PROPOFOL
INTRODUCTION
Propofol is an intravenous sedative-hypnotic agent used in the induction and maintenance of general anesthesia.
Propofol is an alkyl phenol derivative. It was discovered in the 1980s by John B. (Iain) Glen and was first time used clinically in 1986. the chemical structure of propofol is 2,6 di isopropyl phenol.
Propofol achieved great popularity in the practice of anesthesia because of its safety, rapid recovery, and antiemetic property.
PHYSICAL PROPERTIES OF PROPOFOL
Propofol is a white emulsion liquid that is soluble in lipids but only a water-soluble formulation is slightly soluble in water.
The formulation of propofol contains some active ingredients like:
a) Soyabean oil (for stability)
b) Glycerol (for isotonicity)
c) Egg lecithin (extracted from egg yolk)
d) Disodium edetate 0.005% and sodium metabisulfite 0.025% (to help in the control of the growth of microorganisms in the drug)
e) Sodium hydroxide (to adjust the PH of the solution)
NATURE AND PH OF SOLUTION
Propofol is isotonic in nature with a PH value of 7–8.5.
AVAILABILITY
Propofol is available in multiple vials like:
200mg/20ml
500mg/ml
0.5% is also available
DOSES OF THE DRUG
Different doses of propofol are considered depending on the age and physical status of the patient:
a) Normal adult dose > 1.5–2.5 mg/kg
b) Elderly dose > 1.2 mg/kg
c) children > 3–3.5 mg/kg
d) For sedation in ICU > 50–100 micrograms/mint.
MECHANISM OF ACTION
Propofol allosterically increases the binding affinity of GABA (gamma-aminobutyric acid) to GABA-a receptor in CNS which is coupled to a chloride channel and cause it causes the activation of GABA-a receptor which leads to hyperpolarization of nerve membrane thus causing sedation and hypnosis.
PHARMACOKINETICS
After a single bolus dose of propofol, blood propofol level decreases rapidly because of redistribution and elimination of propofol rapidly in the human body.
ONSET OF PROPOFOL
The onset of propofol is rapid with time <40 seconds and a peak effect of about 100 seconds.
AWAKENING
Awakening is also very rapid and is about 10–15 minutes due to the very short distribution half-life.
ELIMINATION HALF LIFE
The elimination half-life of propofol is 3–7 hours, although its effective half-life is much shorter which is 30–60 minutes.
Propofol is oxidized to 1,4 diisopropyl quinol in the liver, although metabolites of propofol are primarily excreted through urine.
PHARMACODYNAMICS
CENTRAL NERVOUS SYSTEM
Propofol decreases intracranial pressure (ICP), cerebral blood flow, and cerebral blood volume.
Propofol has antipuritic and anti convulsant properties.
It has been used successfully to terminate status epilepticus and is safe to administer to an epileptic patient.
It decreases intraocular pressure (IOP).
CARDIOVASCULAR
The major cardiovascular effect of propofol is that it causes a decrease in arterial blood pressure due to a drop in systemic vascular resistance, preload, afterload, and cardiac contractility.
It also causes hypotension due to induction which is reversed by laryngoscopy and intubation.
It also decreases myocardial oxygen consumption and coronary blood flow.
Propofol markedly impairs the normal arterial baroreflex response to hypotension.
RESPIRATORY
Propofol is a respiratory depressant and causes apnea after induction, and also depresses the normal response to hypercarbia.
It causes the impression of laryngeal reflexes which results in a low incidence of coughing or laryngospasm.
Propofol can cause histamine release which causes a lower incidence of wheezing.
HEPATORENAL
There is a transient decrease in renal function and hepatic blood flow is been reduced due to a reduction in cardiac output and arterial pressure.
Vasoconstriction of splanchnic and renal blood vessels which causes a decrease in renal blood flow and GFR.
SPECIAL CONSIDERATION FOR PROPOFOL
It supports bacterial growth like E.Coli and Pseudomonas.
An aseptic technique should be used before administration.
It causes pain on injection, so for that purpose 2ml lidocaine of 1% should be administered prior to the injection or can be mixed with the formulation of propofol.
Propofol should be administered within 6 hours of opening the ampule otherwise it would be considered expired.
SIDE EFFECTS
Pain on injection
Bradycardia
Hypertriglyceridemia
Allergic reaction
Lactic acidosis
Green color urine due to (prolonged infusion)
Bacterial growth.
