Ideal induction agent

Physical
Water soluble
Stable in solution
Long shelf life
No pain on injection
Not irritant subcut
Pain on arterial injection
Volume required small

Pharmacological
1 arm-brain circulation time
CVS stable
No resp depression
No histamine/hypersensitivity
Metabolized to inactive compounds
Not emetic
No excitation
Rapid clear headed recovery


Propofol

Use
Induction and maintenance anaesthesia
Sedation
Antiemetic
Status

Chemical
2,6-Diisopropylphenol

Presentation
White oil-water emulsion
1% in 20ml vials and 50ml syringes; 2% in 50ml vials/syringes
Soya bean oil, egg phosphatide and glycerol

Mechanism of action
Unclear
Acts on β subunit of GABAa receptors to
Cl conductance
Inhibits NMDA subtype of glutamate receptor

Routes of admin and doses
IV
Induction 1.5-2.5mg/kg
Infusion
Plasma conc 0.5-2mcg/ml sedation
2-8mcg/ml anaesthesia (MIC 6mcg/ml)

Effects
CVS
CO, BP, SVR (NO release)
HR
/
Attenuates response to laryngoscopy
RS
Suppression laryngeal reflexes
Respiratory depression
Bronchodilation
CNS
Smooth rapid induction in <1min
Rapid clear headed recovery
ICP, CBF, CMRO2, intraocular pressure

Antiepileptic
Dreams
Anti-emetic
Other
TG (1kcal/ml)

Toxicity and SEs
Pain on injection
Involuntary movements
Bradycardia
Green urine and hair
Propofol infusion syndrome
mortality with paediatric infusion
Is ok to use if egg allergy

Kinetics
Distribution
98% protein bound
acidic
pKa 11
99.9% unionized at pH 7.4
VD 750L

Metabolism
Congugated in liver to inactive metabolites
Extrahepatic metabolism as clearance exceeds hepatic blood flow
Liver disease has no clinically significant effect on metabolism

Excretion
Metabolites excreted in urine. <1% excreted unchanged
Clearance 2500mls/min
Context sensitive T1/2
20mins; 2h infusion
30; 6
50; 9

Other
May energy required for cardioversion
seizure duration in ECT – unimportant
Physically incompatible with atracurium
Formulation with medium chain triglycerides
pain on injection


Thiopentone

Uses
Induction
Status

Chemical
Thiobarbiturate
Acidic (stored alkaline)

Presentation
Yellow powder
Thiopentone sodium and 6% sodium carbonate (more water soluble with higher pH)
Nitrogen atmosphere (prevents oxidation)
Stable in solution for 48h

Mode of action
Acts on β subunit GABAa rec to Cl conductance

Routes of admin/doses
Induction – 3-5mg/kg
Offset by redistribution in 10mins
Can be given PR

Effects
CVS
CO by direct myocardial suppression
Little effect on SVR
RS
Respiratory depression
Airway reflexes not obtunded as much as propofol
CNS
ICP, CBF, CMRO2, intraocular pressure
Anticonvulsant
Antanalgesic
Other
Enzyme inducer

Toxicity
Very irritant if intra-arterial or extravascular injection
CI in porphyria

Kinetics
Absorption
PO and PR
Distribution
80% protein bound
Vd 200L
pKa 7.6
60% unionized at pH 7.4 (more unionized if acidotic so lower dose needed)
Metabolism
Oxidized in liver
30% may remain in body for 24h
Excretion
1% excreted unchanged
Clearance 220mls/min


Ketamine

Uses
Induction
Anaesthesia outside of hospital setting
Analgesia
Bronchospasm

Chemical
Phencyclidine derivative
Either racemic (R and S enantiomer) or S enantiomer
S enantiomer is X3-4 as potent and has shorter recovery times with less SEs

Presentation
Clear colourless liquid in 3 different concentrations (10mg/ml, 50mg/ml)
Acidic
Water soluble

Mode of action
Antagonises glutamate at NMDA receptors
Agonist at kappa and delta recs and antagonist at mu recs

Routes of admin / doses
IV, IM, PO, PR, ED, IT
1-2mg/kg for induction (5-10Mg/kg IM)
Up to 0.5mg/kg for subhypnotic doses
Onset is 1-2mins IV; 10-15mins IM

Effects
CNS
Dissociative anaesthesia
Hallucinations/delirium
ICP, CMRO2
CVS
Sympathetic stimulation
RS
Airway reflexes preserved
Respiratory stimulant
Bronchodilation
GI
N+V, salivation

Kinetics
25% protein bound
Demethylated in liver to active metabolites and further conjugation


Etomidate

DO NOT USE THIS DRUG UNDER ANY CIRCUMSTANCES

Uses
Induction

Chemical
Pure R enantiomer
Imidazole derivative
Base

Presentation
0.2% solution at pH 4.1
35% propylene glycol to improve stability and
pain on injection

Mode of action
Cl conductance at GABA recs

Routes admin/doses
IV
0.3mg/kg

Effects
CNS
Anaesthesia
Myoclonus
ICP and CBF

CVS
Minimal changes
RS
Mild respiratory depression
GI
Emetic
Toxicity/SEs
Pain on injection
Adrenocortical suppression
Inhibits steroidogenesis in adrenals by blocking of 2 enzymes 17-α-hydroxylase and 11-β-hydroxylase
Occurs after a single dose and lasts for 8h
Subgroup analysis in CORTICUS trial showed increased mortality in etomidate group.

Kinetics
75% protein bound
Vd 250
pKa 4.2 99.9 % unionized at 7.4
Hepatic metabolism