Faculty of Physical Therapy

Propofol

Under Supervision of

Prof. Ramadan A. M Hemeida

Dr. Remon Roshdy Rofaeil

Dr. Ali Khames

Dr. Mohammed Nabil

Prepared by

Tomas Samir Fathy

2190091
 Contents
Introduction ...................................................... 3
Mechanism of action ........................................ 4
Pharmacodynamics .......................................... 4
Pharmacokinetics ............................................. 5
Pharmacological Effects .................................. 7
Therapeutic Use................................................ 8
Contraindications: ........................................... 9
Adverse Effect : ................................................ 9
Drug Interaction : .......................................... 10
Dosage and Administration ........................... 11
Product in the Market ................................... 13

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Introduction
Propofol, marketed as Propofol, among other names, is a short-
acting medication that results in a decreased level of
consciousness and a lack of memory for events. It is given by
injection into a vein, and the maximum effect takes about two
minutes to occur and typically lasts five to ten minutes.
Propofol is an intravenous anaesthetic agent used for induction
and maintenance of general anaesthesia. IV administration of
propfol is used to induce unconsciousness after which anaesthesia
may be maintained using a combination of medications.
Recovery from propofol-induced anaesthesia is generally rapid
and associated with less frequent side effects (e.g. drowsiness,
nausea, vomiting) than with thiopental, methohexital, and
etomidate. Propofol may be used prior to diagnostic procedures
requiring anaesthesia, in the management of refractory status
epilepticus, and for induction and/or maintenance of anaesthesia
prior to and during surgeries.
Structure

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

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 side effects, such as cardiorespiratory depression, are
likely to occur at higher blood concentrations which result from
bolus dosing or rapid increases in infusion rates. An adequate
interval (3 to 5 minutes) must be allowed between dose
adjustments in order to assess clinical effects.
The hemodynamic effects 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 no 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
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may return arterial pressure towards normal. However, cardiac
output may remain depressed. Comparative clinical studies have
shown that the 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 Emulsion is
frequently associated with apnea in both adults and pediatric
patients. In adult patients who received PROPOFOL Injectable
Emulsion (2 to 2.5 mg/kg), apnea lasted less than 30 seconds in
7% of patients, 30 to 60 seconds in 24% of patients, and more
than 60 seconds in 12% of patients. In pediatric patients from
birth through 16 years of age assessable for apnea who received
bolus doses of PROPOFOL Injectable Emulsion (1 to 3.6 mg/kg),
apnea lasted less than 30 seconds in 12% of patients, 30 to 60
seconds in 10% of patients, and more than 60 seconds in 5% of
patients.

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 equilibration between

the plasma and the brain, accounting for the rapid onset of
anesthesia. Plasma levels initially decline rapidly as a result of

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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 equilibration occurs is a function of the rate and
duration of the infusion. When equilibration 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)
result in accumulation of significant tissue stores of propofol,
such that the reduction in circulating propofol is slowed and the
time to awakening is increased.

By daily titration of PROPOFOL Injectable Emulsion dosage to

achieve only the minimum effective therapeutic concentration,
rapid awakening within 10 to 15 minutes can occur even after
long-term administration. If, however, higher than necessary
infusion levels have been maintained for a long time, propofol
redistribution from fat and muscle to the plasma can be significant
and slow recovery.

The figure below illustrates the fall of plasma propofol levels

following infusions of various durations to provide ICU sedation.

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Pharmacological Effects
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
equilibration is approximately 1 to 3 minutes, accounting for the
rate of induction of anesthesia. The mechanism of action, like all
general anesthetics, is poorly understood. However, propofol is
thought to produce its sedative/anesthetic effects by the positive
modulation of the inhibitory function of
the neurotransmitter GABA through the ligand-gated GABAa
receptors.

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Therapeutic Use
Propofol (propofol) Injectable Emulsion is a sedative-hypnotic
agent used to help you relax before and during
general anesthesia for surgery or other medical procedure. It is
also used in critically ill patients who require a breathing tube
connected to a ventilator. Propofol is available in generic form.
Indications
PROPOFOL Injectable Emulsion is an IV sedative-hypnotic
agent that can be used as described in the table below.
Safety, effectiveness and dosing guidelines for PROPOFOL
Injectable Emulsion have not been established for MAC Sedation
in the pediatric population; therefore, it is not recommended for
this
PROPOFOL Injectable Emulsion is not recommended for
induction of anesthesia below the age of 3 years or for
maintenance of anesthesia below the age of 2 months because its
safety and effectiveness have not been established in those
populations.
In the Intensive Care Unit (ICU), PROPOFOL Injectable
Emulsion can be administered to intubated, mechanically
ventilated adult patients to provide continuous sedation and
control of stress responses only by persons skilled in the medical
management of critically ill patients and trained
in cardiovascular resuscitation and airway management.

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PROPOFOL Injectable Emulsion is not indicated for use in
Pediatric ICU sedation since the safety of this regimen has not
been established

Contraindications:
PROPOFOL Injectable Emulsion is contraindicated in patients
with a known hypersensitivity to propofol or any of PROPOFOL
Injectable Emulsion components.
PROPOFOL Injectable Emulsion is contraindicated in patients
with allergies to eggs, egg products, soybeans or soy products.

Adverse Effect :
One of propofol's most common side effects is pain on injection,
especially in smaller veins. This pain arises from activation of the
pain receptor, TRPA1, found on sensory nerves and can be
mitigated by pretreatment with lidocaine. Less pain is
experienced when infused at a slower rate in a large vein
(antecubital fossa). Patients show considerable variability in their
response to propofol, at times showing profound sedation with
small doses.
Additional side effects include low blood pressure related to
vasodilation, transient apnea following induction doses, and
cerebrovascular effects. Propofol has more pronounced
hemodynamic effects relative to many intravenous anesthetic
agents.[44] Reports of blood pressure drops of 30% or more are
thought to be at least partially due to inhibition of sympathetic

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nerve activity. This effect is related to the dose and rate of
propofol administration. It may also be potentiated by opioid
analgesics. Propofol can also cause decreased systemic vascular
resistance, myocardial blood flow, and oxygen consumption,
possibly through direct vasodilation. There are also reports that it
may cause green discolouration of the urine.

Drug Interaction :
The induction dose requirements of PROPOFOL Injectable
Emulsion may be reduced in patients with intramuscular or
intravenous premedication, particularly with narcotics
(e.g., morphine, meperidine, and fentanyl, etc.) and combinations
of opioids and sedatives (e.g., benzodiazepines,
barbiturates, chloral hydrate, droperidol, etc.). These agents may
increase the anesthetic or sedative effects of PROPOFOL
Injectable Emulsion and may also result in more pronounced
decreases in systolic, diastolic, and mean arterial pressures
and cardiac output.
During maintenance of anesthesia or sedation, the rate of
PROPOFOL Injectable Emulsion administration should be
adjusted according to the desired level of anesthesia or sedation
and may be reduced in the presence of
supplemental analgesic agents (e.g., nitrous oxide or opioids).
The concurrent administration of potent inhalational agents (e.g.,
isoflurane, enflurane, and halothane) during maintenance with
PROPOFOL Injectable Emulsion has not been extensively
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evaluated. These inhalational agents can also be expected to
increase the anesthetic or sedative and cardiorespiratory effects
of PROPOFOL Injectable Emulsion.
PROPOFOL Injectable Emulsion does not cause a clinically
significant change in onset, intensity or duration of action of the
commonly used neuromuscular blocking agents (e.g.,
succinylcholine and nondepolarizing muscle relaxants).
No significant adverse interactions with commonly used
premedications or drugs used during anesthesia or sedation
(including a range of muscle relaxants, inhalational agents,
analgesic agents, and local anesthetic agents) have been observed
in adults. In pediatric patients, administration of fentanyl
concomitantly with PROPOFOL Injectable Emulsion may result
in serious bradycardia.

Dosage and Administration

Propofol blood concentrations at steady-state are generally
proportional to infusion rates, especially in individual patients.
Undesirable effects such as cardiorespiratory depression are
likely to occur at higher blood concentrations which result from
bolus dosing or rapid increases in the infusion rate. An adequate
interval (3 to 5 minutes) must be allowed between dose
adjustments to allow for and assess the clinical effects.
Shake well before use. Do not use if there is evidence of excessive
creaming or aggregation, if large droplets are visible, or if there
are other forms of phase separation indicating that the stability of
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the product has been compromised. Slight creaming, which
should disappear after shaking, may be visible upon prolonged
standing.
When administering PROPOFOL Injectable Emulsion by
infusion, syringe or volumetric pumps are recommended to
provide controlled infusion rates. When infusing PROPOFOL
Injectable Emulsion to patients undergoing magnetic resonance
imaging, metered control devices may be utilized if mechanical
pumps are impractical.

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Product in the Market

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