iv induction agent

1. DR ASHARAB TAD
DR P . N. JAIN

2. PROPOFOL INTRODUCED IN 1977 BY KAY & ROLLY
BASIC PHARMACOLOGY
It is one of the group of alkyl phenol.
The chemical structure is 2-6 di iso propyl phenol.
Propofol is insoluble in water and therfore initially prepared with cremaphor EL.
PH of 7, Pka of propofol in water is 11.
It is available as 1 % solution in 20 ml glasss ampoule or
vials and in 50, 100 ml pre filled syringes

3. Propofol consist of a phenol ring substituted with two Isopropyl
group is chemically described as
2,6- di isopropyl phenol
PHYSICOCHEMICAL CHARACTERISTICS

4. PREPARATIONS
Propofol administered intravenously as 1% solution in an aqueous solution of 10% soybean oil,
and 1.2% purified egg phospholipid added as emulsifier, with 2.25% of glycerol as a tonicity-
adjusting agent, and sodium hydroxide to change the pH
insoluble drug that requires a lipid vehicle for emulsification.
Current formulations of propofol use a soybean oil as the oil phase and egg lecithin as the
emulsifying agent that is composed of long chain triglycerides.4 This formulation supports
bacterial growth and causes increased plasma triglyceride concentrations when prolonged IV
infusions are used.
Propofol has a pH of 7 and appears as a slightly viscous, milky white substance

5. MECHANISM OF ACTION
GABA RECEPTOR COMPLEX
 Propofol is relatively selective modulator of GABA receptors
 g- amino butyric acid is inhibitory neurotransmitter in brain.
 Assemble to form cl- channel with GABA A receptor
Activation of GABA receptors increases transmembrane CL conductance
hyperpolarization of post synaptic membrane
functional inhibition of the postsynaptic neuron
Propofol decreases the rate of dissociation of GABA from its receptors, thereby increasing
the duration of the GABA –activated opening of chloride channel with resulting
hyperpolarisation of cell membrane.

6. GABA RECEPTOR: CONSISTS OF 5 SUBUNITS

7. PHARMACOKINETICS
 Clearance of propofol from the plasma exceeds hepatic blood
flow ,tissue uptake as well as hepatic oxidative metabolism by
cytochrome p450 removes the drug from plasma

8. Clinical uses
 Induction of anaesthesia: (1 to 2.5 mg/kg/ iv)
 Intravenous sedation: (25 to 75 micro g/kg/iv)
 Maintenance of Anaesthetic: (50 to 150 micro g/kg/iv)
 Day care surgery
 Antiemetic effect: (10 to 15 mf i.v)
 Sub hypnotic doses of propofol (10 to 15mg/IV) may be used in the post
anaesthesia care unit to treat nausea and vomiting. Very effective against
Chemotherapy-induced nausea and vomiting as it inhibits sub cortical pathways
 More effective than ondansetron in preventing postoperative nausea and
vomiting.
 Antipruritic Effect: propofol depress spinal cord activity
Propofol 10mg I.V is effective is the treatment of pruritis associated with Neuraxial opioid or cholestasis.
 ANTICONVULSANT ACTIVTY: 1 mg/kg iv decreases seizure duration.

9. CONTN…
Along with opioids it is agent of choice for total intravenous
anaesthesia [TIVA]
It can be used in icu for sedation.
It is the agent of choice for induction in susceptible individuals for
malignant hyperthermia

10. FOSPROPOFOL
Water soluble prodrug of propofol
Reduce the disadvantages of the lipid emulsion of propafol
Produces more complete amnesia and conscious sedation than midaz +fentanyl.
Slower onset and recovery than than propofol.

11. EFFECTS ON ORGAN SYSTEM
•Propofol decreases the cerebral metabolic rate for oxygen
(CMRO2)
•Decreasing the cerebral blood flow.
•Decreasing intracranial pressure.
•Decrease in early component of somato sensory and motor
evoked potential.
Central nervous
system
•Propofol decreases systemic blood pressure
•Hence adequate hydration before I.V administered of propofol
is recommended to minimize the blood pressure effect.
•inhibition of sympathetic vasoconstrictor nerve activity.—
vascular smooth muscle relaxation.
•negative inotropic effect of propofol results from decrease in
intracellular ca+ availability due to inhibition of trans
sarcolemmal ca+ influx
•Infusion of propofol causes decrease in myocardial blood flow
and oxygen consumption.
•Bradycardia and asystole
Cardiovascular
system

12. Respiration system:
Propofol produces does-dependent depression of ventilation with apnoea.
Maintenance infusion of propofol decreases tidal volume and frequency of
breathing.
It produces bronchodilation and decreases the incidence of intra-operative
wheezing in patients with asthma.
Propofol: Produces decrease in amplitudes of the early components of
somatosensory evoked potential.
Hepatic and Renal Function:
It does not affect hepatic and renal function.
Prolonged infusions of propofol have been associated with hepatocellular Injury
accompanied by lactic acidosis, bradysrhythmias, and rhabdomyolysis as part of
the propofol infusion syndrome
Prolonged infusion of propofol may result in excretion of green coloured urine,
which reflects, the presence of phenols in the urine.
Eye: Decreases the intraocular pressure occur immediately after induction.

13. CONTRAINDICATIONS

Hypersensitivity to propofol
injectable emulsion or any of its
components.
Allergies to eggs , eggs products ,
soybeans or soy products .

14. ADVANTAGES OVER THIOPENTONE
Rapid and smooth recovery
Complete elimination from body in 4 hrs so patient is ambulatory
early
Anti emetic
Antipruritic
Bronchodilator

15. Allergic Reactions:
Allergic components of propofol are phenyl nucleus and disopropyl side chain.
Pain on Injection:
It is the most common side effect associated with Propofol.
Using large veins and avoiding veins in the dorsum of the hand and adding
Lidocaine to the propofol solution reduce this.
Abuse potential:
Intense dreaming activity amorous behaviour and hallucinations has been seen
during recovery from the effects of propofol. Addiction is reported.
Bacterial Growth
Propofol strongly supports growth of Escherichia coli and pseudomonas
Aeruginosa.
Hypotension:
The most significant side effect on induction is the decrease in systemic blood
pressure.
Side Effect

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