life of pt
hypothyrodism SE either as a result of its high iodine content Dose dependent toxicity especially with long-term use
or by inducing thyroiditis (avoid use in young pts)
drug interactions: carbamazepine and dipyridamole
pretreatment its potency; caffeine and theophylline
antagonize it
Procainamide:
Moderately effective for atrial or ventricular arrhythmia
Metabolized in liver to active component NAPA
this metabolite is more effective (acetly group)
must check prodrug and metabolite to prevent toxcity
Reduce automaticity and conduction velocity
effects phase 4 and 0
Universal adverse effect is lupus
Action Potential All phases common to nodal and non-nodal Electrolyte shift in Atrial or Ventricular tissue (non-nodal) Electrolyte shift in Nodal Tissue
Electrolyte shifts create electrical activity Phase 0: Rapid depolarization Phase 0: Sodium Phase 0: Calcium and Sodium
ALL Antiarrhythmic drugs have narrow therapeutic Four phase action potential demonstrates the various Phase 1: Depolarization overshoot Phase 1: Sodium channel closes Phase 1: Sodium channel????????
index, variable metabolism and clearance; many stages of activity Phase 2: Plateau Phase 2: Calcium channel open Phase 2: Calcium channel
(especially class I) inhibit Cytochrome P-450 (which is Electrolytes associated with each phase differ in nodal Phase 3: Repolarization Phase 3: Potassium rectifier Phase 3: Potassium rectifier All class I anti-arrhythmic agents are use-
absent in 7% caucasians and 2% blacks); many drug eliminated mainly by the liver and some by the kidney; elderly vs. non-nodal tissue Phase 4: Instrinsic depolarization Phase 4: Sodium leak Phase 4: Sodium leak dependent, meaning that they tend to be more acive
interactions requires lower dose due to reduced clearance at ion channels that are depolaring more frequently
WPW syndrome is best txed with a class IA agent which increase refractoriness of the bypass track and "break" the reentry
tachyarrhythmia. Other agents (adenosine, BB, and digoxin (&CCB?) should be avoided in a wide complex preexcitation
syndrome such as WPW because they may accelerate the ventricular rate and cause the rhythm to degenerate to Vfib (these
agents act by inhibiting the AV node and thus increase conduction down accessory pathway; also class IB agents shorten the
repolarization by decreasing the AP duration and thus also can increase the ventricular response to an SVT). If a pt has
evidence of WPW on ECG and is hemodynamically unstable, DC cardioversion should be first-line therapy
Disopyramide:
Moderately effective for atrial arrhythmia and poorly effective for
ventricular arrhythmia
Antiarrhythmic Class I (A, B, & C): local anesthetic or Reduces automaticity and conduction velocity
membrane-stabilizing activity; block fast inward Na Side effects include decreased contractility and urinary retention
channel, decreasing maximum depolarization rate, Vmax, has anticholinergic effects - stops peeing, pooping, salivating
of the AP (phase 0); basically Na Channel Blockers
Lidocaine works on slightly depolarrized or ischemic tissue Note: Infiltration of inflammation mediators and necrotic materials
more so than normal tissue, due to its state-dependent lower tissue pH (eg abcess) and render lidocain anestheic less
blocking. Therefore, use lidocaine (IV) to suppress acute effective (lidocaine is a weak base, does not work when
MI-associated ventricular arrhythmias protonated)
Class IC do same thing as class1A, but more powerful
very powerful side effects, the worst SE is accutally
worsening arrhythmia
Class IC kills people; thus, they are not used as first line agents
Benefits of IV BB therapy early in acute infarction
reduces myocardial O2 consumption (negative
inotropic and chronotropic actions) and has a direct
antiarrhythmic effect. Do not withhold in pts with sinus
bradycardia, diabetes, or well-controlled asthma (all BB are beneficial in longterm tx of pts follwing MI if they have
relavite contraindications) - rhythm disturbances tend to be evidence of recurrent ischemia or have sustained a Q-wave MI
reversibble and are easily treated with temoproary pacing (give BB, ACEI and ASA). Howevere, BB have no benefit in pts
if symptomatic with small or non-Q-wave MI (give ACEI and ASA)
Increased AP duration causes the increase in QT interval
When macula densa sense increase NaCl, they send signal (via extraglomerular mesanginum) to granular cells to secret
adenosine which vasoconstricts primarily the afferent a. (know that in most areas of the body adenosine is a vasodilator,
not so in the kidneys), decreasing GFR (moderate constriction; if severe constriction then GFR decreases because blood
flow becomes so stagnant that proteins clog up on exam always assume moderate efferent a. constriction)