Antiarrhythmics Flashcards
arrythmia
-abnormal origin
-rhythm or rate of heartbeats
-occur as result of disturbances in cardiac impulse formation or conduction
-supraventricular- in the atrium, AV node
-ventricular- ventricle
-tachyarrhythmias
-bradyarrhythmias
when is tx required for arrythmia
-some benign- do not require tx
-some meds are worse off for pt then the arrhythmia
normal heart beat
-originates in SA node in RA -> AV node -> bundle of his -> left and right bundle branches -> purkinje fibers -> ventricles
-when to treat:
-decrease in CO
-BP
causes of arrhythmia
-Coronary ischemia
-Tissue hypoxia
-Electrolyte disturbances - K
-Over stimulation of SNS
-General anesthetics
-Any other condition or drug that may affect cardiac transmembrane potentials and lead to abnormal impulse formation or conduction
abnormal impulse formation
-increased automaticity
-afterdepolarizations
increased automaticity
-caused by any change that causes the tissues to depolarize more rapidly and thereby generate abnormal impulses
-decrease in the time required for depolarization from the maximum diastolic potential to the threshold potential
afterdepoliarzations
-abnormal impulses resulting from spontaneous generation of action potentials during or immediately after phase 3 repolarization
-early” vs “late” –
-Causes –
abnormal impulse conduction
-formation of arrhythmia by the process of reentry, a process that involves reexcitation of a particular zone of cardiac tissue by the same impulse
-1. Reentry in ventricular tissue
-2. reentry in AV node
drug induced arrhythmias: sympathomimetics
-increase automaticity of SA node, AV node or his-purkinje fibers
drug-induced arrhythmias: digitalis glycosides
-cause afterdepolarizations by increasing Ca influx into cardiac cells
-also impair AV node conduction and can cause AV block
drug-induced arrhythmias: torsade de pointes ventricular tachycardia
slow ventricular repolarization and QT prolongation. Caused by certain antiarrhythmic drugs, psychotropic drugs, antibiotics and other miscellaneous drugs like cisapride
non pharm therapy for arrythmias
-1. Cardiac ablation (interrupts reentry circuits)
-2. Implantable cardioverter-defibrillator (ICD) – good survival data in trials. Prevents primary and secondary sudden cardiac death
Mechanisms and Classifications of Antiarrhythmic drugs (Vaughan- Williams)
-type 1/class1 -> type 1a, type 1b, type 1c
-type 2/class 2- beta-adrenergic receptor blockers -> Decrease slope of phase 4
-type 3/class 3- K channel blockers or other drugs which prolong action potential duration -> Prolong phase 3
**Amiodarone also affects phase 1,2 & 4
-type 4/class 4- Calcium Channel Blockers -> Prolongs phase 2
-type 5/class 5- Miscellaneous
cardiac cell action potential
affects of Ca and QT
-decrease Ca, increase QT- torsades de pointes
-increase Ca, decrease QT- toxicity due to digoxin
type 1/class 1
-largest group
-Na channel blockers
-MOA – bind to Na channels when they are open and inactivated, dissociate from the channel during the resting state
-More pronounced effect on cardiac tissue that is rapidly firing*
-further subdivided based on affinity for open state or inactivated state and based on their rate of dissociation from the Na channels
-1A,1B,1C IS NOT ON TEST:
-1. Type 1A – greater affinity for open state with slow recovery
-Depress PHASE 0, prolonging repolarization
-2. Type 1B – greater affinity for inactivated state and slow recovery
-More pronounced effect on ischemic tissue
-Depress PHASE 0 selectively in abnormal/ischemic tissue, shorten repolarization
-3. Type 1C – greater affinity for open state and very slow recovery
-Greater effect on ventricular conduction
-Markedly depress PHASE 0, minimal effect on repolarization
type 1A drugs
-MOA – block Na+ channel and K+ channel**
-Suppress abnormal automaticity but do not significantly affect SA node automaticity and HR
-All have some antimuscarinic (atropine-like) activity and may inhibit PNS effects on SA node and AV node
-Depress phase 0, prolonging repolarization
-act on fast channels
-quinidine
-procainamide
-disopyramide
-these were the first but arnt really used anymore
quinidine
-Available as gluconate or sulfate salt
-NOTE 267 mg quinidine gluconate = 200mg of quinidine sulfate (dont need to know)
-Indications – TX most types of supraventricular and ventricular arrhythmias
-ADRs – hypotension, GI effects (diarrhea 30-40%), thrombocytopenia, CINCHONISM (ASA toxicity - tinnitus, blurred vision, dizziness) headache, confusion, torsades de pointes
-DDI – CYP450 substrate and inhibitor. Several interactions
procainamide
-Amide derivative of local anesthetic procaine
-Absorbed from gut and converted to active metabolite N-acetylprocainamide (NAPA)
-Indications - Tx most types of supraventricular and ventricular arrhythmias. Produces less hypotension than quinidine IV – so more often used IV for TX of acute ventricular arrhythmias.
-ADRs – hypotension, GI effects, CNS effects, hematologic (thrombocytopenia), anticholinergic effects, liver toxicity, lupus-like syndrome (50%)**
-DDI – CYP2D6 substrate
-less issues with hypotension than quinindine
torsades tx
magnesium
disopyramide
-Indications - Used for atrial fibrillation or ventricular arrhythmias
-Use with caution in pts with CHF and elderly
-ADRs – hypotension, anticholinergic effects (blurred vision, urinary retention), CHF, CNS effects including hallucinations.
-DDI – CYP3A4 substrate
type 1B drugs MOA
-Electrophysiological properties make them particularly suitable for ventricular arrhythmias*
-Strong affinity for Na channels in depolarized ischemic tissue, but lack of effect on Na channels in normal cardiac tissue. Depress phase 0 selectively in abnormal/ischemic tissue, shorten repolarization
-lidocaine
-mexilitine
lidocaine
-Also a local anesthetic
-Extensive first pass hepatic inactivation after PO, therefore must be given IV
-Indications – Ventricular tachycardia and other acute ventricular arrhythmias. Not useful for supraventricular arrhythmias.
-ADRs – CVS (bradycardia, hypotension, heart block), CNS (drowsiness, paresthesias, disorientation, muscle twitching- may lead to seizures)
-May also cause psychosis* and respiratory depression -> peds seizures
-effective for ischemic tissue- not used for SVT
mexilitine and tocainide
-Do not undergo first pass effect, therefore used PO
-Indications – long-term basis for suppression of ventricular arrhythmias
-good bridging drug from iv to oral
-ADRs – GI and CNS effects, Agranulocytosis with tocainide
type IC drugs
-block Na+ channels and block the rate of rise of the action potential during phase 0 to a greater extent than other class I drugs. They slow conduction velocity throughout the heart and especially in His-Purkinje system.
-Markedly depress phase 0, minimal effect on repolarization
-flecainide
-propafenone
flecainide
-Indications – Treatment of supraventricular arrhythmias and documented life threatening ventricular arrhythmias
-ADRs – reentry ventricular tachycardia, CHF, GI, CNS, blurred vision
-DDI – CYP450 substrate, CYP2DR inhibitor
propafenone
-Similar effects as flecainide except less effects on QT interval. Also has some beta blocking activity.
-Indications – same as flecainide
-ADRs - same as flecainide but also hematological SEs
-DDI – CYP450 substrate, CYP1A2, 2D6 inhibitor
moricizine
-Unusual properties, so may not be assigned to subgroup by some reference sources. Phenothiazine analogue. Similar MOA to flecainide
-Indications – documented life-threatening ventricular arrhythmias. (Long term use may be associated with increased mortality rate in pts with history of MI)
type 2/class 2 drugs
-inhibits SNS activation of cardiac automaticity and conduction
-Slow heart rate, decrease AV node conduction velocity and increase AV node refractory period
-Indications: Used for prevention and treatment of supraventricular arrhythmias and for their ability to reduce ventricular ectopic depolarizations and sudden death in pts with myocardial infarction
-beta blockers
-esmolol
-metoprolol
-acebutolol
esmolol
-IV, rapidly metabolized, short half life
-Used to treat acute SVT*
metoprolol and propranolol
-Both available PO or INJ for treatment and suppression of supraventricular and ventricular arrhythmias*
-Metoprolol – given IV in early phase of MI followed by PO – protects the heart against the damage caused by ischemia and free radicals that may be formed during reperfusion of coronary arteries when fibrinolytics are used
acebutolol
-category B in 2nd and D in 3rd trimester
-used for ventricular arrhythmias*
type 3/class 3
-block K+ channels and prolong the ventricular action potential depolarization and refractory period
-all of these drugs can potentially cause torsades
-amiodarone**
-dronedarone
-ibutilide
-sotalol
-dofetilide
-bretylium
amiodarone***
-Properties – organic iodine compound similar to thyroid hormones. Unusual kinetics, very long half -life (40 days)
-affects every phase except 0
-MOA – Type III, but also blocks Na channels, Ca channels and beta-adrenergic receptors.
-Decreases SA node automaticity, decreases AV node conduction velocity and prolongs AV node and ventricular refractory periods.
-Indications – PO for supraventricular and ventricular arrhythmias incl AF, atrial flutter, SVT and life threatening ventricular tachycardia. IV for acute life-threatening VF or sustained VT
-ADRs – Several. GI effects, CV effects (hypotension, AV block, arrhythmias incl torsades (less torsades than other Class III agents), visual disturbances, thyroid dysfunction**, pulmonary fibrosis and pneumonitis, blue-gray skin discoloration
-DDI – CYP450 substrate and inhibitor of almost all isoenzymes. Several DDI which increase levels of other important drugs like digoxin, phenytoin, warfarin
dronedarone
-newer drug
-Properties – structurally similar to amiodarone but with shorter half-life, less lipophilicity and no iodine group so les risk of thyroid, pulmonary and neurological side effects
-MOA – like amiodarone. Exhibits MOA of all Vaughan-Williams classifications
-Indications – to reduce risk of CV hospitalization in patients with Afib or Aflutter with certain CV risk factors
-ADRS – Like amiodarone but w/ less thyroid, pulmonary and neurological (visual) ADRs
-DDIs – several CYP450 DDIs esp w digoxin, CCBs and warfarin
ibutilide
-MOA - Different MOA than other Type III drugs. Promotes influx of Na+ through slow inward Na channels which counteracts the outward K+ current thereby prolonging repolarization
-Indications – Rapid conversion of AF or atrial flutter
-ADRs – torsades de pointes
sotalol
-MOA – nonselective beta-blocker with ability to block K+ current during ventricular action potential.
-Indications – ventricular arrhythmias, AF (avoid in HF)
-ADRs – dose dependent torsades de pointes, hypotension, bradycardia, bronchospasm
dofetilide
-MOA – basic Type III mechanism - blocks K channel
-Indications – chronic AF and atrial flutter
-ADRs – dose dependent torsades de pointes, CNS effects
bretylium
-MOA – prolongs ventricular action potential in normal tissue more than ischemic tissue
-inpatient
-Indications – VF
-ADRs – GI effects, orthostatic hypotension, CNS effects
type 4 drugs
-Calcium channel blockers (non-DHP)
-(there are also DHP calcium channel blockers)
-MOA – decrease AV node conduction velocity and increase AV node refractory period (blocks Ca+ from entering slow channels during depolarization)
-Indications – IV for acute PSVT, PO for AF (avoid if coexisting HF)
-ADR- constipation
-Examples – Diltiazem and Verapamil
type 5: miscellaneous
-adenosine
-digoxin
-magnesium sulfate
adenosine (IV)
-MOA – activates specific G protein-coupled adenosine receptors resulting in hyperpolarization and slowing of AV node conduction velocity
-Indications – SVT, PSVT (preferred drug for PSVT)**
-ADRs – flushing, dizziness, bradycardia, syncope
digoxin (IV)
-MOA – increases vagal tone, slows AV node conduction velocity and increases AV node refractory period
-Indications – AF, PSVT
-ADRs – GI, CNS, arrhythmias (treat the arrhythmia w/ lidocaine)
magnesium sulfate (IV)
-MOA – slows rate of SA node impulse formation and prolongs conduction time
-Indications – VT, VF and torsades de pointes*
-ADRs – GI (diarrhea)*, CNS depression, flushing (dose dependent)
afib: most common arrhythmia
-Present in 2.2 million Americans
-Prevalence increases w/ age
-Occurs commonly in pts w/ HF and valvular heart disease
-irregularly irregular
-no P waves
-disorganized atrial activity
management of afib: rate control vs rhythm control
-FIRST - Control rate primarily w/ BBs, CCBs or digoxin
-Rhythm control (may not be necessary):
-Electrical cardioversion
-Cardiac ablation
-Pharmacological cardioversion w/ Class I or Class III antiarrhythmics (CHOICE DEPENDS ON PMH)**
-Combo therapy (cardioversion + drug therapy)
-Risk of stroke does exist w/ cardioverson:
-Assure adequate anticoagulation for 3 weeks prior to cardioversion OR
-Perform TEE to check for thrombi
therapy and stroke rate/year
newer oral anticoagulants with afib indication
-Dabigatran (Pradaxa)
-Rivaroxaban (Xarelto)
-Apixaban (Eliquis)
risk factors for afib induced stroke (CHADS2 score)
-CHF = 1 point
-HTN = 1 point
-Age > 75 = 1 pt
-DM = 1 pt
-Previous stroke = 2 pt
JD is a 76 year-old male with a h/o of HTN and DM who is referred to the Anticoagulation Clinic for anticoagulation initiation and follow-up when a new diagnosis of atrial fibrillation was made. He is to be scheduled for cardioversion after proper anticoagulation. The patient’s current medications include lisinopril 10 mg po daily, HCTZ 25 mg po daily and metformin 500 mg po bid.
-CHAD- 3
-5.3 risk
-warfarin -> must check INR 2-3
-NOAC- novel oral anticoagulation/DOAC- direct oral anticoagulation (same thing)
AMIODARONE
-class 3
-thyroid disease, pulmonary fibrosis, skin discoloration, visual disturbances, risk for other arrythmias (QT), hypotension
-TFTs, BP, LFTs, DDI
-30 tablets prescription
