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Pharmacology of Antiarrhythmics Pharmacology of Antiarrhythmics and Vasoactive Substancesand Vasoactive Substances
Department of pharmacologyDepartment of pharmacology
Liming zhouLiming zhou
2010,spring2010,spring
Cardiac AnatomyCardiac Anatomy
Cardiac Action PotentialCardiac Action Potential
0 – Depolarisation due to opening of 0 – Depolarisation due to opening of NaNa++ channels. channels.
1 – Repolarisation due to inactivation 1 – Repolarisation due to inactivation of Naof Na++ channels (fast Na channels (fast Na++ channels, channels, activation of Kactivation of K++ channels that let K channels that let K++ out of the cell.out of the cell.
2 – Plateau phase. Due to slow inward 2 – Plateau phase. Due to slow inward current caused by Cacurrent caused by Ca2+2+ channels (L- channels (L-type Catype Ca2+2+ channels) opening. This Ca channels) opening. This Ca2+2+ influx also leads to cardiac muscle influx also leads to cardiac muscle contraction.contraction.
3 – Repolarisation due to K3 – Repolarisation due to K++ leaving leaving cells.cells.
4 – Spontaneous depolarisation to 4 – Spontaneous depolarisation to threshold where critical voltage threshold where critical voltage activates Naactivates Na++ channels. If this phase channels. If this phase is steeper, then heart rate increases. is steeper, then heart rate increases. Involves the spontaneous action of Involves the spontaneous action of various channel types.various channel types.
How is cardiac contraction How is cardiac contraction triggered?triggered?
CaCa2+2+-induced Ca-induced Ca2+2+ release mechanism release mechanism (+ve feedback) caused by Ca(+ve feedback) caused by Ca2+2+ binding binding to receptors on sarcoplasmic reticulum to receptors on sarcoplasmic reticulum (SR)(SR)
Actin and myosin filaments activated Actin and myosin filaments activated when [Cawhen [Ca2+2+]]ii rises rises
This is the SLIDING FILAMENT This is the SLIDING FILAMENT THEORYTHEORY
The ryanodine receptor exists on the SR The ryanodine receptor exists on the SR in many cell types and triggers Cain many cell types and triggers Ca2+2+ releaserelease
Ryanodine is a plant alkaloid that can Ryanodine is a plant alkaloid that can bind to receptorsbind to receptors
Ryanodine receptors are composed of 4 Ryanodine receptors are composed of 4 identical sub-units, exists in T-tubules, identical sub-units, exists in T-tubules, and allows release of Caand allows release of Ca2+2+ from the SR from the SR into the cytosolinto the cytosol
Cardiac muscle and tetanusCardiac muscle and tetanus
Skeletal muscle – only active Skeletal muscle – only active when contraction requiredwhen contraction required
Cardiac muscle – only relaxes in Cardiac muscle – only relaxes in between beats for short periods between beats for short periods and must remain activeand must remain active
Cardiac ATP supply must be maintained:Cardiac ATP supply must be maintained:
•Mitochondria are larger and greater in Mitochondria are larger and greater in numbernumber
•Cells contain myoglobin for more Cells contain myoglobin for more efficient use and storage of Oefficient use and storage of O22
Skeletal muscle can produce a Skeletal muscle can produce a maintained contraction (tetanus)maintained contraction (tetanus)
Cardiac muscle unable to produce Cardiac muscle unable to produce tetanus since prolonged refractory period tetanus since prolonged refractory period prevents re-excitationprevents re-excitation
Frank-Starling MechanismFrank-Starling Mechanism
As blood moves into the heart, it As blood moves into the heart, it stretches the cardiac musclestretches the cardiac muscle
In exercise, more blood enters the In exercise, more blood enters the heart, stretching it even moreheart, stretching it even more
Extra stretch produces extra forceExtra stretch produces extra force
Expels larger volume of bloodExpels larger volume of blood
Enables us to handle increased blood Enables us to handle increased blood volumevolume
Unique to cardiac muscleUnique to cardiac muscle
Thus, we have increased force on Thus, we have increased force on demanddemand
Frank-Starling MechanismFrank-Starling Mechanism
Most important function is to balance Most important function is to balance the outputs of left and right ventriclesthe outputs of left and right ventricles
If output of right ventricle exceeds left:If output of right ventricle exceeds left:• Pulmonary volume increasesPulmonary volume increases• Increased pressure in pulmonary veinsIncreased pressure in pulmonary veins• Left ventricular (LV) filling pressure increasesLeft ventricular (LV) filling pressure increases• LV becomes more distended (stretched)LV becomes more distended (stretched)• Increased stroke volumeIncreased stroke volume
Why can the myocardium increase Why can the myocardium increase force of contraction in response to force of contraction in response to increased filling pressure?increased filling pressure?
2 mechanisms:2 mechanisms: (1) Overlap of actin filaments causing mechanical (1) Overlap of actin filaments causing mechanical
interference at sarcomere lengths below 2 mM, so interference at sarcomere lengths below 2 mM, so need to stretch more to contract muscle moreneed to stretch more to contract muscle more
sarcomere
(2) As muscles stretched, sensitivity (2) As muscles stretched, sensitivity to calcium increases (this may to calcium increases (this may involve troponin, the protein that involve troponin, the protein that regulates access to binding sites on regulates access to binding sites on actin)actin)
Mechanism of arrhythmicMechanism of arrhythmic
Antiarrhythmic drugAntiarrhythmic drug
Antiarrhythmic ClassificationAntiarrhythmic Classification
Class I - Fast Channel BlockersClass I - Fast Channel Blockers
• Ia - Quinidine, Disopyramide, ProcainaIa - Quinidine, Disopyramide, Procainamidemide
• Ib - Lidocaine, Phenytoin, Mexilitine, TIb - Lidocaine, Phenytoin, Mexilitine, Tocainindeocaininde
• Ic - Ecainide, Flecainide, Propafenone, Ic - Ecainide, Flecainide, Propafenone, Indecainide, MoricizineIndecainide, Moricizine
Antiarrhythmic ClassificationAntiarrhythmic Classification
Class II - Beta BlockersClass II - Beta Blockers
• Propanolol, Acebutolol, Atenolol, BetaxPropanolol, Acebutolol, Atenolol, Betaxolol, Bisoprolol, Esmolol, Labetalol, Metolol, Bisoprolol, Esmolol, Labetalol, Metoprolol, Nadolol, Oxprenolol, Penbutolooprolol, Nadolol, Oxprenolol, Penbutolol, Pindolol, Sotalol, Timololl, Pindolol, Sotalol, Timolol
Antiarrhythmic ClassificationAntiarrhythmic Classification
Class IIIClass III
• Bretylium, Amiodarone, SotalolBretylium, Amiodarone, Sotalol
Class IV - Calcium Channel BlockersClass IV - Calcium Channel Blockers
• Verapamil, DiltiazemVerapamil, Diltiazem
Unclassified - Digoxin, Adenosine, MgUnclassified - Digoxin, Adenosine, Mg
Procainamide - ActionsProcainamide - Actions
Suppresses automaticity Suppresses automaticity • decreasing the rate and amplitude of phdecreasing the rate and amplitude of ph
ase 4 diastolic depolarizationase 4 diastolic depolarization• prolongs action potential durationprolongs action potential duration• reduces the speed of impulse conductionreduces the speed of impulse conduction• suppresses fibrillatory activity in the atrisuppresses fibrillatory activity in the atri
a and ventriclesa and ventricles Dose dependant anticholinergic activityDose dependant anticholinergic activity
Procainamide - ActionsProcainamide - Actions
Negative InotropeNegative Inotrope
• more pronounced in ischemic myocardimore pronounced in ischemic myocardiumum
Hypotension in high dosesHypotension in high doses
• vasodilatation of peripheral vasculaturevasodilatation of peripheral vasculature
Procainamide- PharmacokineticsProcainamide- Pharmacokinetics
OnsetOnset• 5 - 10 minutes IV5 - 10 minutes IV• 15 - 60 minutes IM15 - 60 minutes IM
Half LifeHalf Life• 2.5 to 4.7 hrs in normal renal function2.5 to 4.7 hrs in normal renal function• increased in CHF, Renal Failureincreased in CHF, Renal Failure
Metabolized to N-acetyl ProcainamideMetabolized to N-acetyl Procainamide• NAPANAPA
Procainamide - IndicationsProcainamide - Indications
Ventricular arrhythmiasVentricular arrhythmias
• Stable Ventricular TachycardiaStable Ventricular Tachycardia
• Premature Ventricular ContractionsPremature Ventricular Contractions
• Ventricular Fibrillation / Pulseless VTVentricular Fibrillation / Pulseless VT Supraventricular tachyarrhythmiasSupraventricular tachyarrhythmias
• PSVT, PAT, paroxysmal AV junctionalPSVT, PAT, paroxysmal AV junctional
• Atrial flutter and fibrillationAtrial flutter and fibrillation
Procainamide- ContraindicationsProcainamide- Contraindications
AV block AV block
• Second or third degreeSecond or third degree Long QT intervalLong QT interval Torsade de pointesTorsade de pointes Caution Caution
• SLE, CHF, hepatic or renal diseaseSLE, CHF, hepatic or renal disease
Procainamide - AdministrationProcainamide - Administration
Continuous infusion safer than bolusContinuous infusion safer than bolus Infusion of 20 - 30 mg/min untilInfusion of 20 - 30 mg/min until
• control of arrhythmiacontrol of arrhythmia
• hypotensionhypotension
• QRS widens by > 50%QRS widens by > 50%
• QT interval prolongationQT interval prolongation
• Total of 17 mg/kg has been administeredTotal of 17 mg/kg has been administered
Procainamide - AdministrationProcainamide - Administration
Once ectopy is suppressedOnce ectopy is suppressed
• maintenance drip of 1 to 4 mg/minmaintenance drip of 1 to 4 mg/min Lower doses for CHF and renal failureLower doses for CHF and renal failure
Procainamide - Adverse EffectsProcainamide - Adverse Effects
Myocardial DepressionMyocardial Depression• prolonged QRS, QT, AV conduction, VF and prolonged QRS, QT, AV conduction, VF and
Torsade de pointesTorsade de pointes HypotensionHypotension• High doses or rapidly administeredHigh doses or rapidly administered
HypersensitivityHypersensitivity• angioedema, bronchoconstriction, vascular coangioedema, bronchoconstriction, vascular co
llapse, febrile episodes, respiratory arrestllapse, febrile episodes, respiratory arrest
Lidocaine - ActionsLidocaine - Actions
Class IB antiarrhythmicClass IB antiarrhythmic• blocks fast sodium channelsblocks fast sodium channels• decreases slope of phase 4decreases slope of phase 4• decreased automaticity in the His-purkinje sysdecreased automaticity in the His-purkinje sys
temtem• action potential duration and effective refractoaction potential duration and effective refracto
ry period of His-purkinje increasedry period of His-purkinje increased• Acts preferentially on ischemic tissueActs preferentially on ischemic tissue
Lidocaine - ActionsLidocaine - Actions
ContinuedContinued• Causes little or no effect on AV conductionCauses little or no effect on AV conduction• Elevates v-fib thresholdElevates v-fib threshold• Supresses ventricular ectopySupresses ventricular ectopy• negligible effect negligible effect – autonomic nervous system autonomic nervous system –myocardial contractility myocardial contractility – peripheral vascular toneperipheral vascular tone
Lidocaine -PharmacokineticsLidocaine -Pharmacokinetics
Onset of ActionOnset of Action• 30 to 60 seconds IV30 to 60 seconds IV• 10 minutes IM10 minutes IM
Bolus administration necessaryBolus administration necessary• infusion alone will not reach therapeutic infusion alone will not reach therapeutic
levels for 30 min to several hrs.levels for 30 min to several hrs. First pass metabolismFirst pass metabolism• No PO formNo PO form
Lidocaine - PharmacokineticsLidocaine - Pharmacokinetics
Half-Life (elimination)Half-Life (elimination)• 80 to 108 minutes 80 to 108 minutes – healthy patientshealthy patients
• 7 hrs 7 hrs – in patients with CHF, liver diseasein patients with CHF, liver disease
Therapeutic LevelsTherapeutic Levels• 1.5 to 6 ug/ml1.5 to 6 ug/ml• >5 ug/ml may cause CNS toxicity>5 ug/ml may cause CNS toxicity
Lidocaine - IndicationsLidocaine - Indications Drug of Choice Drug of Choice • ventricular arrhythmiasventricular arrhythmias• ventricular ectopyventricular ectopy
frequent multifocal PVC’s (>6/min)frequent multifocal PVC’s (>6/min)–PVC couplets, salvosPVC couplets, salvos– long runs of VTlong runs of VT–Not used for chronic PVC’s when asymptomaticNot used for chronic PVC’s when asymptomatic
Prophylactic use Prophylactic use • No longer recommendedNo longer recommended
Lidocaine - AdministrationLidocaine - Administration
Initial Dose IVInitial Dose IV• Ventricular EctopyVentricular Ectopy– 1 mg/kg bolus1 mg/kg bolus– additional doses of 0.5 mg/kg q 5-10 minadditional doses of 0.5 mg/kg q 5-10 min
• Ventricular FibrillationVentricular Fibrillation– 1.5 mg/kg1.5 mg/kg
Total Dose IVTotal Dose IV• 3 mg/kg3 mg/kg
Lidocaine - AdministrationLidocaine - Administration
EndotrachealEndotracheal• If IV not availableIf IV not available• 2 to 2 2 to 2 1/21/2 times the dose diluted to total vo times the dose diluted to total vo
lume of 10 cc’slume of 10 cc’s IMIM• 300 mg of 10% solution, deltoid vastus l300 mg of 10% solution, deltoid vastus l
ateralis ateralis • Auto- injectors availableAuto- injectors available
Lidocaine - Adverse EffectsLidocaine - Adverse Effects
CNS side effectsCNS side effects Abrupt change in mental statusAbrupt change in mental status Plasma levels greater than 9 ug/mlPlasma levels greater than 9 ug/ml• psychosis, seizures, respiratory depressionpsychosis, seizures, respiratory depression
ContraindicatedContraindicated• SA or AV blocksSA or AV blocks• Known hypersensitivityKnown hypersensitivity
Beta Blockers - ActionsBeta Blockers - Actions
Block effects of catacholamines on Beta receptorBlock effects of catacholamines on Beta receptorss
Selective Beta blockersSelective Beta blockers• metoprolol metoprolol • acebutololacebutolol• atenololatenolol• esmololesmolol• metoprololmetoprolol
Beta Blockers - ActionsBeta Blockers - Actions
NegativeNegative
• ChronotropicChronotropic
–slows sinus rateslows sinus rate
–depresses AV conductiondepresses AV conduction
–Decreases cardiac outputDecreases cardiac output
• InotropicInotropic VasodilatationVasodilatation
Phillip L. Coule, M.D. Medical College of Georgia Emergency MedicinePhillip L. Coule, M.D. Medical College of Georgia Emergency Medicine
Beta Blockers- PharmacokineticsBeta Blockers- Pharmacokinetics
OnsetOnset
• rapid - within 1 minute IVrapid - within 1 minute IV Half Life Half Life
• 1 to 26 hours1 to 26 hours
• Excretion is renal and GIExcretion is renal and GI Dose adjustment necessary for renal Dose adjustment necessary for renal
failure for some beta blockers failure for some beta blockers
Beta Blockers - AdministrationBeta Blockers - Administration
MetoprololMetoprolol• 5 mg IV push5 mg IV push• selective B1selective B1• Half life of 3-7 hrsHalf life of 3-7 hrs
EsmololEsmolol• ultra-short half life of 9 minutesultra-short half life of 9 minutes• 25-50 ug/kg/min25-50 ug/kg/min• load of 500 ug/kg not necessaryload of 500 ug/kg not necessary
Beta Blockers - Adverse EffectsBeta Blockers - Adverse Effects
Similar for most Beta blockersSimilar for most Beta blockers• nausea, vomiting, light headedness, mennausea, vomiting, light headedness, men
tal depression, bradycardia, hypotensiontal depression, bradycardia, hypotension, bronchospasm, bronchospasm
ContraindicatedContraindicated• > first degree heart block> first degree heart block• CHF or cardiogenic shockCHF or cardiogenic shock• Caution with calcium channel blockersCaution with calcium channel blockers
Bretylium - ActionsBretylium - Actions
Class IIIClass III Biphasic EffectsBiphasic Effects• Norepinephrine releaseNorepinephrine release–effects last 20 minuteseffects last 20 minutes
• Blocks release of norepinephrineBlocks release of norepinephrine–45 to 60 minutes after administration45 to 60 minutes after administration
• Affects phase 3 (repolarization) prolongAffects phase 3 (repolarization) prolongs refractoriness - antifibrillatorys refractoriness - antifibrillatory
Bretylium - IndicationsBretylium - Indications
VFVF• refractory VF, after epinephrine, lidocairefractory VF, after epinephrine, lidocai
nene VTVT• refractory VT with a pulse, after lidocairefractory VT with a pulse, after lidocai
ne and procainamidene and procainamide Wide Complex Tachycardia UnknownWide Complex Tachycardia Unknown• after lidocaine and adenosineafter lidocaine and adenosine
Bretylium - AdministrationBretylium - Administration
VF or Pulseless VTVF or Pulseless VT
• 5 mg/kg rapid IV push5 mg/kg rapid IV push
• repeat at 10 mg/kg in 15 to 30 minutesrepeat at 10 mg/kg in 15 to 30 minutes
• maximum is 35 mg/kgmaximum is 35 mg/kg VT / ventricular arrhythmiasVT / ventricular arrhythmias
• 5 - 10 mg.kg over 8 to 10 minutes5 - 10 mg.kg over 8 to 10 minutes Maintenance of 1-2 mg/minMaintenance of 1-2 mg/min
Diltiazem - ActionsDiltiazem - Actions
Class IV - Calcium Channel BlockerClass IV - Calcium Channel Blocker
• decreases conduction velocity in decreases conduction velocity in diseased tissuediseased tissue
• prolongs refractory period in AV nodeprolongs refractory period in AV node
• slows discharge from SA nodeslows discharge from SA node
• minimal effect on normal tissue minimal effect on normal tissue
• Interrupts reentrant pathway in PSVTInterrupts reentrant pathway in PSVT
Diltiazem - IndicationsDiltiazem - Indications
Rapid Conversion of PSVTRapid Conversion of PSVT
• as effective as adenosine and verapamilas effective as adenosine and verapamil Slowing of rate in A-Fib or A-flutterSlowing of rate in A-Fib or A-flutter HypertensionHypertension
Diltiazem - AdministrationDiltiazem - Administration
PSVT, A-fib, A-flutterPSVT, A-fib, A-flutter
• .25 mg/kg (average 20 mg) over 2 .25 mg/kg (average 20 mg) over 2 minutesminutes
• Second bolus of .35 mg/kgSecond bolus of .35 mg/kg Maintenance InfusionMaintenance Infusion
• 5-15 mg/hr5-15 mg/hr
Diltiazem - Adverse EffectsDiltiazem - Adverse Effects
CardiovascularCardiovascular
• angina, bradycardia, asystole, CHF, AV angina, bradycardia, asystole, CHF, AV block, BBB, flushing, hypotensionblock, BBB, flushing, hypotension
Non-cardiovascularNon-cardiovascular
• headache, dizziness, constipation, rashheadache, dizziness, constipation, rash
Adenosine - ActionsAdenosine - Actions
Endogenous NucleosideEndogenous Nucleoside• produced by dephosphorylation of ATPproduced by dephosphorylation of ATP
Negative Chronotropic effects on SA and AV Negative Chronotropic effects on SA and AV nodenode• Does not alter accessory pathwaysDoes not alter accessory pathways• blockade of the AV nodeblockade of the AV node• potent vasodilator - no effects due to metabpotent vasodilator - no effects due to metab
olismolism
Adenosine - PharmacokineticsAdenosine - Pharmacokinetics
OnsetOnset
• 30 seconds30 seconds Duration Duration
• 60 to 90 seconds60 to 90 seconds Half-life Half-life
• less than 7 secondsless than 7 seconds
Adenosine - IndicationsAdenosine - Indications
Emergency management of PSVTEmergency management of PSVT
• involving the AV nodeinvolving the AV node DiagnosticDiagnostic
• Wide complex tachycardia of uncertain Wide complex tachycardia of uncertain originorigin
• detection of accessory pathwaysdetection of accessory pathways
Adenosine - AdministrationAdenosine - Administration
6 mg Rapid IV push (over 1-2 seconds)6 mg Rapid IV push (over 1-2 seconds)
• most proximal portmost proximal port
• followed by 20 ml saline flushfollowed by 20 ml saline flush
• elevate the extremity after boluselevate the extremity after bolus Repeat DosingRepeat Dosing
• 12 mg rapid IV push if heart rate not 12 mg rapid IV push if heart rate not decreased in 2 minutesdecreased in 2 minutes
Adenosine - Adverse EffectsAdenosine - Adverse Effects
Minor and well toleratedMinor and well tolerated• less than 1 minuteless than 1 minute• dyspnea, cough, syncope, vertigo, parastdyspnea, cough, syncope, vertigo, parast
hesiashesias Higher dosesHigher doses• DipyramidoleDipyramidole• CarbamazepineCarbamazepine• Asthmatics, excessive coffee drinkersAsthmatics, excessive coffee drinkers
Magnesium - ActionsMagnesium - Actions
DirectlyDirectly• Na, K+, ATPase pumpNa, K+, ATPase pump
IndirectlyIndirectly• calcium channel blocking activitycalcium channel blocking activity
EffectsEffects• Increases membrane potentialIncreases membrane potential• prolongs AV conductionprolongs AV conduction• Corrects hypomagnesemia/hypokalemiaCorrects hypomagnesemia/hypokalemia
Magnesium - IndicationsMagnesium - Indications
Intractable VF/VTIntractable VF/VT Torsade de pointesTorsade de pointes May be usefulMay be useful
• PVC’s, MAT, PSVT, digoxin toxicityPVC’s, MAT, PSVT, digoxin toxicity
Magnesium - AdministrationMagnesium - Administration
IV Loading doseIV Loading dose
• 1 to 2 grams in 50-100 cc of D5W over 1 1 to 2 grams in 50-100 cc of D5W over 1 to 2 minutesto 2 minutes
Acute MIAcute MI
• 8 to 12 grams per day in acute MI8 to 12 grams per day in acute MI
Vasoactive MedicationsVasoactive Medications
EpinephrineEpinephrine DopamineDopamine NorepinephrineNorepinephrine AtropineAtropine NitroglycerinNitroglycerin
Epinephrine - OverviewEpinephrine - Overview
Nonselective alpha and beta agonistNonselective alpha and beta agonist
• increased heart rate, SVR, ventricular increased heart rate, SVR, ventricular contractilitycontractility
Onset Onset
• 1 to 2 minutes1 to 2 minutes Duration of action Duration of action
• 2 to 10 minutes2 to 10 minutes
Epinephrine - ContinuedEpinephrine - Continued
IndicationsIndications• Cardiac ArrestCardiac Arrest• Bronchospasm Bronchospasm • Anaphylaxis / hypersensitivity reactionsAnaphylaxis / hypersensitivity reactions
AdministrationAdministration• Cardiac ArrestCardiac Arrest– 1 mg IV push every 3 - 5 minutes1 mg IV push every 3 - 5 minutes– escalating and high dose optionsescalating and high dose options
Epinephrine - ContinuedEpinephrine - Continued
• EndotrachealEndotracheal– 2 to 2.5 the IV dose diluted to 10 cc2 to 2.5 the IV dose diluted to 10 cc
Adverse EffectsAdverse Effects
• may increase myocardial oxygen consumay increase myocardial oxygen consumptionmption
Dopamine - OverviewDopamine - Overview
ActionsActions• acts on dopaminergic, alpha and beta receptoracts on dopaminergic, alpha and beta receptor
ss Low DoseLow Dose• dilatation of renal, mesenteric, coronary, and idilatation of renal, mesenteric, coronary, and i
ntracerebral vascular bedsntracerebral vascular beds• improves organ perfusion and increases urine improves organ perfusion and increases urine
outputoutput
Dopamine - ContinuedDopamine - Continued
Moderate Dose 2 - 10 ug/kg/minModerate Dose 2 - 10 ug/kg/min• mostly beta effects mostly beta effects – inotropic, chronotropic on heartinotropic, chronotropic on heart– increased cardiac outputincreased cardiac output
High Dose >10 ug/kg/minHigh Dose >10 ug/kg/min• Alpha effects predominateAlpha effects predominate– increased peripheral resistanceincreased peripheral resistance– decreased blood flow to kidneydecreased blood flow to kidney
Norepinephrine - OverviewNorepinephrine - Overview
Endogenous CatacholamineEndogenous Catacholamine• powerful alpha agonistpowerful alpha agonist• potent vasoconstrictorpotent vasoconstrictor
Onset Onset • 1 to 3 minutes1 to 3 minutes
IndicationsIndications• severe hypotension refractory to fluids and othsevere hypotension refractory to fluids and oth
er pressor agentser pressor agents
Norepinephrine - ContinuedNorepinephrine - Continued
Specific UsesSpecific Uses
• Septic ShockSeptic Shock
• refractory hypotension due to AMIrefractory hypotension due to AMI DosingDosing
• 0.5 to 1 ug/kg/min0.5 to 1 ug/kg/min– increase by 1 to 2 ug/kg/min every 3-5 min increase by 1 to 2 ug/kg/min every 3-5 min – goal is systolic BP of 80 to 100 goal is systolic BP of 80 to 100
Norepinephrine - ContinuedNorepinephrine - Continued
Adverse EffectsAdverse Effects• ventricular irritabilityventricular irritability• cardiac depressioncardiac depression• decreased renal blood flowdecreased renal blood flow• reflex bradycardiareflex bradycardia• acute hypertensionacute hypertension–MAOI, TCA’sMAOI, TCA’s
• Extravasation necrosisExtravasation necrosis– pentolamine 5-10 mg/10 cc subcutaneouspentolamine 5-10 mg/10 cc subcutaneous
Atropine OverviewAtropine Overview
Antimuscarinic AgentAntimuscarinic Agent• parasympatholytic / vagolyticparasympatholytic / vagolytic– increases SA node automaticity by bloincreases SA node automaticity by blo
cking vagus nervecking vagus nerve IndicationsIndications• hemodynamically unstable bradycardiashemodynamically unstable bradycardias• PEA, Asystole, bradyasystolic rhythmsPEA, Asystole, bradyasystolic rhythms• anticholinergic propertiesanticholinergic properties
Atropine ContinuedAtropine Continued
DoseDose• 0.5 to 1 mg IV0.5 to 1 mg IV
EndotrachealEndotracheal• 1 to 2 mg IV (10 cc volume)1 to 2 mg IV (10 cc volume)
Adverse effectsAdverse effects• increased MVO2increased MVO2• undesirable tachycardiaundesirable tachycardia• precipitate ventricular arrhythmiasprecipitate ventricular arrhythmias
SummarySummary
Pharmacology of antiarrhythmic and vasoPharmacology of antiarrhythmic and vasoactive medicationsactive medications
• ActionsActions
• PharmacokineticsPharmacokinetics
• IndicationsIndications
• AdministrationAdministration
• Adverse EffectsAdverse Effects
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