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