anti-arrhythmic agents Flashcards
arrythmias are classified by
site of origin of abnormality
complex on ECG
rhythm
rate
what are the 4 mechanisms of arrhythmia production?
altered automaticity
delayed after-depolarization
re-entry
conduction block
altered automaticity
latent pacemaker cells tack over the SA node’s role
delayed after depolarization
normal action potential of cardiac cell triggers a train of abnormal depolarizations
re-entry
refractory tissue reactivated repeatedly and rapidly due to unidirectional block which causes abnormal continuous circuit of APs
conduction block
impulse fail to propagate in non-conducting tissue
when do cardiac arrhythmias require treatment
when they cannot be corrected by removing the precipitating cause
when hemodynamic stability is compromised
when it predisposes to more serious cardiac arrhythmias or co-morbities
name some non-pharmacologic treatments of arrhythmias
acute - vagal maneuvers, cardioversion
prophylaxis - radio-frequency catheter ablation, implantable defibrillator
pacing - external, temporary, permanent
class I agents - moa
block sodium channels
this depresses phase 0 of the fast action potential
= depresses depolarization (decreased rate and slowing conduction velocity)
aka “membrane stabilizing agents”
what are class I agents used to treat?
SVT, a fib, WPW
class IA agents moa
intermediate Na channel blocker
slows conduction velocity and pacemaker rate
- decreased depol (phase 0)
- prolonged repol (must block K channels to some degree)
- increased AP duration
direct depressant effects on SA and AV node
what do you use class IA agents for
atrial and ventricular arrhythmias
name the class IA agents
quinimide (prototype) - no longer available
procainamide
disopyramide (Norpace)
why aren’t class IA drugs commonly used?
they cause toxicity and may precipitate heart failure
what is disopyramide
PO agent that suppresses atrial and ventricular tachyarrhythmias
what are the negative side effects of disopyramide
myocardial depressant effects and can precipitate CHF and hypotension
when do you use procainamide
used in the treatment of vent tachycardias (less effective with atrial)
was once part of ACLS algorithm
dose of procainamide
loading: 100 mg IV q5min until rate controlled (MAX = 15 mg/kg)
then
infusion: 2-6 mg/min
side effects of procainamide
myocardial depression leading to hypotension
syndrome that resembles lupus
therapeutic levels of procainamide
= 4-8 mcg/ml
how protein bound is procainamide
15%
what is the half life of procainamide
2h
what are the class IC agents
flecainide (prototype)
propafenone (PO)
class IC moa
slow Na+ channel blocker (slow dissociation) so does not vary much with cardiac cycle
causes potent decrease of depolarization rate (phase 0) and decreased conduction rate with increased AP
markedly inhibits conduction through His-Purkinje system
Flecainamide uses and side effects
effective in treatment of suppressing PVS and ventricular tach, also atrial tach, WPW (reentry syndrome)
PO
has pro-arrhythmic side effects **can cause sudden death with v-fib
propafenone uses and side effects
suppression of ventricular and atrial tachyarrhythmias
PO
has pro-arrhythmic side effects - can cause torsades and sudden death with vfib
what are the class IB agents
lidocaine (prototype)
mexiletine (PO)
phenytoin
class IB moa
fast Na channel blocker = fast dissociation
alters AP by inhibiting Na ion influx via rapidly binding to and blocking sodium channels
produces little effect on max velocity depol rate, but shortens AP duration adn shortens refractory period
decreases automaticity
lidocaine use and SE
used in treatment of ventricular arrhythmias
particularly effective with suppression reentry rhythm: V tach, v fib, PVCs
don’t use to treat v fib after acute MI because it increases mortality d/t bradyarrhythmias
dose of lidocaine
IVP: 1-1.5 mg/kg
gtt: 1-4 mg/min (max dose 3 mg/kg)
how protein bound is lidocaine
50%
how is lidocaine metabolized
hepatic metabolism - cyp450
- active metabolite prolongs elimination half time
extensive first pass metabolism when taken PO
what can alter metabolism of lidocaine
impaired by
- drugs such as cimetidine and propanolol
- CHF, acute MI, liver dysfunction
- General anesthesia
can be induced by barbs, phenytoin, or rifampin
describe lidocaine elimination
10% eliminated renally
adverse effects of lidocaine
hypotension, bradycardia, seizures, cns depression, drowsiness, dizziness, lightheadedness, tinnitus, confusion, apnea, myocardial depression, sinus arrest, heart block, ventilatory depression, cardiac arrest and can augment pre-existing neuromuscular blockade
what is mexiletine used for
chronic suppression of ventricular tachyarrhythmias - PO agent
dose of mexiletine
150-200 mg Q8H
why can mexilitine be taken orally and lidocaine cannot
amine side group allows for PO admin because it avoids first pass metabolism
phenytoin uses
effects resemble lidocaine
used in suppression of ventricular arrhythmias associated with digitalis toxicity
can also be used for other ventricular tachycardias or torsades
how is phenytoin given
IV in NS
will precipitate in D5W
can be painful in peripheral IV
dose of phenytoin
1.5 mg/kg every 5 minutes up to 10-15 mg/kg
therapeutic blood levels of phenytoin
10-18 mcg/ml
how is phenytoin metabolized
by the liver
how is phenytoin excreted
in the urine
what is the elimination half time of phenytoin
24 hours
what are the adverse effects of phenytoin
CNS disturbances, partially inhibits insulin secretion, bone marrow depression, nausea, ataxia, slurred speech, severe hypotension with rapid admin
class II moa
beta-adrenergic agonists
depress spontaneous phase 4 depolarization resulting in SA node discharge decrease = slowing of heart rate and decreased mvo2
class II moa
beta-adrenergic agonists
depress spontaneous phase 4 depolarization resulting in SA node discharge decrease = slowing of heart rate and decreased mvo2
slows speed of conduction of cardiac impulses through atrial tissues and AV node resulting in prolongation of PR interval, increased duration of AP, decrease automaticity
prevents catecholamine binding to beta receptors
what are class II agents used for
treats SVT, atrial and ventricular arrhythmias
suppress and treat ventricular dysrhythmias during MI and reperfusion
treats tachyarrhythmias secondary to digoxin toxicity and SVT (afib/aflutter)
What are the class II agents
propanolol (prototype)
esmolol
metoprolol
what is the selectivity of propanolol
non-selective
what is the use of propanolol
to prevent reoccurence of tachyarrhythmia, both supraventricular and ventricular precipitated by SYMPATHETIC STIMULATION
what is the onset of propanolol
2-5 minutes
when would you expect peak effects of propanolol
10-15 minutes after given
what is the duration of propanolol
3-4 hours
what is the elimination half time of propanolol
2-4 hours
what are the cardiac effects of propanolol
decreased HR, contractility, and CO
increased PVR (bronchoconstriction d/t beta2 block), coronary vascular resistance
Decreased MVO2 (demand)
what is the selectivity of metoprolol
beta 1 selective
dose of metoprolol
5mg over 5 min
max dose 15 mg over 20 min
onset of metop
2.5 min
duration/half-life of metop
3-4 hours
how is metop metabolized
liver
when do you use metop
mild CHF
what is the selectivity of esmolol
selective for beta 1
what is the dose of esmolol
0.5 mg/kg bolus over 1 min, then 50-300 mcg/kg/min
what is the duration of esmolol
<10 mins = quick acting, short acting
how is esmolol metabolized
hydrolyzed by plasma esterases
in small doses, how does esmolol effect HR and BP
effects HR (decrease) without significantly decreasing BP
class III agents moa
block potassium channels which
- prolongs cardiac depolarization (cells don’t start to repol because VGKs dont open)
- increased AP duration (because K can’t efflux to bring cells back to baseline)
- lengthening repolarization (same as above)
PROPORTION OF CARDIAC CYCLE WHERE CELLS ARE EXCITABLE IS DECREASED = aka longer time in refractory aka cell isn’t susceptible to AP trigger
class III agent uses
treat supraventricular and ventricular arrhythmias
preventative in patients who have survived sudden cardiac death who are not candidates for ICD
control rhythm in Afib
- this is given prophylactically in cardiac surgery patients because there is a high incidence of afib
what is a negative ekg change caused by class III agents
prolongation of QT interval can lead to torsades
what are the class III agents
amiodarone (prototype) dronedarone ibutilide dofetilide (PO) sotalol
amiodarone moa
characterized as class III but also has I, II, and IV properties - aka it blocks K, Na, and Ca channels and its a beta agonist
however, it works primarily in phase II and III as a k channel blocker
uses of amiodarone
prophylaxis or acute treatment for atrial and ventricular arrhythmias (refractory SVT, refractory VT/VF, AF)
1st line drug for VT/VF when resistant to electrical defibrillation
“one of the most effective drugs at preventing arrhythmias in patients with HF”
dose of amiodarone
bolus 150-300 mg IV over 2-5 minutes, up to 5 mg/kg
then
1 mg/hr for 6 hours
then
0.5 mg/hr for 18 hours
what is the elimination half life
29 days - prolonged
how is amiodarone metabolized
hepatic with active metabolite
how is amiodarone excreted
biliary/intestinal excretion
what is the therapeutic plasma level for amio
1.0-3.5 mcg/ml
is amio protein bound?
yes 96%, extensively
describe the volume of distribution of amiodarone
large
amiodarone adverse effects
PULM TOXICITY (lung fibrosis d/t free O2 radicals in drugs) pulm edema ARDS abnormal LFT photosensitive rash grey/blue skin discoloration thyroid abnormalities corneal deposits TORSADES (arrhythmic effects) HEART BLOCK HYPOTENSION sleep disturbances CYP450 INHIBITOR!!!!!!
sotalol moa
primarily class III drug with some class II action aka K channel blocker with some nonselective beta agonism included
uses of sotalol
used to treat severe sustained v tach and v fib, to prevent reoccurrence of tachyarrhythmias (especially afib and aflutter)
side effects of sotalol
prolonged qt interval bradycardia myocardial depression fatigue dyspnea av block
what is a patient population you should use caution with when giving sotalol (think respiratory)
asthma because non selective beta antagonism action
how is sotalol excreted
urine
dofetilide and ibutilide uses and main SE
class III
used for conversion of afib or aflutter to NSR
used for maintenance of SR after afib or conversion of afib to sinus
SE: pro-arrhythmic d/t prolongation of QT interval
name the class IV calcium channel blockers
verapamil
diltiazem
nifedipine
where are calcium ion channels?
skeletal muscle cell membrane VSMC cardiac muscle mesenteric muscle neurons glandular cells coagulation
calcium channel blockers moa
block L-type channels selectively to interfere with inward calcium ion movement across myocardial and vascular smooth muscle cells
structure and area of action of verapamil
and moa at channel
phenyl-alkyl-amine at AV node
intracellular pore blocking of channel at binding site
structure and area of action of diltiazem
and moa
benzothiazepine at AV node
mechanism unclear
structure and area of action of nifedopine
and moa
1, 4-dihydropyridine at arterial beds
extracellular allosteric modulation of channel at binding site
structure and importance of L-type calcium channel
5 subunits
alpha 1 is the central part of channel and provides main path for Ca2+ to enter
this is a slow channel
important in determining vascular tone and cardiac contractility
vascular uses of calcium channel blockers
angina systemic hypertension pulmonary hypertension cerebral arterial spasm raynauds migraine
ca channel blockers dilate coronary arteries and decrease contractility of VSMC
non-vascular uses of calcium channel blockers
bronchial asthma
esophageal spasm
dysmenorrhea
premature labor (prevention)
effects of ca channel blockers
decreased contractility
decreased HR
decreased activity of SA node
decreased rate of conduction of impulses via AV node
vascular smooth muscle relaxation = decreased SVR and BP
- arterial > venous
decreased mvo2 (demand)
uses for calcium channel blockers
treatment of SVT, ventricular rate control in afib and aflutter
prevention of reoccurrence of SVT
NOT used in ventricular arrhythmias
verapamil structure highlights
phenylakylamine
synthetic derivative of papaverine
levoisomer is specific for the slow calcium channel
moa verapamil
depresses the AV node
negative chronotropic effects on SA node aka decreased HR
negative inotropic effects on myocardial muscle aka decreased contractility
moderate vasodilation on coronary as well as systemic arteries
clinical uses for verapamil
SVT vasospastic angina pectoris HTN hypertrophic cardiomyopathy maternal and fetal tachydysrhythmias premature onset of labor
protein binding of verapamil
highly protein bound - presence of other agents that are protein bound such as lidocaine, diazepam, propanolol increase its activity
absorption of verapamil
orally almost completely absorbed with extensive hepatic metabolism and almost none of the drug appears unchanged in the urine
oral and IV peak of verapamil
PO = 30-45 minutes IV = 15 minutes
elimination half time of verapamil
6-12 hours
6-8 on later slide?
dose of verapamil
2.5-10mg IV over 1-3 minutes (max dose 20mg)
continuous gtt 5 mcg/kg/min
what med is iv verapamil contraindicated with
beta blockers because it can cause a heart block
how is verapamil metabolized
hepatic with active metabolite norverapamil
how is verapamil excreted
in the urine and bile
side effects of verapamil
myocardial depression, hypotension, constipation, bradycardia, nausea, prolongs effects of NMBDs
site of action of diltiazem
AV node is prinicple site of action
what is the first line treatment for SVTs
diltiazem
what is the relative potency of diltiazem in comparison to the other class IV calcium channel blockers
intermediate between verapamil and nifedipine
what is the extent of CV depressant effects of diltiazem
minimal
clinical uses of diltiazem
SVT*** vasospastic angina pectoris HTN hypertrophic cardiomyopathy maternal and fetal cardiac dysrhythmias
dose of diltiazem
0.25-0.35 mg/kg over 2 minutes, can repeat in 15 minutes
infusion = 10 mg/h
oral onset and peak of diltiazem
15 minutes peaks in 30
protein binding of diltiazem
70-80%
excretion of diltiazem
bile and urine
what patients would need a decrease in dose of verapamil
liver disease
clinical uses of nifedipine
angina pectoris
primary site of action of nifedipine
peripheral arterioles
clinical effect on SA/AV node?
little to no effect
what is a HR concern for nifedipine
reflex tachycardia
what patients are at risk for myocardial depression with nefedipine?
patients with LV dysfunction or those on beta blockers
what are the routes of admin for nifedipine
IV, PO, sublingual
oral onset and peak
onset 20 minutes
peak 60-90 minutes
protein binding of nifedipine
90% protein bound
metabolism of nifedipine
hepatic
excretion of nifedipine
urine
elimination half time of nifedipine
3-7 hours
side effects of calcium channel blockers
cancer with long term use
cardiac problems
bleeding d/t interference with platelet function
constipation
vertigo, HA, flushing, hypotension, paresthesias, muscle wekaness
can induce renal dysfunction
what is the drug interaction of calcium channel blockers with inhalational agents
myocardial depression
what is the drug interaction of calcium channel blockers with NMBDs
can potentiate blocks
what is the drug interaction of calcium channel blockers with beta blockers
risk for heart block - particularly with verapamil
what is the drug interaction of calcium channel blockers with local anesthetics
verapamil increases risk of LA toxicity
what is the drug interaction of calcium channel blockers with dantrolene
verapamil and dantrolene can cause hyperkalemia due to slowing of inward movement of K ions which can result in cardiac collapse
what is the drug interaction of calcium channel blockers with digoxin
can increase the plasma concentration of digoxin by decreasing its plasma clearance
what is the drug interaction of calcium channel blockers with H2 antagonists
ranitidine and cimetidine alter hepatic enzyme activity and thus could increase plasma levels of CCBs
how do you reverse calcium channel blocker toxicity?
IV administration of calcium or dopamine
why are patients on CCB a bleeding risk
they interfere with calcium mediated platelet function
what can happen with abrupt d/c of CCBs
coronary vasospasm
adenosine moa
binds to A1 purine nucleotide receptors
- activates adenosine receptors to open K channels and increase K currents
- slows AV nodal conduction
what is adenosine used for
acute only to terminate SVT or for diagnosis of VT
dose of adenosine
6mg iv rapid bolus
repeated if necessary after 3 minutes, 6-12 mg iv rapid bolus
how affective is the first dose of adenosine vs the second dose
effective on first dose 60%
effective on second dose 90%
half life of adenosine
<10 seconds
elimination of adenosine
via plasma and endothelial cell enzymes
side effects of adenosine
excessive AV or SA nodal inhibition, facial flushing, HA, dyspnea, chest discomfort, nausea, bronchospasm
adenosine is contraindicated in which patients
asthma (causes bronchospasm) heart block (slows AV conduction)
digoxin mechanism of action
comes from foxblood plant - cardiac glycoside
increases vagal activity, thus decreasing activity of SA node and prolongs conduction of impulses through AV node by increasing refractory period
decreases HR, preload, and afterload
digoxin uses
for management of afib/flutter (controls ventricular rate) especially with impaired heart function
used to treat chf because it is a positive inotrope
dose of digoxin
0.5-1 mg in divided doses over 12-24 hours
onset of action of digoxin
30-60 minutes
half life of digoxin
36 hours
describe the therapeutic index of digoxin
narrow
0.5-1.2 ng/ml
describe the protein binding of digoxin
weak
how is digoxin excreted
90% by kidneys
considerations for elderly or those with renal impairment?
reduce dose and frequently check levels
adverse effects of digoxin
arrhythmias, heart block, anorexia, nausea, diarrhea, confusion, agitation
- potentiated by hypomagnesemia and hypokalemia
how to treat digoxin toxicity
phenytoin for ventricular arrhythmias
pacing
atropine
magnesium moa
works at sodium, potassium, and calcium channels
when do you use magnesium
torsades
dose of magnesium
1g IV over 20 minutes, can be repeated
