ANESTESI

INTRAVENOUS ANESTHETICS

PROPOFOL
- Most used IV hypnotic
- Sediaan: 10 mg/ml
- Dosis induksi:
o Adults: 1-2.5 mg/kg
o Elders: 1 mg/kg (with premedication) to 1.75 mg/kg (without premedication
o Premedication w/ an opiate or benzo or both markedly reduces the necessary
induction dose
- Infusion rate: 100-200 μg/kg/min
- Injection speed
- Onset of action: 15-20 seconds
- Durasi kerja: duration of hypnosis is dose-dependent, being 5-10 mins after 2-2.5 mg/kg.
- Half-life: 4-7 h
- Clearance rate: >1.5 L/min
- Cara kerja:
o The hypnotic action of propofol is mostly mediated by enhancing γ-aminobutyric
acid (GABA)-induced chloride current through its binding to the β-subunit of
GABAA receptor.
 o The effect of propofol has been described in two manners—indirect and direct.
Propofol exhibits an indirect effect by potentiation of the ion channel activation
by GABA, shifting the concen- tration-response relationship to the left. At higher
propofol concentrations, propofol is also thought to directly activate GABA A
receptor channels.
o Propofol results also in widespread inhibition of the N-methyl-d-aspartate
(NMDA) subtype of glutamate receptor through modulation of sodium channel
gating, an action that also may contribute to the drug’s CNS effects.
- Used for induction, maintenance of anesthesia, and for sedation in and outside the OR.
- Metabolised mainly in the liver, and also kidney and lungs.
- ES: hemodynamic depressant effects, reduces hepatic blood flow (hence may reduce the
clearance of other drugs metabolized by the liver), decreases ICP in patients with normal
or increased ICP, hallucinations, sexual fantasies, opisthotonos, pain on injection, apnea,
myoclonus, hypotension, thrombophlebitis of the vein injected into (rare),
bronchodilation in COPD, affects fetal brain development in pregnant patients, propofol
infusion syndrome (rare)
- Benefits: quick recovery time, bersifat neuroprotektif (like most anesthetics, tpi sbtlnya
efek neuroprotektif propofol msh kontroversial), decreases ICP, decreases IOP (better
than thiopental in preventing IOP increase after succinylcholine or ETT), anti-tumor
effect
- Blood propofol concentrations increase in the presence of shock.
- Propofol adlh sebuah CYP3A4 inhibitor  competitive inhibition of CYP activity with
midazolam

- Midazolam affects the pharmacokinetics of propofol.52 In the presence of a sedative

midazolam concentration of 200 ng/mL, the blood propofol concentrations become
elevated by about 25%. Midazolam reduces propofol metabolic clear- ance from 1.94 to
1.61 L/min, Cl2 from 2.86 to 1.52 L/ min, and Cl3 from 0.95 to 0.73 L/min. The high
extraction ratio of propofol of 0.79 to 0.92 suggests that the metabolic clearance of
propofol may not be affected by enzyme inhibi- tion but may be susceptible to changes
in hepatic perfusion. The changes in the pharmacokinetics of propofol induced by
midazolam thus may be the result of the hemodynamic alterations induced by the
coadministration of midazolam.
- Propofol in its turn affects midazolam pharmacokinetics as well.20 In the presence of
sedative concentrations of pro- pofol, plasma midazolam concentrations increased by
27%. In the presence of propofol, midazolam is administered in a smaller central
compartment from which midazolam is cleared and distributed less rapidly to peripheral
tissues. For example, alfentanil53 has been shown to increase blood pro- pofol
concentrations through a reduction in the elimination and distribution clearance of
propofol. This is in line with other pharmacokinetic interactions between hypnotics and
opioids when combined with propofol. Propofol has been shown to increase alfentanil
concentrations by decreasing the elimination and the rapid and slow distribution clear-
ances of alfentanil. Coadministration of propofol increased remifentanil concentrations
 via both a decrease in the cen- tral volume of distribution and distributional clearance of
remifentanil by 41% and elimination clearance by 15%. Propofol kinetics is unaltered by
renal disease.
- Bersifat adiktif

BARBITURAT
- Metabolized hepatically (except phenobarbital)
- Cara kerja: (1) enhancement of the synaptic actions of inhibitory neurotransmitters, and (2) blockade of
the synaptic actions of excitatory neurotransmitters.
-

NOTES

- Anesthetics are neuroprotective because they reduce the metabolic oxygen use that is
beneficial for the balance between energy supply and demand and because they
increase the tolerance to hypoxia by the neuronal tis- sue.

INHALATION ANESTHESIA
- Sevoflurane, desflurane, isoflurane  agen induksi inhalasi yg plg sering digunakan
-