Operol Mechanism of Action

Pharmacology: Propofol injectable emulsion is an intravenous sedative-hypnotic agent for use in the induction and maintenance of anesthesia or sedation. Intravenous injection of a therapeutic dose of Propofol induces hypnosis, with minimal excitation, usually within 40 seconds from the start of injection (the time for one arm-brain circulation). As with other rapidly acting intravenous anesthetic agents, the half-time of the blood-brain equilibrium is approximately 1 to 3 minutes, accounting for the rate of induction of anesthesia.
Pharmacodynamics: Pharmacodynamic properties of Propofol are dependent upon the therapeutic blood Propofol concentrations. Steady-state Propofol blood concentrations are generally proportional to infusion rates. Undesirable effects such as cardio respiratory depression, are likely to occur at higher blood concentrations which result from bolus dosing or rapid increases in infusion rates. An adequate interval (3-5 minutes) must be allowed between dose adjustments in order to asses clinical effects.
The hemodynamic effect of Propofol injectable emulsion during induction of anesthesia vary. If spontaneous ventilation is maintained, the major cardiovascular effect is arterial hypotension (sometimes greater than a 30% decrease) with little or no change in heart rate and appreciable decrease in cardiac output. If ventilation is assisted or controlled (positive pressure ventilation), there is an increase in the incidence and the degree of depression of cardiac output. Addition of an opioid, used as a premedicant, further decreases cardiac output and respiratory drive. If anesthesia is continued by infusion of Propofol injectable emulsion, the stimulation of endotracheal intubation and surgery may return arterial pressure towards normal. However, cardiac output may remain depressed. Comparative clinical studies have shown that hemodynamic effects of Propofol injectable emulsion during induction of anesthesia are generally more pronounced than with other intravenous (IV) induction agents.
Induction of anesthesia with Propofol injectable emulsions frequently associated with apnea in both adults and pediatric patients.
During maintenance of general anesthesia, Propofol injectable emulsion causes a decrease in spontaneous minute ventilation usually associated with an increase in carbon dioxide tension which may be marked depending upon the rate of administration and concurrent use of other medication (e.g, opioid, sedatives. etc).
During monitored anesthesia care (MAC) sedation, attention must be given to the cardiorespiratory effects of Propofol injectable emulsion. Hypotension, oxyhemoglobin, desaturation, apnea, and airway obstruction can occur, especially following a rapid bolus of Propofol injectable emulsion. During initiation of MAC sedation, slow infusion or slow injection techniques are preferable over rapid bolus administration. During maintenance of MAC sedation, a variable rate infusion is preferable over intermittent bolus administration in order to minimize undesirable cardio respiratory effects in the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation.
Pharmacokinetics: The pharmacokinetics of Propofol are well-described by a three compartment linear model with compartments representing the plasma, rapidly equilibrating tissues, and slowly equilibrating tissues.
Following an IV bolus dose, there is rapid equilibrium between the plasma and the brain, accounting for the rapid onset of anesthesia. Plasma levels initially decline rapidly as a result of both distribution and metabolic clearance. Distribution accounts for about half of this decline following a bolus of Propofol. However, distribution is not constant over time but decreases as body tissues equilibrate with plasma and become saturated. The rate at which equilibrium occurs is a function of the rate and duration of the infusion. When equilibrium occurs there is no longer a net transfer of Propofol between tissues and plasma.
Discontinuation of the recommended doses of Propofol injectable emulsion after the maintenance of anesthesia for approximately one hour, or for sedation in the ICU for one day, results in a prompt decrease in blood Propofol concentrations and rapid awakening. Longer infusions (10 days of ICU sedation) results in accumulaton of significant tissue stores of Propofol, such that the reduction in circulating Propofol is slowed and the time to awakening is increased.
Propofol clearance ranges from 23-50 mL/kg/min (1.6 to 3.4 L/min in 70 kg adults). It is chiefly eliminated by hepatic conjugation to inactive metabolites which are excreted by the kidney. A glucuronide conjugate accounts for about 50% of the administered dose. Propofol has a steady state volume of distribution (10 day infusion) approaching 60 L/kg in healthy adults. A difference in pharmacokinetics due to gender has not been observed. The terminal half-life of Propofol after a 10-day infusion is 1 to 3 days. The clearance of Propofol in the children was similar to adults.