INDUCTION AGENTS- Peck and Hill Flashcards
THIOPENTAL:
? molecular form
? storage/ formulation
Form: sulphur analogue of oxybarbituate pentobarbital.
Stored:
- formulated as a sodium salt, presented as pale yellow powder.
- 6% sodium carbonate, and nitrogen instead of air.
- Forms alkaline solution - pH 10.5 - more water soluble.
- 2.5% solution.
THIOPENTAL:
? Induction dose
? Uses
3-7 mg/kg
Used for GA induction,
also as infusion to control status epilepticus - produces isoelectric EEG.
THIOPENTAL:
? effect on HR, Contractility, SVR, MAP, RESP, CBF
Increases heart rate and decreases all else.
THIOPENTAL: ? kinetics - pKa - % unionised at physiological pH - % protein bound - lipid/water soluble?
pKa 7.6 therefore 60% unionized at pH 7.4
Highly protein bound - 80%
(Greater fraction free available drug when less protein available for binding.)
Therefore only 12% is available immediately in the unbound unionised form, still rapid onset due to high lipid solubility.
THIOPENTAL:
? problems with intra-arterial injection
As 2.5% thiopental at pH 10.5 is injected into blood with pH 7.4, tautomeric equation swings away from enol to keto form. Less water soluble. Can crystallise in small vessels causing pain and ischaemia.
THIOPENTAL: ? Vd ? Clearance ? initial half life ? terminal half life
Vd - 2.4 L/kg
Clearance - 11 ml/min/kg
Half life - 8.5 mins
Terminal half life - 12 hours.
PROPOFOL:
- molecular structure
- stored form
Structure: phenolic derivative - 2,6 di-isopropylphenol
Presented as 1% or 2% lipid-water emulsion (soya bean/ purified egg phosphate). Poor solubility in water.
PROPOFOL:
- Uses
- Dose for induction
- Plasma conc for maintenance
Used for induction and maintenance of GA.
Sedation of ventilated patients in ITU.
Induction dose: 1-2 mg/kg,
Plasma conc: 4-8 micrograms/ ml will maintain anaesthesia.
PROPOFOL:
? Systemic effects
- HR, Contractility, SVR, MAP, RESP, CBF
? GI effects
? Metabolic effects
?Miscellaneous
Systemic: Depression of all systems except HR remains stable. May become bradycardic with concurrent use of opioids.
GI - some evidence of antiemetic properties
Metabolic - fat overload syndrome with prolonged infusion, fatty infiltration of liver, kidneys, heart and lungs.
Miscellaneous - pain on injection, and can turn urine and hair green.
PROPOFOL: Kinetics
? Vd
? Clearance
? Protein binding %
Vd - 4L
Clearance - 25 ml/min/kg
98% protein bound
PROPOFOL: Kinetics ? pKa ? % unionised at physiological pH ? initial half life ? terminal half life
Weak organic acid
pKa - 11
Fully unionised at pH 7.4
Half life - 2 mins
Terminal half life - 4-7 hours
KETAMINE:
? molecular form
? storage form
- phencyclidine derivative
- presented as a racemic mixture OR as a single S+ enantiomer which is 2-3 x potent the R- enantiomer.
- Acidic solution pH 3.5-5.5, water soluble.
- Concentrations available: 10, 50, 100 mg/ml
KETAMINE: Dosing
? IV induction
? IM induction
? Other routes that can be used
IV dose - 1-2 mg/kg
IM dose - 5-10mg/kg
Other routes: PO, PR, Intrathecal and epidural.
KETAMINE: Systemic effects
- HR, Contractility, SVR, MAP, Resp summary
- CNS Specific effects
- Uniquely causes sympathetic stimulation therefore increases HR, Contractility, SVR, MAP, CBF and causes bronchodilation. Increased muscle tone may cause airway difficulty/ jerking movement of limbs.
Specific CNS effects:
- dissociative anaesthesia
- intense analgesia and amnesia
- Does not produce anaesthesia in one-arm-brain cycle, it takes 90 seconds
- Hallucinations, delirium post op
- Emergence phenomena less common in young and elderly. (maybe reduced by using benzo/opioids)
KETAMINE: Cardiac effects
? differences in Racemix mixture use.
- Sympathetic stimulation increases circulating Adrenaline and Noradrenaline.
Increasing CO, HR, BP and myocardial O2 demand. - Racemic mixture- mild myocardial depression, more from S+
- Racemic mixture blocks ATP-sensitive potassium channels, key mechanism of myocardial pre-conditioning - `R+ enantiomer
S+ alone does not do this.
