Disoprofol

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

If overdosage occurs, Propofol administration should be discontinued immediately. Overdosage is likely to cause cardiorespiratory depression. Respiratory depression should be treated by artificial ventilation with oxygen. Cardiovascular depression may require repositioning of the patient by raising the patient's legs, increasing the flow rate of intravenous fluids, and administering pressor agents and/or anticholinergic agents. (L1712)

Mild myoclonic movements are common, as with other intravenous hypnotic agents. Another recently described rare, but serious, side effect is propofol infusion syndrome. This potentially lethal metabolic derangement has been reported in critically-ill patients after a prolonged infusion of high-dose propofol in combination with catecholamines and/or corticosteroids. Overdose of these agents is likely to cause cardiorespiratory depression. (L1002, L1160) They cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive. May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.

Liver test abnormalities are not common among patients during or after propofol anesthesia when given for a few hours. Indeed, propofol can be used safely in patients with cirrhosis and may be the preferred anesthetic agent in patients with minimal hepatic encephalopathy. However, isolated case reports of hepatitis arising within days or weeks after propofol anesthesia for minor procedures have been published. The pattern of serum enzyme elevations was usually hepatocellular and some instances were accompanied by jaundice and prolongation of prothrombin time activity (Case 1). Immunoallergic features and autoantibodies during the liver injury were absent. In most published instances, other diagnoses such as ischemic hepatitis and hepatitis C were not completely excluded.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2700(SRC), determined from a log Kow of 3.79(2) and a regression-derived equation(3), indicates that propofol is expected to have slight mobility in soil(SRC). Volatilization of propofol from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.1X10-6 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Propofol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.1X10-3 mm Hg(SRC), determined from a fragment constant method(5). Propofol may biodegrade in soil based on the biodegradability of the structurally similar compound, 2,6-dimethylphenol, which achieved 30-100 percent and 94 percent biodegradation in activated sludge screening tests after 14 days and 5 days, respectively(6,7).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2700(SRC), determined from a log Kow of 3.79(2) and a regression-derived equation(3), indicates that propofol is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 2.1X10-6 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 23 days and 170 days, respectively(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column. The volatilization half-life from a model pond is about 6.5 years when adsorption is considered(5). According to a classification scheme(6), an estimated BCF of 170(SRC), from an estimated log Kow(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is high(SRC). Propofol may biodegrade in the aquatic environment based on the biodegradability of the structurally similar compound, 2,6-dimethylphenol, which achieved 30-100 percent and 94 percent biodegradation in activated sludge screening tests after 14 days and 5 days, respectively(8,9).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), propofol, which has an estimated vapor pressure of 3.1X10-3 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase propofol is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 7.3 hrs(SRC), calculated from its rate constant of 5.3X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3).

Rapid - time to onset of unconsciousness is 15-30 seconds, due to rapid distribution from plasma to the CNS. Distribution is so rapid that peak plasma concentrations cannot be readily measured. Duration of action is 5-10 minutes. Parenteral (intravenous injection) (L1002); inhalation (L1002) ; dermal (L1002)

/Propofol/ ... injectable emulsion is not recommended for use in nursing mothers because /propofol/ ... injectable emulsion has been reported to be excreted in human milk and the effects of oral absorption of small amounts of propofol are not known.

Propofol Infusion Syndrome (PRIS): This is a rare but serious side effect of prolonged infusion of propofol (usually > 4mg/kg/hour for more than 24 hours). The syndrome presents as metabolic acidosis, hyperkalemia, hyperlipidemia, and rhabdomyolysis and may proceed to renal and cardiac failure and, ultimately, death.

The action of propofol involves a positive modulation of the inhibitory function of the neurotransmitter gama-aminobutyric acid (GABA) through GABA-A receptors.

Aside from the hypotension (mainly through vasodilatation) and transient apnea following induction doses, one of propofol's most frequent side effects is pain on injection, especially in smaller veins. A more serious but rare side effect is dystonia.

Propofol was detected in a 1,500 liter advanced waste treatment finished water sample taken in Pomona, California on September 25, 1974(1). Propofol was detected with one occurrence in over 4000 wastewater survey sample extracts during a chemical analysis program prescribed by the USEPA(2).

The Koc of propofol is estimated as 2700(SRC), using a log Kow of 3.79(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that propofol is expected to have slight mobility in soil.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl propofol, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Propofol injection. (a) Specifications. The drug is a sterile, nonpyrogenic, oil-in-water emulsion containing 10 milligrams of propofol per milliliter. ... (1) Dogs. (i) The drug is indicated for use as an anesthetic as follows: As a single injection to provide general anesthesia for procedures lasting up to 5 minutes; for induction and maintenance of general anesthesia using incremental doses to effect; for induction of general anesthesia where maintenance is provided by inhalant anesthetics. ... (2) Cats. (i) The drug is indicated for use as an anesthetic as follows: As a single injection to provide general anesthesia for short procedures, for induction and maintenance of general anesthesia using incremental doses to effect, and for induction of general anesthesia where maintenance is provided by inhalant anesthetics.

Medication

Use (kg; approx.) in Germany (2009): >5000

Its widespread use as an anesthetic induction agent has largely replaced that of sodium pentothal. It is also commonly used in veterinary medicine. (L1002). Used for induction and/or maintenance of anaesthesia and for management of refractory status epilepticus.

All Other Basic Organic Chemical Manufacturing

Phenol, 2,6-bis(1-methylethyl)-: ACTIVE