Thiopental Propofol Etomidate Midazolam Ketamine
-Sulfur barbiturate Propofol -Imidazole-carboxy -pKa: 6.15 -Phencycline derivative
-pKa 7.6 largely non-ionized at -fat-soluble / pKa = 11 derivative -96% albumin binding -Containing a racemic mixture of
physiological pH - albumin binding # 98 pKa = 4.24 -fat-soluble two isomers
- water-soluble in salt form Diprivan: -Sparingly soluble in water Activation of the GABA-A -pKa: 7.5
-Dissolvable powder (water or Lipid emulsion 10mg/ml solubilized in propylene receptor -Weak protein binding
Physico-
chemical NaCl but not Ringer lactate) Isotonic - neutral pH glycol or intralipid -Highly lipid-soluble
properties -pH >10 : Do not freeze
⬥ risk of tissue necrosis Do not use antibacterial filter Activation of the GABA-A
⬥ precipitation with acid Activation of the GABA-A receptor
solutions (curares) receptor
⬥ bacteriostatic
activation of GABA-A
receptors
-Saturable albumin binding at -Large and fast distribution -Large and fast distribution Vss # 100 L -Pharmacokinetics similar to
high concentrations (bolus -Metabolic clearance # 2 l/min -Metabolic clearance 1.2 -Metabolic clearance # 0.5 those of thiopental
effect) (Conjugation, mainly / No l/min hepatic blood flow l/min (intermediate) -Short duration of action -Highly
active metabolite) -Hydrolyzed by hepatic -Cytochrome P450 and lipid-soluble
-Rapid transfer to site of action
-No accumulation esterases conjugation -Active -Accumulates on reinjection
/ rapid initial distribution -Linear pharmacokinetics in -No active metabolite metabolite may pose -Metabolized by the cytochrome
-> Rapid, brief effect of a single anesthetic concentration -No accumulation problems during prolonged P450 pathway
Pharmaco- dose ranges -Linear pharmacokinetics sedation in intensive care. -Norketamine 3 times less potent
kinetics -Metabolic clearance250ml/min in anesthetic concentration -50% hepatic first-pass effect.
-oxidation by cytochromesP450 ranges -Long onset of action
-No active metabolite (several minutes) and
prolonged effect (90 minutes
-Accumulation on reinjection or
after a single dose)
infusion Inter-individual variability +++
Cannot be used for anesthesia
maintenance
pharmaco- -Reduction of metabolic needs of -Reduction of metabolic -Reduce metabolic needs Reduction in the brain's ketamine causes ;
dynamics: the brain needs of the brain of the brain metabolic requirements DISSOCIATIVE anesthesia
Effects on -Decrease cerebral blood flow -Decrease cerebral blood -Decrease cerebral blood - Decrease in DSC, while -EEG: dissociation between
C.N.S flow, self-regulation flow, self-regulation self-regulation is maintained thalamocortical and limbic
-Decrease in ICP
maintained maintained - Decrease in ICP systems.
- Anticonvulsant -reduction of ICP -Decrease in ICP - Anticonvulsant -Cataleptic-like state: eyes open
-Anticonvulsant -Specific cerebral + slow nystagmus, muscular
-Abnormal movements protection mechanism at Currently used more as an hypertonia -Non-competitive
through subcortical release cellular level anxiolytic and amnestic inhibition at NMDA receptors.
-Subcortical release of than as a hypnotic -Psychodysleptic effects include
abnormal movements visual and auditory disturbances,
mood and body image changes,
hallucinations and decorporation.
-Ketamine has a powerful
anti-convulsant effect
-Dose-dependent depression of -Drop in blood pressure on -Minimal hemodynamic -Drop in blood pressure due -Stimulation of the cardiovascular
myocardial contractility induction due mainly to effects, not enhanced in to arterial and venous system: increase in heart rate,
-vasodilation, but little change in arterial and venous pathological myocardium vasodilation blood pressure, cardiac output,
vasodilation +++. -Poorly tolerated in coronary blood flow and O2
SVRs
-Very poorly tolerated in -Improves the balance hypovolemia consumption. Due to stimulation
-decrease in arterial pressure hypovolemia between myocardial oxygen -Associated baroreflex of sympathetic centers with
and cardiac output -Associated baroreflex supply and demand depression: little tachycardia increased catecholamines
Hemodynamic -frequent tachycardia (30%) depression: no tachycardia -Does not prevent -Preserves autoregulation of
effects →myocardial oxygen -Action on whole-heart sympathetic response to coronary circulation
consumption myocardial contractility still intubation →combine with
-can be very poorly tolerated in debated morphine +++
-During anesthesia
cases of hypovolemia or
maintenance at therapeutic
decompensated heart disease. [ ], blood pressure does not
decrease with increasing
concentrations.
-Transient apnea during bolus -Concentration-dependent -Less respiratory depression-Concentration-dependent Slightly depresses ventilation
induction respiratory depression, but than thiopental or propofol respiratory depression, but -Preserves muscle tone and
-Persistent depression of allows maintenance of -May cause hiccups or allows maintenance of pharyngolaryngeal reflexes
spontaneous ventilation. coughing spontaneous ventilation. -Induces salivary and bronchial
ventilatory control
-Transient apnea during -Transient apnea during hypersecretion -bronchodilator
-Very moderate depression of bolus induction bolus induction, initially - Lastly, it is not histaminolytic,
Respiratory
glottic reflexes -Depression of glottic central, then obstructive and allergic reactions are rare.
effects
→ does not allow intubation reflexes (importance +++ because of
without curares at usual doses -Preservation of hypoxic prolonged effect and
pulmonary vasoconstriction frequent use without airway
-Bronchodilator control)
Contraindicated in porphyria -Pain on injection (prevented Pain on injection +++ (more -Very few intrinsic side effects -Increased salivary secretion
-Extravascular administration by co-administration of frequent than with propofol) -Accidents sometimes fatal -Psychodysleptic manifestations
leads to tissue necrosis lidocaine 0.1 mg/kg) -Myoclonus frequent in due to ignorance of midazolam-Coughing, hiccups
-Rare anaphylactic reaction young, non-pre-medicated pharmacology : -Nausea-vomiting: rare
-Intra-arterial administration leads
-Transmission of pathogens patients Prolonged residual
to spasm +++ and downstream -Nausea and vomiting (30 drowsiness
Undesirable
ischemia to 40% of cases, more if Obstructive apneas
effects
- Anaphylaxis exceptional associated with morphine) Relative overdosage (elderly
-Inhibits adrenocortical subjects +++)
secretion -All the more serious when
-Anaphylactic reaction midazolam is used for
very rare ambulatory sedation
only for induction : Induction: Dosage: Dosage
Adults: 3–5 mg/kg. • Adult: 2–3 mg/kg Adult: 0.2-0.4 mg/kg - premedication :
Children: 5–7 mg/kg • Child: 2.5–5.0 mg/kg -rectal 0.3mg/kg
• Elderly: 1–2 mg/kg -oral 0.5mg/kg (children)
use -oral 10-15mg (adult)
■ Maintenance of anesthesia: - sedation: 0.1-0.2 mg/kg/IV
3–12 mg/kg/h
■ Sedation: 2–6 mg/kg/h
-Anti-emetic -Centrally-induced muscle -No uterine atony
-Anti-oxidant (structural relaxant effect -Increased IOP
analogue of vitamin E) -Can be used in subjects -No tongue drop
-Can be used in subjects susceptible to malignant -Diffuse muscular -hypertonia
other effects susceptible to malignant hyperthermia -hyperglycemia
hyperthermia -Can be used to anesthetize
-Suitable for all asymptomatic porphyric patients
hepatic porphyrias
