IV anesthesia

Thiopentone

Ketamine
Propofol

Chemical structure

Propofol
Thiopentone
Ketamine
Alkylphenol
Thiobarbiturate
Arylcyclohexylamine(phencyclidine)
OH (CH3)2CH CH(CH3)2
N O S CH3CH2 N CH3CH2CH2CH CH3
0 Cl NHCH3

Physico-chemical characteristics

FORMULATIONS

Propofol Thiopentone Ketamine

emulsion milky white
sodium salts (6% sodium carbonate by wt)
Clear aqueous solution
1%,2% & medium,long Chain Triglycerides
Yellow amorphous powder 500mg,1 g
1%,2%,10% solution

Cont…. lipid soluble

lipid soluble
lipid soluble
pH -7
10.5 of 2.5% solution
3.5 TO 5.5
pka - 11
7.6
7.5

Metabolism

Propofol liver conjugation glucuronide& sulfate excretion kidneys
Thiopentone liver

oxidation N-dealkylation desulfuration destruction of barbituric acid ring excretion kidneys bile
Ketamine liver norketamine Hydroxynorketamine excretion kidneys

Cont……… metabolites- inactive

inactive
norketamine- 20 to 30%
Extrahepatic- lungs
absent
absent

Pharmacokinetics

Propofol
Thiopentone
Ketamine
onset
one arm brain circulation
do
do
peak
90 to 100 s
90 to 100 s
90 to 100 s
awakening
5 to 10 min
5 to 10 min
10 to 20min


Rapid fall in Plasma conc after single bolus
Redistribution & Elimination
redistribution
redistribution

Cont…… Propofol

Thiopentone
Ketamine
Elimination Half life
1 to 3 hrs
7 to 17 hrs
2 to 3 hrs
clearance
(20 to 30 ml/kg/min)
(3 to 4 ml/kg/min)
(12 to 14 ml/kg/min)
Volume of distribution
2 to 10L/kg
1.5 to3L/kg
3L/kg


Propofol
Thiopentone
Ketamine
Context Sensitive Half time (for infusions lasting upto 8 hrs)
< 40 min
< 150 min
< 40 min


MOA

Propofol

Thiopentone
Ketamine
GABA
GABA
NMDA thalamocortical& limbic system


CNS


Propofol
Thiopentone
Ketamine
CMRO2
sed ( 36%)
sed (55%)
sed
CBF
sed
sed
sed
ICP
sed
sed
sed

Cont…. propofol

thiopentone
ketamine
IOP
sed ( 30 t0 40 %)
sed
sed
Neuroprotective
Reduced infarct Size when administered immediately or 1 hr after ischemic insult
Decresing oxygen demand Preserves CPP Robin hood phenomenon Free radical scavenging
Improve perfusion in incomplete cerebral ischemia

Cont….. propofol

thiopentone
Ketamine
Dissociative anaesthesia
_
--
+
Emergence reactions
--

--

+
Upper airway reflexes
--
--
+

Cont…. propofol

thiopentone
ketamine
Salivation& Lacrimation
--
--
++
Skeletal muscle tone
--
--
sed
Nystagmus
--
--
+



CVS

Propofol

Thiopentone
Ketamine
Arterial BP
sed (25 to 40 %)
sed
sed
Heart rate
Inhibits tacycardic response to hypotension
sed ( 10 to 36 %)
sed
Cardiac output
sed
sed
sed


RS


Propofol
Thiopentone
Ketamine
Apnea
++ Dose dependant ( 25 t0 30%)
++
higher doses
Minute ventilation
sed
sed
sed
Bronchodilatation

+

--
+

Doses

propofol
thiopentone
ketamine
induction
1 to 2.5 mg/kg IV
3 to 5 mg/kg IV
0.5 to 2 mg/kg IV 4 to 6mg/kg IM
maintenance
50 to 150 mic/kg/min


15 to 45 mic/kg/min IV–N2O30 TO 90 mic/kg/min sedation
25 to 75mic/kg/min
0.2 to0.8 mg/kg IV 2 to 4mg/kg IM

Cont… Analgesia

--
--
0.2 to 0.8 IV
Antiemetic
10 to 20 mg IV or 10mic/kg/min
--
--

uses

Propofol
Thiopentone
Ketamine
Induction
+
+
+
Maintenance
++
+
+
Sedation
+
--
+

Cont…… Propofol

Thiopentone
Ketamine
Analgesia
--
--
+
Pre-emptive analgesia
--
--
+
Antiemetic
+
--
--

Cont…. Antipruritic

+
--
--
Anticonvulsant
+
+
--
Chronic refractory headache
+
--
--

Side effects

Propofol
Thiopentone
Ketamine
Pain on injection
++
+
--
Hypotension
++
+
--
Apnea
++
+
+/--

Cont…. Broncho spasm

--
+
--
Allergic reactions
+
+
--
Emergence reaction
--
--
+
Thrombophle bitis
+
++
--