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
