A Practical Overview of Antiarrhythmic Drugs Commonly Used in Atrial Fibrillation RESOURCE SESSION A...
Transcript of A Practical Overview of Antiarrhythmic Drugs Commonly Used in Atrial Fibrillation RESOURCE SESSION A...
A Practical Overview of A Practical Overview of Antiarrhythmic Drugs Commonly Antiarrhythmic Drugs Commonly
Used in Atrial FibrillationUsed in Atrial Fibrillation
RESOURCE SESSIONRESOURCE SESSION
Olavo Fernandes, Pharm.D. Olavo Fernandes, Pharm.D.
Pharmacy Practice Leader, Pharmacy Practice Leader, Toronto General Hospital, UHNToronto General Hospital, UHN
Assistant Professor, University of TorontoAssistant Professor, University of Toronto
October 2002October 2002
Cardiac Conduction SystemCardiac Conduction System
SA nodeSA node– primary pacemaker (60-100 primary pacemaker (60-100
bpm)bpm)– autonomic nervous systemautonomic nervous system– vagus nerve (parasym.)vagus nerve (parasym.)– catacholamines (sym)catacholamines (sym)
AV nodeAV node– filter (40-60 bpm)filter (40-60 bpm)– controls number of controls number of
impulses reaching the impulses reaching the ventricle from atriaventricle from atria
Bundle of HisBundle of His– conducts impulses to conducts impulses to
bundle branchesbundle branches
Perkinje systemPerkinje system– < 40 bpm< 40 bpm– bifarcates into several bifarcates into several
bundle brunches bundle brunches
Electrocardiogram (ECG)Electrocardiogram (ECG)
P waveP wave– depolarization of atriadepolarization of atria
QRS ComplexQRS Complex– depolarization of ventricledepolarization of ventricle
– QRS interval normally < 0.12 QRS interval normally < 0.12 secs.secs.
– widened QRS: prolonged widened QRS: prolonged conductionconduction
– QRS > 0.12 secs: QRS > 0.12 secs: conduction from ventricle or conduction from ventricle or supraventricularsupraventricular
T waveT wave– repolarization of ventriclerepolarization of ventricle
U waveU wave– uncertainuncertain
PR intervalPR interval– < 0.2 seconds< 0.2 seconds– conduction velocityconduction velocity– beginning of P wave to onset of beginning of P wave to onset of
QRSQRS
QTQTcc interval interval– < 0.4 seconds< 0.4 seconds– refractory periodrefractory period– beginning of Q to end of Tbeginning of Q to end of T
Cardiac Action PotentialsCardiac Action Potentials
Sodium-dependent Fibres/ Fast FibresSodium-dependent Fibres/ Fast Fibres– atrial and ventricular tissueatrial and ventricular tissue– Phase O, 1, 2, 3, 4Phase O, 1, 2, 3, 4
Calcium-dependent FibresCalcium-dependent Fibres– SA and AV nodesSA and AV nodes– only 3 phasesonly 3 phases– Ca enters instead of Na in Phase OCa enters instead of Na in Phase O– higher resting membrane potentialhigher resting membrane potential– increase in slope of phase 4increase in slope of phase 4
Refractory PeriodRefractory Period
AutomaticityAutomaticity– intrinsic property of spontaneous impulse generationintrinsic property of spontaneous impulse generation
ClassificationClassification (Circulation 2001; 104: 2118-2150)(Circulation 2001; 104: 2118-2150)
Atrial ArrhythmiasAtrial Arrhythmias
Goals of TherapyGoals of Therapy convert to sinus rhythmconvert to sinus rhythm control ventricular response ratecontrol ventricular response rate relieve associated symptoms (palpitations, relieve associated symptoms (palpitations,
fatigue, dyspnea, syncope, angina, heart fatigue, dyspnea, syncope, angina, heart failure)failure)
prevent recurrenceprevent recurrence prevent complications: life threatening prevent complications: life threatening
arrhythmias, stroke, MI, tachycardiaarrhythmias, stroke, MI, tachycardia
Atrial Fibrillation- Rate ControlAtrial Fibrillation- Rate Control
Why use an agent for rate control?Why use an agent for rate control?» better filling time, better diastolic functionbetter filling time, better diastolic function» consider risks of conversion, embolic risks, drug side effectsconsider risks of conversion, embolic risks, drug side effects
OPTIONSOPTIONS– DigoxinDigoxin
» increase vagal tone (decrease AV node conduction), inhibit Na/K increase vagal tone (decrease AV node conduction), inhibit Na/K PumpPump
– Beta Blockers ( metoprolol, esmolol, atenolol)Beta Blockers ( metoprolol, esmolol, atenolol)» slow SA node, slow AV node conduction, effect on refractory slow SA node, slow AV node conduction, effect on refractory
periodperiod
– Calcium Channel Blockers (diltiazem, verapamil)Calcium Channel Blockers (diltiazem, verapamil)» block slow calcium channels, slow AV node conductionblock slow calcium channels, slow AV node conduction
Rate Control Agent Rate Control Agent ConsiderationsConsiderationsDIGOXINDIGOXIN
– vagally mediatedvagally mediated– slow onset- 4hrs (large slow onset- 4hrs (large
VD)VD)– poor effectiveness poor effectiveness
during high sympathetic during high sympathetic tone (stress)tone (stress)
– positive inotrope (benefit positive inotrope (benefit with concurrent CHF)with concurrent CHF)
– proarrhythmic, side proarrhythmic, side effectseffects
Rate Control Agent Rate Control Agent ConsiderationsConsiderations
BETA BLOCKERSBETA BLOCKERS– faster onset (minutes)faster onset (minutes)
– directly effect on AV node directly effect on AV node (effective during stress)(effective during stress)
– negative inotrope (concern negative inotrope (concern in in CHF)CHF)
– may be useful with may be useful with concurrent CAD/Post MI concurrent CAD/Post MI patientspatients
– bronchospasm (asthma)bronchospasm (asthma)
– effect on blood sugar (DM)effect on blood sugar (DM)
– main SE: hypotensionmain SE: hypotension
CALCIUM CHANNEL CALCIUM CHANNEL BLOCKERSBLOCKERS– faster onset (minutes)faster onset (minutes)– directly effect on AV node directly effect on AV node
(effective during stress)(effective during stress)– negative inotrope (concern in negative inotrope (concern in
CHF) verapamil > diltiazemCHF) verapamil > diltiazem– may be useful with may be useful with
concurrent CAD/Post MI concurrent CAD/Post MI patientspatients
– main side effect:hypotensionmain side effect:hypotension– cost diltiazem > verapamilcost diltiazem > verapamil
Conversion of Atrial Conversion of Atrial FibrillationFibrillation ConsiderationsConsiderations
– better cardiac function, more times in A Fib harder to convert to NSR, better cardiac function, more times in A Fib harder to convert to NSR, emboli and anticoagulation, may need rate control during conversionemboli and anticoagulation, may need rate control during conversion
Direct Current ConversionDirect Current Conversion– 100J, 200J, 300J, 360J 100J, 200J, 300J, 360J – burns, relapse, sedation, worsened arrhythmiasburns, relapse, sedation, worsened arrhythmias
Pharmacological OptionsPharmacological Options– Amiodarone (least proarrhythmic, some AVN block, least negative Amiodarone (least proarrhythmic, some AVN block, least negative
inotropy, very costly IV)inotropy, very costly IV)– Procainamide, SotalolProcainamide, Sotalol– QuinidineQuinidine– IbutilideIbutilide
Management of newly discovered AFManagement of newly discovered AF(Circulation 2001; 104: 2118-2150)(Circulation 2001; 104: 2118-2150)
Pharmacologic cardioversion of AF<7 daysPharmacologic cardioversion of AF<7 days (Circulation 2001; 104: 2118-2150) (Circulation 2001; 104: 2118-2150)
Pharmacologic cardioversion of AF>7 daysPharmacologic cardioversion of AF>7 days(Circulation 2001; 104: 2118-2150(Circulation 2001; 104: 2118-2150
Pharmacological management of patients with Pharmacological management of patients with recurrent AF recurrent AF (Circulation 2001;1104: 2118-2150) (Circulation 2001;1104: 2118-2150)
Anticoa gula tion a nd ra te contro la s needed
Minim a l or no sym ptom s
D isopyra m ideProca ina m ide
Q uinid ine
non pclg
Am ioda rone
Fleca inidePropa fenone
Sota lo l
N o (or m inim a l)*
Am ioda rone
H F
D isoprya m ideProca ina m ide
Q uinid ine
Am ioda rone
Sota lo l
C AD
Am ioda rone
Yes
D isoprya m ideProca ina m ide
Q uinid ine
Am ioda roneSota lo l
F leca inidePropa fenone
N o
LVH >1.4 cm
H ypertension
Yes
H ea rt D isea se
Anticoa gula tion a nd ra te contro l a s needed
D isa bling sym ptom s
R ecurrent pa roxysm a lAF
Drug Profile: DigoxinDrug Profile: Digoxin MechanismMechanism
– binds and inhibits Na/K binds and inhibits Na/K ATPaseATPase
– slows AV node conduction slows AV node conduction (vagus nerve)(vagus nerve)
KineticsKinetics– dist: wide 7-8 L/kg (skeletal dist: wide 7-8 L/kg (skeletal
muscle, myocardium, kidneys)muscle, myocardium, kidneys)– ptn binding : 20-40%ptn binding : 20-40%– elimination: renal 70-80%; elimination: renal 70-80%;
hepatic (up to 30%)hepatic (up to 30%)– time to peak: 1-4 hr (IV); 2-6 hr time to peak: 1-4 hr (IV); 2-6 hr
(po)(po)
– time to steady state: 5-7 days time to steady state: 5-7 days (2-3 wks in RF)(2-3 wks in RF)
– elimination half life: 35-40 hrs elimination half life: 35-40 hrs (2-5 days in RF)(2-5 days in RF)
IndicationsIndications– CHF, AF- rate controlCHF, AF- rate control
DosingDosing– load: 0.250mg IV over 15 min load: 0.250mg IV over 15 min
repeat in 6hr; 0.250 mg po q6h repeat in 6hr; 0.250 mg po q6h x 4 (total 1 mg)x 4 (total 1 mg)
– renal dysfunction load 0.125mg renal dysfunction load 0.125mg q6h (total 0.5-0.75 mg)q6h (total 0.5-0.75 mg)
– initial mx dose: 0.125 - 0.250 initial mx dose: 0.125 - 0.250 mg pomg po
Drug Profile: DigoxinDrug Profile: Digoxin Adverse EffectsAdverse Effects
– GIGI: N, V, A, D: N, V, A, D– CNS:CNS: disorientation, confusion disorientation, confusion– Ocular:Ocular: colour vision colour vision
disturbances (yellow-green), disturbances (yellow-green), halos, photophobiahalos, photophobia
– CV:CV: bradycardia, heart block, bradycardia, heart block, VTVT
– more prone to toxicity with more prone to toxicity with hypokalemia (sensitizes hypokalemia (sensitizes myocardium to digoxin effect)myocardium to digoxin effect)
– toxicity: hyperkalemia, toxicity: hyperkalemia, ventricular arrhythmias, visual ventricular arrhythmias, visual disturbancesdisturbances
– DIGIBINDDIGIBIND
Drug InteractionsDrug Interactions– physically adsorption physically adsorption
(antacids, sucralfate, resins)(antacids, sucralfate, resins)
– antibiotics (digoxin antibiotics (digoxin metabolized by gut bacteria)metabolized by gut bacteria)
– increased serum level increased serum level (quinidine, amiodarone, (quinidine, amiodarone, verapamil)verapamil)
– assay interference assay interference (spironolactone)(spironolactone)
MonitoringMonitoring– ECG, HR, renal function, ECG, HR, renal function,
potassium, digoxin levelspotassium, digoxin levels
Digoxin: serum levelsDigoxin: serum levels Therapeutic RangeTherapeutic Range
– 1.2- 2.5 nmol/L 1.2- 2.5 nmol/L – AFib at higher end of targetAFib at higher end of target
Indications Indications – suspected toxicity/ suspected toxicity/
confirmationconfirmation– initiation or change in therapyinitiation or change in therapy– changes in renal functionchanges in renal function– clinical deteriorationclinical deterioration– addition of interacting addition of interacting
medicationsmedications– routine monitoring - yearlyroutine monitoring - yearly– subtherapeutic responsesubtherapeutic response
Sample Collection TimeSample Collection Time– not < 8 hrs and preferably not < 8 hrs and preferably
trough level before next dosetrough level before next dose– at least 5 days after starting tx at least 5 days after starting tx
or changing doseor changing dose– Increased levelsIncreased levels
Increased LevelsIncreased Levels– advanced age, renal disease, advanced age, renal disease,
hepatic disease, amiodarone, hepatic disease, amiodarone, verapamil, CsA, quinidineverapamil, CsA, quinidine
Decreased levelsDecreased levels– hyperthyroidism, binding drug hyperthyroidism, binding drug
interactionsinteractions
Drug Profile: DigoxinDrug Profile: Digoxin
ADVANTAGESADVANTAGES Positive inotropePositive inotrope Maybe useful in Maybe useful in
patients with patients with concurrent AF / CHFconcurrent AF / CHF
LIMITATIONSLIMITATIONS Limited to atrial Limited to atrial
arrhythmiasarrhythmias Limited efficacyLimited efficacy Pro-arrhythmicPro-arrhythmic Narrow therapeutic rangeNarrow therapeutic range Limited efficacy during Limited efficacy during
high sympathetic tonehigh sympathetic tone Caution with adverse Caution with adverse
effects/ drug interactionseffects/ drug interactions
Drug Profile: DiltiazemDrug Profile: Diltiazem Mechanism:Mechanism:
– blocks slow calcium channelsblocks slow calcium channels– slows AV node conductionslows AV node conduction– vasodilatationvasodilatation
Administration/DosingAdministration/Dosing– bolus and continuous infusionbolus and continuous infusion– 0.25 mg/kg over 2 minutes, 0.25 mg/kg over 2 minutes,
after 15 minutes can give 0.35 after 15 minutes can give 0.35 mg/kg over 2 minutesmg/kg over 2 minutes
– continuous infusion 10mg/hr continuous infusion 10mg/hr (up to 15mg/hr) x 24 hr(up to 15mg/hr) x 24 hr
– D5W, NSS, 2/3-1/3D5W, NSS, 2/3-1/3– refrigerated for storagerefrigerated for storage
Adverse Effects Adverse Effects – IV: hypotension, bradycardiaIV: hypotension, bradycardia– worsening CHF symptomsworsening CHF symptoms– heart blockheart block
Drug InteractionsDrug Interactions– AV node blocking agents (BB, AV node blocking agents (BB,
CCB, digoxin)CCB, digoxin)– hypotensive agentshypotensive agents– negative inotropesnegative inotropes
MonitorMonitor– ECG, BP, HRECG, BP, HR– CHF symptomsCHF symptoms
Drug Profile: MetoprololDrug Profile: Metoprolol Mechanism:Mechanism:
– competitive block agonist competitive block agonist effect of sympathetic effect of sympathetic neurotransmitters neurotransmitters
– block adrenergic stimulation block adrenergic stimulation of cardiac action potentialsof cardiac action potentials
– Beta-1 selective agentBeta-1 selective agent– slows AV node conductionslows AV node conduction
Administration/DosingAdministration/Dosing– 12.5 - 100 mg po bid12.5 - 100 mg po bid– 5mg IV push for acute 5mg IV push for acute
management ( if necessary management ( if necessary 10-15 mg IV q 6h)10-15 mg IV q 6h)
Adverse Effects Adverse Effects – IV: hypotension, bradycardiaIV: hypotension, bradycardia– worsening CHF symptomsworsening CHF symptoms– bronchospasm in asthmabronchospasm in asthma– heart blockheart block
Drug InteractionsDrug Interactions– AV node blocking agents AV node blocking agents
( CCB, digoxin)( CCB, digoxin)– hypotensive agentshypotensive agents– negative inotropesnegative inotropes
MonitorMonitor– ECG, BP, HRECG, BP, HR– CHF symptomsCHF symptoms
Drug Profile: AmiodaroneDrug Profile: Amiodarone Mechanism:Mechanism:
– complex pcl profile: actions of complex pcl profile: actions of all classes all classes
– conduction slowing (class I)conduction slowing (class I)– BB activity (class II)BB activity (class II)– prolong APD and refractory prolong APD and refractory
period (class III)period (class III)– AVN conduction slowing (IV)AVN conduction slowing (IV)– blocks cellular K channelsblocks cellular K channels
KineticsKinetics– bioavailability: 35-65%bioavailability: 35-65%– half life: mean 52 dayshalf life: mean 52 days– volume of distribution: 5000Lvolume of distribution: 5000L
– elimination: primarily elimination: primarily hepatic metabolism / biliary hepatic metabolism / biliary excretionexcretion
– active metabolite: desethyl-active metabolite: desethyl-amiodaroneamiodarone
Kinetic ImplicationsKinetic Implications» loading dosesloading doses» delayed AA effectdelayed AA effect» delayed elimination if drug delayed elimination if drug
stoppedstopped» compliancecompliance» role of levelsrole of levels
Drug Profile: AmiodaroneDrug Profile: Amiodarone
IndicationsIndications IVIV
– suppression of recurrent suppression of recurrent sustained VT, ongoing sustained VT, ongoing VT/VF, acute conversion of VT/VF, acute conversion of AFAF
Atrial Fibrillation/FlutterAtrial Fibrillation/Flutter– slow VRR (AVN block)slow VRR (AVN block)– convert to NSRconvert to NSR– maintain NSR after maintain NSR after
conversionconversion– dose lower in atrial dose lower in atrial
arrhythmiasarrhythmias
Post MIPost MI– CAMIAT and EMIATCAMIAT and EMIAT– showed amio. - low incidence showed amio. - low incidence
of proarrhythmia; safe in LV of proarrhythmia; safe in LV dysfunctiondysfunction
Primary prevention of SCDPrimary prevention of SCD– RFs for SCD: LV dysfunction, RFs for SCD: LV dysfunction,
frequent or complex ectopicsfrequent or complex ectopics– GESICSA and CHF STATGESICSA and CHF STAT– MADIT (ICD)MADIT (ICD)
Secondary prevention -SCDSecondary prevention -SCD– CASCADE, AVIDCASCADE, AVID– ICD preferredICD preferred– amio. second line amio. second line
Drug Profile: AmiodaroneDrug Profile: Amiodarone Administration/DosingAdministration/Dosing
– 150-300 mg IV over 10 minutes 150-300 mg IV over 10 minutes followed by 0.5 - 2 mg/kg followed by 0.5 - 2 mg/kg minute infusion (1000mg / 24 minute infusion (1000mg / 24 hrs)hrs)
– See handoutSee handout– continue oral load over several continue oral load over several
weeksweeks– Ventricular arrhythmiasVentricular arrhythmias
» 1200-1800 mg/d x 1-2 wks; 1200-1800 mg/d x 1-2 wks; 800mg/d x 2 wks; 600mg/d x 4 800mg/d x 2 wks; 600mg/d x 4 wks; then 200-400mg/dwks; then 200-400mg/d
– Atrial arrhythmiasAtrial arrhythmias» 600-800 mg/d x 4wks; 400 mg/d 600-800 mg/d x 4wks; 400 mg/d
x 2-4 wks; 200 mg/d thereafterx 2-4 wks; 200 mg/d thereafter
Adverse Effects (IV)Adverse Effects (IV)– hypotension (related to hypotension (related to
vehicle)vehicle)– peripheral vein phlebitis (run peripheral vein phlebitis (run
at < 2mg/ml)at < 2mg/ml)– IV infusions > 2 hrs IV infusions > 2 hrs
administer in glass bottles of administer in glass bottles of D5WD5W
– proarrhythmia : rareproarrhythmia : rare– 100% liver metabolism100% liver metabolism
MonitorMonitor– vitals, ECG, BP, HRvitals, ECG, BP, HR– vein site for phlebitisvein site for phlebitis
Amiodarone :Adverse EffectsAmiodarone :Adverse Effects Long term oral therapyLong term oral therapy
– 80% report side effects, in trials 80% report side effects, in trials only 10-20% have side effects only 10-20% have side effects necessitating withdrawalnecessitating withdrawal
– SE appear to be dose relatedSE appear to be dose related– minimize doses/ reduce dose is sx minimize doses/ reduce dose is sx
occuroccur– regular monitoring in preventing regular monitoring in preventing
and managing SEsand managing SEs
CVCV– sinus bradycardia (0-10%), AV sinus bradycardia (0-10%), AV
conduction disturbances and heart conduction disturbances and heart block (2-5%), rare TdPblock (2-5%), rare TdP
– increase plasma cholesterolincrease plasma cholesterol
PulmonaryPulmonary– most feared adverse effectmost feared adverse effect
– pulmonary fibrosis (2-7%) pulmonary fibrosis (2-7%) can be fatal in 10% of casescan be fatal in 10% of cases
– appears in pts with > 400mg/ appears in pts with > 400mg/ dayday
– CXR: bilateral and diffuse CXR: bilateral and diffuse changes/ interstitial infiltrateschanges/ interstitial infiltrates
– Sx: dyspnea, cough, chest Sx: dyspnea, cough, chest pain, pleural rubpain, pleural rub
Amiodarone : Adverse EffectsAmiodarone : Adverse EffectsPulmonaryPulmonary
– type 1:type 1: hypersensitivityhypersensitivity (after (after first few weeks) with first few weeks) with development of fever, SOB, development of fever, SOB, cough; tx : stop amio.cough; tx : stop amio.
– type 2type 2: : interstitial / alveolar interstitial / alveolar pneumonitispneumonitis (7 mos - 2 yrs); (7 mos - 2 yrs); insidious onset of non-insidious onset of non-productive cough, fatigue, productive cough, fatigue, SOB, pleuritic CP, fever; SOB, pleuritic CP, fever; infiltrates and pulmonary infiltrates and pulmonary fibrosis on CXR; tx: stop fibrosis on CXR; tx: stop amioamio
GIGI– increase in AST/ALT/ ALP (25%)increase in AST/ALT/ ALP (25%)– hepatitis, hepatic failurehepatitis, hepatic failure– N, V, A commonN, V, A common
ThyroidThyroid– inhibits conversion T4 to T3inhibits conversion T4 to T3– hypo (3%) or hyperthyroidism hypo (3%) or hyperthyroidism
(2%)(2%)– hypothyroidism:hypothyroidism:
» rare after first 18 monthsrare after first 18 months» responds to thyroid replacementresponds to thyroid replacement
– hyperthyroidismhyperthyroidism» occur at any time, difficult to occur at any time, difficult to
manage (thyroidectomy)manage (thyroidectomy)
Amiodarone: Adverse EffectsAmiodarone: Adverse Effects DermatolgicialDermatolgicial
– skin reaction (15%)skin reaction (15%)
– photosensitivity (10%)- limit sun photosensitivity (10%)- limit sun exposure and sunscreenexposure and sunscreen
– long term blue-gray discoloration long term blue-gray discoloration (1-7%)(1-7%)
CNSCNS– 40% have CNS effects (fatigue, 40% have CNS effects (fatigue,
tremor, ataxia, peripheral tremor, ataxia, peripheral neuropathy)neuropathy)
Optho. Optho. – corneal depositscorneal deposits
– rare: visual disturbancesrare: visual disturbances
– sx: photophobia, blurred vision, sx: photophobia, blurred vision, blue-green halosblue-green halos
MonitoringMonitoring– labs (renal function, CBC, labs (renal function, CBC,
LFTs, thyroid function), ECG, LFTs, thyroid function), ECG, CXR CXR
» baseline, as sx occur and baseline, as sx occur and every 4-6 monthsevery 4-6 months
– PFTs, eye exam: baseline and PFTs, eye exam: baseline and as symptoms occuras symptoms occur
– ECG, HR, BP at regular ECG, HR, BP at regular intervalsintervals
Drug InteractionsDrug Interactions– warfarin, digoxin, BB, CCB, warfarin, digoxin, BB, CCB,
procainamide, quinidineprocainamide, quinidine– (see handout)(see handout)
Drug Profile: AmiodaroneDrug Profile: Amiodarone
ADVANTAGESADVANTAGES effective in a wide range effective in a wide range
of arrhythmiasof arrhythmias neutral effects on neutral effects on
inotropy (CHF patients)inotropy (CHF patients) safety in CAD and LV safety in CAD and LV
dysfunctiondysfunction low incidence of low incidence of
proarrhythmiaproarrhythmia some rate control some rate control
properties in AFproperties in AF
LIMITATIONSLIMITATIONS many chronic side many chronic side
effects effects drug interactionsdrug interactions IV amiodarone - very IV amiodarone - very
expensiveexpensive
Drug Profile: ProcainamideDrug Profile: Procainamide Mechanism:Mechanism:
– Class 1a AA- blocks Na Class 1a AA- blocks Na channelschannels
– prolongs refractory period and prolongs refractory period and decreases conduction velocitydecreases conduction velocity
Administration/DosingAdministration/Dosing– IV and PO regimensIV and PO regimens– depends on indication and depends on indication and
renal functionrenal function– paradoxical initial increase in paradoxical initial increase in
HRHR
Kinetic ImplicationsKinetic Implications– active metabolite- NAPAactive metabolite- NAPA
– levels to prevent toxicity (drug levels to prevent toxicity (drug and NAPA)and NAPA)
Adverse EffectsAdverse Effects– hypotension, bradycardia hypotension, bradycardia – proarrhythmic (TdP)proarrhythmic (TdP)– drug-induced lupus (SLE)drug-induced lupus (SLE)– GI: nausea, vomitingGI: nausea, vomiting– CNS: disorientationCNS: disorientation
Drug InteractionsDrug Interactions– amiodarone, Septra (TMP/SMX)amiodarone, Septra (TMP/SMX)
MonitorMonitor– ECG, BP, HRECG, BP, HR