differences in ion concentrations (negative on the inside relative to the outside)
where is the site of blockade in torsades de pointes induced by anti-arrhythmic drugs
the delayed rectifier IKr
what natural stimulus source paces cells with automaticity
sinoatrial node SA
two basic abnormalitied in the stimulus to discharge
abnormal impulse generation (ectopic foci)
abnormal impulse conduction
an abnormal portion of tissue that develops "automaticity"
ectopic foci
unidirectional blockage of conduction down one path of parellel conduction pathways, feedback loop results in self propagating impulses
re-entry arrhythmias
most common cause of supraventricular tachycardias
re-entry arrhythmias
automaticity arrhythmias
ventricular arrhythmias
this class agent has a MOA - block Na+ channels, slow conduction velocity, prolong refractoriness, decrease automaticity of sodium-dependent tissues
class I
this subclass of anti arrhythmic block K+ channels (prolonged recovery phase) resuling in QRS widening and QT longation
subclass 1A
these two subclasses are used in Atrial and ventricular arrhythmias
1A
1C
this subclass does not block K+ channels but shorten repolarization phase
1B
this subclass is used in ventricular arrhythmias not atrial
1B
this subclass has no effect on repolarization phase but profoundly slow conduction velocity resulting in QRS widening
1C
this class has a MAO of beta adrenergic agonist with decreased heart rate by blocking norepinephrine and epinephrine receptors
antagonizes thyroid hormones effects
II
this class is indicated for - slow ventricular rate in ventricular rate in atrial flutter/fibrillation and paroxysmal supraventricular tachycardia(PSVT)
II
side effects of this class include bradycardia and all other side effects that go with beta-blockers
II
this class has a MOA - block K+ channels leading to prolonged repolarization and QT longation, except ibutilide
III
this class agent is indicated for
atrial and ventricular arrhythmias
conversion of atrial flutter/fibrilation
III
this class agent MOA - Ca+2 channel blockers decreasing the heart rate
IV
this class agent is indicated for slow ventricualr rate in atrial flutter/fibrillation and PSVT
IV
class IA agent
80% hepatic metabolism
2-4 days to reach steady state
adverse effect of GI irritation
a polymorphic ventricular tachycardia with hypokalemia and/or hypomagnesium
cinchonism
metabolized by CYP3A4
quinidine salts - quinora
class IA agent
actually two drugs
30% lupus like syndrome (slow acetylators)
1% agranulocytosis
procainamide HCL - pronestyl
N-acetyl - NAPA
class IA agent
very potent negative inotropic properties
IND - idiopathic hypertropic subaortic stenosis
has an inactive metabolite with potent anticholinergic properties
disopyramide phosphate - norpace
class IB agent
indication - ventricular arrhythmias only
extensive first pass effect
t 1/2 - 1.5 hrs
hepatic metabolism to two active and potentially neurotoxic metabolites leading to drowsiness
adverse effects - monitor closely for CNS toxicity, dizziness, speech disturbances, respiratory depression, seizures
lidocaine HCL - xylocaine
this drug comes in a lidopen auto inj.
lidocaine
class IB
ind - ventricular arrhythmias only
adverse effects - monitor closely for CNS toxicity
possible agranulocytosis and pulmonary fibrosis
mexiletine HCL - mexitil
class IC agent
uses dropped off due to increased mortality
decrease left ventricular function due to negative inotropic properties
IND - PSVT, paroxysmal atrial fibrillation/flutter
t 1/2 - 20hrs
flecainide acetate - tambocor
class IC agent
ind - PSVT, paroxysmal atrial fibrillaton/flutter
100% hepatic metabolism to a metabolite that has active beta-blocker properties
drug interactions - inhibits hepatic metabolism of some drugs
propafenone HCL - rythmol
class IC agent
ind - PSVT, paroxysmal atrial fibrillation/flutter
capable of inducing its own metabolism
adverse effects - N/V
moricizin HCL - ethmozine
class III agent
clearly demonstrated to decrease arrhythmia in post MI and heart failure patients
t 1/2 - 45 days
adverse effects hypo/hyperthyroidism
containd Iodine
amiodarone HCL - cordarone
how can we avoid accumulation and toxicity in class III agents
add and ester group
new product for 2009
non-iodinated analog of amiordarone
no thyroid, pulmonary, ocular toxicity
MOA - unknown because it has all 4 properties of vaughn-williams classes
dronedarone - MULTAQ
class II agent
IV only
adverse effects because of IV faster drug infusion - hypotension, N/V
digoxin toxicity is aggravated by catecholamines that are released by this drug
bretylium tosylate
a class II & III agent
MOA - beta blocker and K+ channel blockade
100% absorbed
excreted unchanged in the urine
racemic mixture - pure d-enantionmer has been shown to increase mortality by 65%
sotalol
class III agent
blocks K+ outflow
dofetilide - tikosyn
class III agent
promotes Na+ influx
may mask arrhythmias caused by digoxin
ibutilide - corvert
class IV agents
only 2 approved by the FDA for arrhythmias
posible alternative medicines to beta-blockers for arrhythmias
contraindicated in systolic dysfunction due to negative inotropic effects
CYP inhibitors
verapamil
diltiazem
these three drugs are L-type Ca+2 channel blockers
verapamil
diltiazem
1,4-dihydropyridine
misc agent
MOA - acts at purine receptors to slow or block conduction through the AV node
diagnostic aid in determining wide QRS complex
t 1/2 - 1-10 sec.
contraindicated in sich sinus syndrome, second or third degree AV block, patients with asthma or COPD
drug interactions - caffeine and theophylline block their receptors, large doses are needed
adenosine - adenocard
misc agent
low adenosine A2A receptor agonist - increases vasodilation and coronary blood flow
IND - radionuclide myocardial inaging
Interactions - no methylxanthine 12 hours before
aminophylline can reverse persistant adverse reactions
regadenoson - lexiscan
interventional cardiology method treatment to kill off the problematic tissue
radio frequency ablation (RFA)
patients reposition pacemaker so it comes out of place and can pull the lead out
twiddler syndrome
these cardiovascular agent consist of 5 protein subunits
regulate smooth (cardiac) muscle contraction
calcium channel blockers
three prototypical chemical classes of Ca+2 blockers
phenylalkylamines
1,4 dihydropyridines
benzothiazepine
name the three status equilibrum states that are a function of stimulus frequency and membrane potential
open
resting
inactivated
what status of equilibrium does phenylalkylamines and benzothiazepine bind to
AFTER the channel is open
what status of equilibrium does 1,4-dihydropyridines act on
open or closed
indication of calcium channel blockers
control of angina and hypertension
verapamil and diltiazem have both cardiac and vascular actions?
true
1,4-dihydropyridines have more pronounced what actions
vascular
two side effects of calcium channel blockers
may precipitate CHF
edema of the hands and feet
calcium channel blocker
a benzothiazepines
Slow release products only
incompatible with furosemide
diltiazem HCL - cardizem
calcium channel blocker
phenylalkylamines
IND - chronic stable angina
