Moderator:Dr vijeshModerator:Dr vijesh Presenter:Dr Nikhil M PPresenter:Dr Nikhil M P

Thiopentone

Ketamine

Propofol

Chemical Chemical structurestructure

PropofolPropofol ThiopentoneThiopentone

Ketamine Ketamine

AlkylphenolAlkylphenol

ThiobarbiturateThiobarbiturate ArylcyclohexArylcyclohexylamine(pheylamine(phencyclidine)ncyclidine)

OHOH

(CH3)2CH CH(CH3)2(CH3)2CH CH(CH3)2

N N

O SO S

CH3CH2 CH3CH2 N N

CH3CH2CH2CHCH3CH2CH2CH

CH3 CH3

00

ClCl

NHCH3NHCH3

Physico-chemical Physico-chemical characteristicscharacteristics

FORMULATIONSFORMULATIONS

Propofol Propofol ThiopentoneThiopentone KetamineKetamine

emulsion emulsion

milky whitemilky white sodium saltssodium salts

(6% sodium (6% sodium carbonate by carbonate by wt)wt)

Clear aqueous Clear aqueous solution solution

1%,2% & 1%,2% & medium,longmedium,long

Chain Chain TriglyceridesTriglycerides

Yellow Yellow amorphous amorphous powderpowder

500mg,1 g500mg,1 g

1%,2%,10% 1%,2%,10% solutionsolution

Cont….Cont….

lipid lipid solublesoluble

lipid lipid solublesoluble

lipid lipid solublesoluble

pH -7pH -7 10.5 of 2.5% 10.5 of 2.5%

solutionsolution

3.5 TO 5.53.5 TO 5.5

pka - 11pka - 11 7.67.6 7.57.5

Metabolism Metabolism

PropofolPropofol

liverliver

conjugationconjugation

glucuronide&glucuronide&

sulfatesulfate

excretionexcretion

kidneyskidneys

Thiopentone Thiopentone

liverliver

oxidationoxidation

N-N-dealkylationdealkylation

desulfurationdesulfuration

destruction of destruction of barbituric barbituric acid ringacid ring

excretionexcretion

kidneyskidneys

bilebile

KetamineKetamine

liverliver

norketaminenorketamine

HydroxynorketHydroxynorketamineamine

excretionexcretion

kidneyskidneys

Cont………Cont………

metabolites-metabolites-

inactiveinactive inactiveinactive

norketamine-norketamine-

20 to 30%20 to 30%

Extrahepatic-Extrahepatic-

lungs lungs absentabsent absentabsent

PharmacokineticsPharmacokinetics

PropofolPropofol ThiopentoThiopentonene

KetamineKetamine

onsetonset one armone arm

brain brain circulation circulation

dodo dodo

peakpeak 90 to 100 s90 to 100 s 90 to 100 s90 to 100 s 90 to 100 s90 to 100 s

awakeningawakening 5 to 10 5 to 10

minmin5 to 10 5 to 10 minmin

10 to 10 to 20min20min

Rapid fall Rapid fall in in

Plasma Plasma conc after conc after single single bolus bolus

RedistributioRedistributionn

&&

EliminationElimination

redistributiredistributionon

redistributiredistributionon

Cont……Cont……

PropofolPropofol ThiopentoThiopentonene

KetamineKetamine

EliminatioEliminationn

Half lifeHalf life 1 to 3 hrs1 to 3 hrs 7 to 17 hrs7 to 17 hrs 2 to 3 hrs2 to 3 hrs

clearanceclearance

(20 to 30 (20 to 30 ml/kg/min)ml/kg/min)

(3 to 4 (3 to 4 ml/kg/min)ml/kg/min)

(12 to 14 (12 to 14 ml/kg/min)ml/kg/min)

Volume of Volume of distributiodistributionn

2 to 2 to 10L/kg10L/kg

1.5 1.5 to3L/kgto3L/kg

3L/kg3L/kg

PropofolPropofol ThiopentoThiopentonene

KetamineKetamine

ContextContext

SensitiveSensitive

Half timeHalf time(for (for infusions infusions lasting upto lasting upto 8 hrs)8 hrs)

< 40 min< 40 min < 150 < 150 minmin

< 40 < 40 minmin

MOAMOA

PropofolPropofol Thiopentone Thiopentone KetamineKetamine

GABAGABA

GABAGABA

NMDANMDA

thalamocorticthalamocortical& limbic al& limbic systemsystem

CNSCNS

PropofolPropofol ThiopentoThiopentonene

KetaminKetaminee

CMRO2CMRO2 sedsed

( 36%)( 36%)

sedsed

(55%)(55%)

sedsed

CBFCBF sedsed sedsed sedsed

ICPICP sedsed sedsed sedsed

Cont….Cont…. propofolpropofol thiopentothiopento

nene ketamineketamine

IOPIOP sedsed( 30 t0 40 %)( 30 t0 40 %)

sedsed sedsed

NeuroprotNeuroprotectiveective

Reduced Reduced infarctinfarct

Size when Size when administered administered immediately immediately or 1 hr after or 1 hr after ischemic ischemic insultinsult

Decresing Decresing oxygen oxygen demanddemandPreserves Preserves CPPCPPRobin hood Robin hood phenomenonphenomenonFree radical Free radical scavengingscavenging

Improve Improve perfusion in perfusion in incomplete incomplete cerebral cerebral ischemiaischemia

ContCont…..….. propofolpropofol thiopentothiopento

neneKetamine Ketamine

DissociativDissociativee

anaesthesianaesthesiaa

_ _ ---- ++

Emergence Emergence reactionsreactions

-- --

----

++

Upper Upper airway airway reflexesreflexes -- -- -- -- ++

Cont….Cont…. propofolpropofol thiopentonthiopenton

ee ketamineketamine

SalivationSalivation&&

LacrimatioLacrimationn

-- --

---- ++++

Skeletal Skeletal muscle muscle tonetone ---- ---- sedsed

NystagmuNystagmuss

-- -- ---- ++

CVSCVS

PropofolPropofol ThiopentoThiopentonene

KetamineKetamine

Arterial Arterial BPBP

sedsed (25 to 40 %)(25 to 40 %)

sedsed sedsed

Heart Heart raterate

Inhibits Inhibits tacycardic tacycardic response to response to hypotensiohypotensionn

sedsed( 10 to 36 %)( 10 to 36 %)

sedsed

Cardiac Cardiac outputoutput

sedsed sedsed sedsed

RSRS

PropofolPropofol ThiopentoThiopentonene

KetamineKetamine

ApneaApnea ++++Dose Dose dependantdependant

( 25 t0 30%)( 25 t0 30%)

++++ higher higher dosesdoses

Minute Minute ventilatioventilationn

sedsed sedsed

sedsed

BronchodilBronchodilatation atation

++ ---- ++

DosesDoses

propofolpropofol thiopentothiopentonene

ketamineketamine

inductioninduction 1 to 2.5 1 to 2.5 mg/kg IVmg/kg IV

3 to 5 3 to 5 mg/kg IVmg/kg IV

0.5 to 2 0.5 to 2 mg/kg IVmg/kg IV

4 to 6mg/kg 4 to 6mg/kg IMIM

maintenanmaintenancece

50 to 150 50 to 150 mic/kg/minmic/kg/min

15 to 45 15 to 45 mic/kg/min mic/kg/min IV–N2OIV–N2O

30 TO 90 30 TO 90 mic/kg/min mic/kg/min

sedation sedation 25 to 25 to 75mic/kg/m75mic/kg/minin

0.2 to0.8 0.2 to0.8 mg/kg IVmg/kg IV

2 to 4mg/kg 2 to 4mg/kg IMIM

Cont…Cont…

AnalgesiAnalgesiaa

---- ---- 0.2 to 0.80.2 to 0.8

IV IV

AntiemetiAntiemeticc

10 to 20 10 to 20 mg IV or mg IV or

10mic/kg/10mic/kg/minmin

---- ----

usesuses

PropofolPropofol ThiopentoThiopentonene

KetamineKetamine

InductionInduction ++ ++ ++

MaintenanMaintenancece

++++ ++ ++

SedationSedation ++ ---- ++

Cont……Cont……PropofolPropofol ThiopentoThiopento

neneKetamineKetamine

AnalgesiaAnalgesia ---- -- --

++

Pre-Pre-emptive emptive analgesiaanalgesia ---- ---- ++

AntiemeticAntiemetic ++ ---- ----

Cont….Cont….AntipruritAntipruriticic

++ ---- ----

AnticonvuAnticonvulsantlsant

++ ++ ----

Chronic Chronic refractory refractory headacheheadache ++ ---- ----

Side effectsSide effects

PropofolPropofol ThiopentoThiopentonene

KetamineKetamine

Pain on Pain on injectioninjection ++++ ++ ----

HypotensiHypotensionon ++++ ++ ----

ApneaApnea

++++ ++ +/--+/--

Cont….Cont…. BronchoBroncho

spasmspasm

---- ++ ----

Allergic Allergic reactionsreactions

++ ++ ----

Emergence Emergence reactionreaction

---- ---- ++

ThrombopThrombophlehle

bitisbitis ++ ++++ ----

ReferancesReferances

Millers anesthesia,6Millers anesthesia,6thth edition edition

Clinical anaesthesia,Barash,5Clinical anaesthesia,Barash,5thth editionedition

Stoeltings pharmacology,4Stoeltings pharmacology,4thth edition edition

Clinical anaesthesiology,Morgan,4Clinical anaesthesiology,Morgan,4thth

editionedition