Anti-arrhythmic agents II Flashcards
Class 1 agents work by
blocking sodium channels which depresses phase 0; decreases in action potential propagation (decrease in depolarization rate) and slowing of conduction velocity
Class 1 agents are used to treat
SVT, AF, and WPW
Class 1A agents have direct depressant effects on
the SA & AV node
Class 1A agents work by
slowing conduction velocity and pacemaker rate
intermediate Na+ channel blocker
decreases depolarization rate
prolongs repolarization
Class 1A agents are used for
atrial and ventricular arrhythmias
Class 1A agents are eliminated by
hepatic metabolism
Class 1A agents can cause
a reversible lupus like syndrome
The class 1A drugs include:
Quinidine-prototype
procainamide
disopyramide
Class 1A agents are not commonly used because
they can cause toxicity that may precipitate heart failure
Disopyramide is an
oral agent, used to suppress atrial and ventricular tachyarrhythmias, and has significant myocardial depressant effects and can precipitate CHF and hypotension
Procainamide is used
in the treatment of ventricular tachyarrhythmias (less effective with atrial) class 1A drug
Side effects of procainamide include
myocardial depression leading to hypotension & syndrome that resembles lupus erythematous
The dosage of procainamide is
loading 100 mg IV every 5 minutes until rate controlled (max 15 mg/kg); then infusion 2-6 mg/min.
Class 1C agents include:
flecainide- Class 1C prototype
propafenone (oral)
Class 1C agents work by
slowing Na+ channel blocker (slow dissociation)
potent decrease of depolarization rate phase 0 and decreased conduction rate with increased AP
markedly inhibits conduction through the His-Purkinje system
Propafenone is used for (& how supplied)
suppression of ventricular and atrial tachyarrhythmias
has pro-arrhythmic side effects
oral agent
Flecainide is effective in the treatment of
suppressing ventricular PVCs and ventricular tachycardia, also atrial tachyarrhythmias; Wolff-Parkinson-White syndrome
- oral agent
- has pro-arrhythmic side effects
Class 1B agents include:
lidocaine-prototype
Mexiletine (oral)
Phenytoin
Class 1B agents work by
fast dissociation on fast Na+ channel blocker
alters the AP by inhibiting sodium influx via rapidly binding to and blocking sodium channels (fast)
shortens AP duration and shortens refractory period
decreases automaticity
Lidocaine is used in the treatment of
ventricular arrhythmias- no longer recommended for preventing ventricular fibrillation after acute MI
particularly effective in suppression reentry rhythms: ventricular tachycardia, fibrillation, PVCs
Dosage of lidocaine includes:
1-1.5 mg/kg IV; infusion 1-4 mg/min (mas dose 3 mg/kg)
Lidocaine is metabolized in
the liver and is 50% protein bound
has active metabolite which prolongs elimination half-time
Lidocaine is eliminated
10% renally
Lidocaine metabolism may be impaired by
drugs such as cimetidine and propranolol or physiological altering conditions such as CHF, acute MI, liver dysfunction
Lidocaine metabolism might be induced by
drugs like barbiturates, phenytoin, or rifampin
Adverse effects of lidocaine include
hypotension, bradycardia, seizures, CNS depression, drowsiness, dizziness, lightheadedness, tinnitus, confusion, apnea, myocardial depression, sinus arrest, heart block, ventilatory depression, cardiac arrest, and can augment preexisting neuromuscular blockade
Mexiletine is used for
1B drug used for chronic suppression of ventricular cardiac tachyarrhythmias
Phenytoin is used for
class 1B agent and is used in suppression of ventricular arrhythmias associated with digitalis toxicity can also be used for ventricular tachycardias or torsade de pointes
Phenytoin dose:
1.5 mg/kg IV every 5 min up to 10-15 mg/kg
can cause pain or thrombosis when given peripheral IV
can cause severe hypotension if given rapidly
Therapeutic blood levels of phenytoin include:
10-18 mcg/mL
toxicity causes CNS disturbances
Phenytoin metabolism and excretion
liver; excreted urine
Elimination half time of phenytoin is
24 hours
Adverse effects of phenytoin include
CNS disturbances, partially inhibits insulin secretion, bone marrow depression, nausea, associated with Steven Johnson’s syndrome
Class II drugs include
beta-adrenergic antagonists and they work by depressing spontaneous phase 4 depolarization resulting in SA node discharge
Class II drugs work by
slow speed of conduction of cardiac impulses through atrial tissues; decreased automaticity; drug-induced slowing of heart rate with decreases in myocardial oxygen requirements is desirable in patients with CAD
Class II agents include
propanolol- prototype
esmolol
Class II agents are used to treat
SVT, atrial and ventricular arrhythmias
used to suppress and treat ventricular dysrhythmias during MI and reperfusion
treat tachyarrhythmias secondary to digoxin toxicity and SVT (afib or aflutter)
Class II agents help with tachyarrhythmias because
they prevent catecholamine binding to beta receptors
slow heart rate
decrease myocardial oxygen requirements
Propranolol is a
beta-adrenergic antagonist (non-selective)
Propranolol is used to prevent
reoccurrence of tachyarrhythmias both supraventricular and ventricular precipitated by sympathetic stimulation
Cardiac effects of propranolol include
decreased HR, contractility, CO; increased PVR, coronary vascular resistance, and lowered oxygen demand
The onset, peak, and elimination half time of propranolol include
Onset: 2-5 minutes
Peak: 10-15 minutes, duration 3-4 hours
elimination half-time: 2-4 hours
Metoprolol is a
beta-adrenergic antagonist (selective B1)
The dose of metoprolol is
5 mg IV over 5 minutes; max dose 15 mg over 20 min.
The onset and half life of metoprolol is
onset: 2.5 min.
half-life: 3-4 hours
Metoprolol is metabolized
by the liver & can be used in mild CHF
Esmolol is a
beta-adrenergic antagonist (selective Beta 1)
effects HR without decreasing BP significantly
The dose of esmolol is
0.5 mg/kg IV bolus over 1 minute then 50-300 mcg/kg/min
The duration of esmolol is
<10 minutes
Esmolol is metabolized by
plasma esterases
Class III drugs work by
blocking potassium ion channels
work at phase III of cardiac cycle and extend repolarization, prolong depolarization, and increase action potential duration
Class III agents are used to treat
supraventricular and ventricular arrhythmias, and control rhythm in afib
prophylaxis in cardiac surgery patients related to high incidence of afib
preventative therapy in patients who have survived sudden cardiac death who are not candidates for ICD
Class III agents can cause
prolonged QT interval and torsades development
Class III agents include
amiodarone- class III prototype (can have thyroid dysfunction b/c contain iodine) dronedarone Ibutilide Dofetilide (oral) Sotalol
Amiodarone is a
class III antiarrhythmic drug with class I, II, and IV antiarrhythmic properties
Amiodarone works by
blocking potassium, sodium, and calcium, alpha and beta adrenergic antagonist
Amiodarone is used for
prophylaxis or acute treatment in the treatment of atrial and ventricular arrhythmias (refractory SVT, refractory VT/VF, AF)
1st line drug VT/VF when resistant to electrical defibrillation
Amiodarone dose is
bolus 150-300 mg IV over 2-5 minutes, up to 5 mg/kg then 1 mg/hr x 6 hours, then 0.5 mg/hr x 18 hours
Amiodarone half-life is
29 days
Amiodarone is metabolized
in the liver and has active metabolite (hence long half-life)
biliary/intestinal excretion
Therapeutic plasma levels of amiodarone are
1.0-3.5 micrograms/mL
Amiodarone protein binding is
96% and has large volume of distribution
Patients receiving amiodarone need to be
monitored for potassium increases because they are susceptible to torsades
Adverse effects of amiodarone include:
pulmonary toxicity, pulmonary edema, ARDs, photosensitive rashes, grey/blue discoloration of skin, thyroid abnormalities, corneal deposits, CNS/GI disturbance, pro=arrhythmic effects (torsades de pointes), heart block, hypotension, sleep disturbances, abnormal LFT (20%), inhibits hepatic CYP450 so might see prolonged effects of muscle relaxants, coumadin, or digoxin
Sotalol side effects
prolonged QT interval, bradycardia, myocardial depression, fatigue, dyspnea, AV block
Sotalol should be used in caution with
asthmatics
Sotalol is excreted in
the urine
Sotalol is used to treat
severe sustained ventricular tachycardia and ventricular fibrillation; to prevent reoccurrence of tachyarrhythmias especially aflutter and AF
Sotalol is a
Class II & class III antiarrhythmic drug beta-adrenergic antagonist (non-selective) and potassium channel blocker
Dofetilide and Ibutilide are
Class III antiarrhythmics and are used for conversion of afib or aflutter to NSR
used for maintenance of NSR after afib or conversion of afib to sinus
proarrhythmic
Class IV calcium channel blockers include
verapamil
diltiazem
nifedepine
Calcium channel blockers work by
binding to the receptor on voltage-gated calcium ions maintaining the channels in an inactive or closed state
Calcium ion channels are present in
cell membranes of skeletal muscle, vascular smooth muscle, cardiac muscle, mesenteric muscle, neurons, and glandular cells
Calcium channel blockers are classified based on
structure
phenyl-alkyl-amines-AV node (Verapamil)
benzothiazepines-AV node (diltiazem
1,4- dihydrophyridines-arterial beds (Nifedipine)
Calcium channel blockers work by
selectively interfering with inward calcium ion movement across myocardial and vascular smooth muscle cells
Calcium channel blocker uses include
Vascular- angina, systemic hypertension, pulmonary hypertension, cerebral arterial spasm, Raynaud’s disease, migraine
Non-vascular- bronchial asthma, esophageal spasm, dysmenorrhea, premature labor
Calcium channel blockers block
slow calcium channels and their primary site is the AV node during phase 2 (shortens phase 2)
contractility of the heart decreases
Calcium channel blockers have several subtypes
and the L type channel is important in determining vascular tone and cardiac contractility
Decreased Ca+ keeps intracellular Ca+ low
The effects of calcium channel blockers include
decreased contractility, decreased HR, decreased activity of SA node, decreased rate of conduction of impulses via AV node, vascular smooth muscle relaxation: decreased SVR & BP (arterial>venous)
Calcium channel blockers are used to treat
SVT, ventricular rate control in afib & aflutter, used to prevent reoccurrence of SVT
not used in ventricular arrhythmias
Calcium channel blockers include
verapamil- class IV prototype diltiazem
Clinical uses of verapamil include
SVT, vasospastic angina pectoris, HTN, hypertrophic cardiomyopathy, maternal and fetal tachydysrhythmias, premature onset of labor
Verapamil is a
class IV antiarrhythmic synthetic derivative of papaverine its levoisomer is specific for the slow calcium channel
The primary site of verapamil is the
AV node
it depresses the AV node, negative chronotropic effect on SA node, negative inotropic effect on myocardial muscle, moderate vasodilation on coronary as well as systemic arteries
Verapamil peak and half-life
oral: 30-45 minutes/IV 15 minutes
half life is 6-12 hours
Verapamil is highly
protein bound & the presence of other agents such as lidocaine, diazepam, propranolol increase its activity
Verapamil is (metabolism)
almost completely absorbed with extensive first pass metabolism and almost none of the drug appears unchanged in the urine
Verapamil dose is
2.5-10 mg IV over 1-3 minutes (max dose 20 minutes)
continuous infusion 5 mcg/kg/minute
Verapamil should not be given with
beta blockers as it leads to heart blocks
Verapamil half life is
6-8 hours
Verapamil is metabolized and excreted
metabolized in the liver with active metabolite
excreted in the urine and bile
Verapamil side effects are
myocardial depression, hypotension, constipation, bradycardia, nausea, prolongs effects of neuromuscular blockers
Diltiazem is a
calcium channel blocker and benzothiazepine derivative
Clinical uses of diltiazem include
similar to verapamil, SVT, vasospastic angina pectoris, HTN, hypertrophic cardiomyopathy, maternal and fetal tachydysrhythmias
Diltiazem administration:
PO or IV
Dose is 0.25-0.35 mg/kg over 2 minutes can repeat in 15 minutes
IV infusion 10 mg/hr
The principle site of action of diltiazem includes
the AV node
The 1st line of treatment for SVT is
diltiazem
Diltiazem has (potency)
intermediate potency between verapamil and nifedipine
also has minimal CV depressant effects
The onset of action, peak, and elimination half- life of diltiazem is
oral onset: 15 minutes
peaks: 30 minutes
elimination half-life of 4-6 hours
Diltiazem is excreted
in the bile and urine
also highly protein bound 70-80%
General side effects of calcium channel blockers include:
cancer, cardiac problems, bleeding, constipation
Nifedipine is a
dihydrophyridine derivative
calcium channel blocker
Clinical uses of nifedipine include
angina pectoris
The primary site of action of calcium channel blockers is
peripheral arterioles
has coronary and peripheral vasodilator properties > verapamil
Nifedipine can cause
reflex tachycardia due to decreased SVR & BP
can produce myocardial depression in patients with LV dysfunction or on beta blockers
has little to no effect on SA or AV node
Nifedipine can be administered
IV, oral, or sublingual
Nifedipine is metabolized
in the liver and excreted in the urine
90% protein bound
Drug interactions with calcium channel blockers include:
verapamil- increases risk of local anesthetic toxicity
beta blockers- can put someone into heart block
can potentiate neuromuscular blockers
can cause myocardial depression and vasodilation with inhalational agents
verapamil and dantrolene can cause hyperkalemia and can result in cardiac collapse
Toxicity of calcium channel blockers may be reversed
with IV administration of calcium or dopamine
Calcium channel blockers can interact with
calcium mediated platelet function
digoxin: CCBs can increase the plasma concentration of digoxin
H2 antagonists: ranitidine and cimetidine alter hepatic enzyme activity and thus could increase plasma levels of CCB
Side effects of calcium channel blockers include
vertigo, HA, flushing, hypotension, paresthesias, muscle weakness, can induce renal dysfunction, coronary vasospasm with abrupt discontinuation
_____ has the greatest coronary artery dilation among the calcium channel blockers
nicardipine
Adenosine works by
binding to A1 purine nucleotide receptors (activates adenosine receptors to open K+ channels and increase K+ currents)
slows AV nodal conduction
Adenosine is used for
termination of SVT/ diagnosis of VT
and to stop arrhythmia from occurring
The dose of adenosine is
6 mg IV rapid bolus
repeated if necessary after 3 minutes, 6-12 mg IV
The half-life of adenosine is
<10 seconds
Adenosine is eliminated by
plasma and vascular endothelial cell enzymes in RBCs
The side effects of adenosine include:
excessive AV or SA nodal inhibition, facial flushing, HA, dyspnea, chest discomfort, nausea, bronchospasm
contraindicated in asthma, heart block
Digoxin is a
cardiac glycoside
positive inotrope- used to treat CHF
Digoxin works by
increasing vagal activity and thus decreasing activity of SA node and prolongs conduction of impulses thru the AV node
decreases HR, preload, and afterload
slows AV conduction by increasing AV node refractory period
Digoxin is used for the management of
atrial fibrillation or flutter (controls ventricular rate), especially with impaired heart function
Digoxin dose is
0.5-1 mg in divided doses over 12-24 hours
The onset of action of digoxin is
30-60 minutes
The half time of digoxin is
36 hours
Digoxin dosing needs to be reduced in
elderly & renal impairment
Digoxin is excreted
by the kidneys
Digoxin has a narrow
therapeutic index
0.5-1.2 ng/mL
need to check levels
Magnesium works by
working at sodium, potassium, and calcium channels
Magnesium can be used for
torsades de pointes
Magnesium dose is
1 gm IV over 20 minutes and can be repeated
The adverse effects of digoxin include
arrhythmias, heart block, anorexia, nausea, diarrhea, confusion, agitation
potentiated by hypokalemia and hypomagnesaemia
The toxicity treatment for digoxin includes
phenytoin for ventricular arrhythmias, pacing, and atropine
