Details About Overdose or Poisoning Generic Salt ::  Propofol

Propofol

    

Drug Pharmacology ::

I. Pharmacology./b>

   

Propofol(2,6-diisopropylphenol) is a sedative-hypnotic agent in a class ofalkyl phenol compounds. It is an oil at room temperature, is highlylipid soluble, and is administered as an emulsion. It is also anantioxidant, anticonvulsant, and anti-inflammatory agent; reducesintracranial pressure; and has bronchodilator properties. Propofol’ssite of action is at the GABAA receptor, where it activatesthe chloride channel. There may also be some action at the glutamateand glycine receptor sites. Propofol is an antagonist at the N-methyl-D-aspartate (NMDA) receptor. It is also an inhibitor of cytochrome P-450 enzymes.

On infusion, its effects are seen within less than 3 minutes and peak concentrations are reached in less than 20 minutes.

Itis highly protein bound, with a volume of distribution of 2–5 L/kgafter a single infusion and 25–60 L/kg after a continuous infusion oflonger than 7 days. Propofol has a high clearance rate estimated at1.5–2.2 L/min. This clearance rate exceeds hepatic blood flow andsuggests extrahepatic metabolism.

 Propofolis metabolized rapidly in the liver by conjugation to glucuronide andsulfate intermediates that are water soluble and inactive. This occurspredominantly via oxidation by cytochrome P-450 2B6. P-450 isoforms2A6, 2C8, 2C18, 2C19, and 1A2 are also involved in its metabolism to alesser extent. There is minimal enterohepatic circulation, and lessthan 1% is excreted unchanged.

Drug Indications ::

Indications

   

Propofolis most useful when the goal of anesthesia or sedation is rapidinduction and recovery. It can be used for the induction andmaintenance of anesthesia.

Propofolis useful in the intensive care unit for sedation of mechanicallyventilated patients, especially patients with severe head injuries. Itmay also be beneficial for conscious sedation in certain settings.

Propofolmay be effective as an adjunct anesthetic agent for refractory alcoholor other sedative-hypnotic withdrawal syndromes (such as GHB andbarbiturates) and can also be used to treat status epilepticus.

Propofol has been used in rapid opiate detoxification protocols.

Drug Contra-Indications ::

III. Contraindications./b>

   

Notapproved for pediatric patients less than 3 years of age who requiresedation for mechanical ventilation. Several deaths have been reportedwhen propofol was used in this setting.

Itmay be contraindicated for patients with seizure disorders (risk ofseizures while weaning from therapy) and those with underlyinghyperlipidemic states.

Hypersensitivity to propofol or additives such as sulfites and allergy to soybean or eggs.

Drug Adverse Effects ::

IV. Adverse effects

   

Pain at the injection site can occur (use larger veins or premedicate with lidocaine).

Hypotension, bradycardia, supraventricular tachydysrhythmias, conduction disturbances, cough, and bronchospasm may occur.

Rapidinfusion rates and anesthetic doses require respiratory support. Avoidrapid bolus doses in the elderly because of the higher risk ofhypotension, bradycardia, apnea, and airway obstruction.

Anestheticdoses may be associated with myoclonus, posturing, and seizure-likemovement phenomena (jerking, thrashing). Seizures have been noted whenpatients were weaned from propofol. Allergic reactions to metabisulfiteare possible. Bacterial infections have also been noted.

E. Propofol infusion syndrome,a condition of lactic acidosis, renal failure, rhabdomyolysis, andcardiovascular collapse, has been reported after prolonged high-doseinfusion in both pediatric and adult populations. Prolonged use (>48 hours), infusion rates greater than 5mg/kg/h, and concomitantcatecholamine administration (with or without steroids) have beenimplicated as risk factors.

F. Acute pancreatitis with single or prolonged use can occur. Hyperlipidemia can also occur after prolonged use.

G. Though it is not thought of as a drug of abuse, propofol abuse has been reported.

H. Urine may be discolored green or dark green.

Use in pregnancy. FDA category B. Propofol crosses the placenta and may be associated with neonatal CNS depression (see Table III–1).

Drug Lab Interactions ::

Drug or laboratory interactions

   

Anadditive effect with other CNS depressants may result in lower propofoldosage requirements if given concomitantly. Through its inhibition ofcytochrome P-450 2C9, 2D6, and 3A4, propofol may increase levels ofmidazolam, diazepam, and other opiates such as sufentanyl andalfentanyl, causing respiratory depression, bradycardia, andhypotension.

Propofol levels may be increased by lidocaine, bupivacaine, and halothane, producing an increased hypnotic effect.

Concurrent use with succinylcholine may result in bradycardia.

Drug Dose Management ::

Dosage and method of administration. Propofol currently is administered as an intravenous medication only, and the dosage must be individualized and titrated.

   

For induction anesthesia,give 1–2.5 mg/kg (slow infusion rate of about 40 mg every 10 seconds).If titrating with intermittent bolus doses (usually 40-mg increments),allow approximately 2 minutes for peak effect. In pediatric patients (3to 16 years of age), give 2.5–3.5mg/kg over 20–30 seconds. Formaintenance anesthesia, the dose should be titrated between 50 and 150mcg/kg/min (or 3–9 mg/kg/h) and may be supplemented with intermittentbolus doses of 25–50 mg. Healthy pediatric patients (2 months–16 years)have been administered continuous infusion doses ranging between 7.5–18mg/kg/h. After initial induction dose, may require a higher continuousinfusion dose of up to 200 mcg/kg/min (or 12 mg/kg/h) for the first10–15 minutes.

For sedation,use a lower dosage range of 25–75 mcg/kg/min (or 1.5–4.5 mg/kg/h) ortitrate with intermittent bolus doses of 10–20 mg, then maintain with25–50 mcg/kg/min (or 1.5–3 mg/kg/h).

Pediatricpatients may require a higher dose: 2.5–3.5 mg/kg induction dose,followed immediately by 200–300 mcg/kg/min (or 12–18 mg/kg/h) for about30 minutes, then 125–150 mcg/kg/min (or 7.5–9 mg/kg/h).

Forpatients older than 60 years of age, a lower induction dose of 1–1.5mg/kg (infuse about 20 mg every 10 seconds) is recommended.

E.For rapid opiate detoxification, patients are given 2–4 mg/kg (or 6mg/kg/h with intermittent bolus doses of 0.3–0.5 mg/kg) followed bymaintenance of 3.5–6 mg/kg/h (usually for 5–8 hours). This is coupledwith a neuromuscular blocker, and an opiate antagonist (naloxone ornaltrexone) is administered after anesthesia is achieved.

Drug Chemical Formulations ::

Formulations

   

Parenteral. Propofol(Diprivan) 1% (10 mg/mL) emulsion in 10% soybean oil with 2.25%glycerol and 1.25% purified egg phospholipid in 20-, 50-, or 100-mLvials and a 50-mL prefilled syringe. Contains disodium EDTA or sodiummetabisulfite as a preservative. A 2% (20 mg/mL) emulsion has beenformulated to provide the same amount of drug with less lipidconcentration but has not been approved in the United States. Note: Propofol is provided as a ready- to-use preparation, but if dilution is necessary, use only D5W and do not dilute to concentrations less than 2 mg/mL.

The suggested minimum stocking level to treat a 70-kg adult for the first 24 hours is 2.5 g (provides anesthesia for a 6-hour interval).

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