PROPOFOL

INTRODUCTION

2,6 DISIOPROPYL PHENOL

HIGHLY LIPID SOLUBLE
1 % PREPARATION
ISOTONIC EMULSION
10 % SOYA OIL (LONG CHAIN TRIGLYCERIDES)
NA HYDROXIDE
PURIFIED EGG PHOSPHATIDE AND WATER
INTRODUCTION
• 2% PREPARATION IS COMMONLY USED IN THE
CONTINOUS INFUSION TECHNIQUES
• BOTH THE PREPARATIONS HAS A RISK OF
BACTERIAL GROWTH
• OUTBREAK OF P/O INFECTON HAS BEEN
REPORTED RELATED TO USE OF PROPOFOL IN
UNSTERILE CONDITIONS AND TO THE REPEATED
USE OF SINGLE DOSE AMPOULES ...SO
SYRINGES CONTAINING PROPOFOL SHOULD BE
USED IMMEDIATELY AFTER THEIR PREPARATION
UNUSED DRUG SHOULD BE DISCARDED
INTRODUCTION

PREVIOUSLY OPENED AMPOULES OF THE DRUG

SHOULD NOT BE ALLOWED TO STAND AT AMBIENT
TEMPRATURE
MODE OF ACTION

• IT ACTS ON GABAA RECEPTOR

• AMINO ACID RESIDUE BETA 2 AND 3 SUB UNITS
• PROPOFOL ALSO ACTS ON GLYCINE RECEPTORS
AND NICTONIC RECEPTORS AND ALSO INHIBITS
EXCITATORY NICTONIC ACH RECEPTORS
DISTRIBUTION

IV ADMINISTRATION OF PROPOFOL HAS RAPID AND

WIDE DISTRIBUTION BECAUSE OF ITS HIGH LIPID
SOLUBILITY
VOLUME OF DISTRIUTION IS 20 TO 80 TIMES
GREATER THAN TOTAL BODY WATER
AS THE PLASMA CONCENTRATION FALLS DUE TO
EXTENSIVE TISSUE UPTAKE AND RAPID HEPATIC
METABOLISM PROPOFOL IS RAPIDLY REMOVED
FROM BRAIN DOSE DEPENDENT RECOVERY
OCCURS IN 10 TO 20 MINUTES
DISTRIBUTION

• HIGHLY BOUND TO ALBUMIN (96 TO 97%)

• PLASMA CONCENTRATION INCREASES THAN THE
LEVEL OF UNBOUND FRUG
METABOLISM

• PROPOFOL IS REDUCED INTO 2,6 DISIOPROPYL

QUINOL AND SUBSEQUENTLY ELIMINATED IN
URINE AS A GLUCRONIDE SULPHATE
CONJUGATES BY CYP2B6 AND CYPP2C9
• GREEN COLORED URINE AFTER PROLONGED
INFUSIONS BECAUSE OF ITS QUINOLIC
METABOLISM
• ELIMINATION IS SENSITIVE TO CHANGES IN LIVER
BLOOD FLOW
• UNALTERD IN PROTEIN BINDING AND ENZYME
ACTIVITY
METABOLISM
CLEARANCE > LIVER BLOOD FLOW
EXTRAHEPATIC METABOLISM ALSO OCCURS IN LUNGS
, ENTERIC CIRCULATION ...HAS ABILITY TO FORM
GLUCRONIDE CONJUGATE
IT INHIBITS CYP450 ,CYP1A1,CYP2A1,CYP2B1 AND
DECREASE THE CLEARNACE OR MAY PROLONG THE
DURATION OF FENTANYL , ALFENTANIL ,
PROPRANOLOL AND INHIBITS DRUG METABOLISM
PROPOFOL DOES NOT INDUCE ENZYMES INVOLVED IN
PORPHYRIN SYNTHESIS AND NOT C/I IN THE DISEASE
PHARMACOKINETICS
PHARMACOKINETICS

• Elimination half life 4 to 7 hrs

• Clearance 20 to 30 ml/kg/min
• Volume of distribution 2 to 10 l/kg
• Context sensitive half life is 40 min for 8 hours infusion
PHARMACOKINETICS
IV BOLUS 1TO4 MG/KG , DECREASE IN THE PLASMA
CONCENTRATION WITH TRIEXPONENTIAL DECLINE
RAPID DURING FIRST 10 MINUTES HALF LIFE 1 TO 3
MINUTES FOLLOWED BY SLOWER DECLINE HALF LIFE
IS 20 TO 30 MINUTES IS DUE TO THE IMMEDIATE
DISTRIBUTION AND UPTAKE BY TISSUES
SLOWER DECLINE IS DUE TO THE HEPATIC
METABOISM
TERMINAL HALF LIFE IS 1 TO 5 HRS
CLEARANCE 20 % >LIVER BLOOD FLOW IS DUE TO THE
EXTRAHEPATIC METABOLISM
EFFECTS ON CNS

• INDUCTION DOSE OF PROPOFOL 1.5 TO 2.5

MG/KG
• PRODUCES RAPID LOSS OF CONSCIOUSNESS
BECAUSE OF ITS HIGH LIPID SOLUBILITY
• LOSS OF VERBAL CONTACT IS THE PRECISE
ENDPOINT FOR LOSS OF CONSCIOUSNESS
EFFECTS ON CNS

EEG
INDUCTON : EEG FREQUENCY DECREASES AND
AMPLTUDE INCREASES
AS THE LEVEL OF GENERAL ANAESTHESIA
DEEPENS BETA AND DELTA WAVES PREDOMINATE
EFFECTS ON CNS
• IT DECREASES THE CEREBERAL BLOOD FLOW
• IT DECREASES CEREBERAL OXYGEN
CONSUMPTON
• IT DECREASES INTRACRANIAL PRESSURE AND
CEREBRAL PERFUSION PRESSURE
• WHEN THE PLSAMA CONCENTRATION DROPS
PROPOFOL DIFFUSES FROM CNS TO SYSTEMIC
CIRCULATION
• RAPID RECOVERY OF FULL CONSCIOUDNESS
AND AWARENESS DUE TO RAPID
REDISTRIBUTION OF THE DRUG
RESPIRATORY SYSTEM

IT CAUSES DOSE RELTED RESPIRATORY

DEPRESSION
IT DECREASES THE TIDAL VOLUME AND MINUTE
VENTILATION
APNOEA MAY BE OBSERVED
CVS

• IT DECREAES THE SYSTOLIC BLOOD PRESSURE

70 TO 80 % OF THE PREOPERATIVE LEVEL
• RELATED TO DOSE AND RATE OF INJECTION AND
USUALLY MAXIMUM WITHIN 5 TO 10 MINUTES
• PROPOFOL DECREASES SYSTEMIC VASCULAR
RESISTANCE AND NOT USUALLY ACCOMPANIED
BY REFLEX TACHYCARDIA
CVS

• RESETS THE BARORECEPTORS IN THE AORTIC

ARCH AND CAROTID BODY
• CALCIUM CHANNEL BLOCKING AGENT
• RELEASE OF NITROUS OXIDE FROM
ENDOTHELIUM
• PROPOFOL DECREASES THE CARDIAC OUTPUT
USES

INDUCTION
MAINTENENCE
SUPPLEMENT ANAESTHESIA DURING DIAGNOSTIC
PROCEDURES AND TO PROVIDE SEDATION IN
ADULTS DURING ICU CARE
TARGETED CONTROLLED INFUSION SYSTEM
ANTIPRURITIC,ANTIEMETIC,ANTICONVULSANT
ACTIVITY
USES

INDUCTION (1.5 TO 2.5 MG/KG)

RATE OF 20 TO 40 MG / 10 SECONDS
SINCE IT ABOLISHES THE REFLEXES INDUCED BY
INTUBATION IT IS WIDELY USED TO INDUCE
GENERAL ANAESTHESIA DOSE DECREASES IN
PATIENTS AGED MORE THAN 55 YEARS
IN ICU SITUATIONS DOSE IS 0.5 TO 1 MG /KG TO
INDUCE AND FOLL BY INFUSION OF 0,5 TO 4 MG/KG
ADVANTAGES

RAPID RECOVERY OF CONSCIOUSNESS AND FULL

AEARNESS WHEN BOLUS DOSES USED TO INDUCE
ANAESTHESIA
DAY CARE ANAESTHESIA
RESPIRATORY SIDE EFFECTS ARE RARELY
ENCOUNTERED
DOC -LMA INSERTION
TARGET CONTROLLED INFUSION SYSTEMS
The procedure is based on the use of the bolus, elimination and
transfer method and appropriate compartmental pharmacokinetic
model . A bolus of drug sufficient to fill the central compartment to
the required concentration is administered, followed by a continuous
infusion at an exponentially declining rate to compensate for the
disappearance of the drug from the central compartment and its
transfer to one or more peripheral compartments
SIDE EFFECTS

PAIN ON INJECTION
EXCITATORY EFFECTS
BRADYCARDIA AND HYPOTENSION
ALLERGIC REACTIONS
PAIN ON INJECTION

• SAMLL VEINS ON THE DORSUM OF HAND OR

WRIST
• PROXIMAL SITE UPPER ARM AND SHOULDER
• PAIN CAN BE REDUCED BY CHOOSING LARGE
VEINS IN THE ANTECUBITAL FOSSA
• ADDITION OF LIGNOCAINE 10 TO 20 MG BEFORE
OR ADDED TO PROPOFOL DECREASES THE PAIN
• FENTANYL ,ALFENTANIL,TRAMADOL CAN ALSO
BE ADDED
EXCITATORY EFFECTS

MYOCLONUS,OPISTHOTONOS,CONVULSIONS MAY
OCCUR WHILE ADMINISTRATION OR DURING
RECOVERY PERIOD
RISK OF CONVULSIONS IN EPILEPTIC PATIENTS AND
ONSET IS SOMETIMES DELAYED
BRADYCARDIA AND
HYPOTENSION
HR DECREASES AND MAY REQUIRED
ANTIMUSCRANIC AGENT (LIKE ATROPINE)
UNEXPECTED DEATHS IN CHILDERN HAD OCCURED
IN LONG TERM SEDATION WITH PROPOFOL IN A
INTENSIVE CARE UNIT
METABILIC ACIDOSIS , BRADYCARDIA AND
PROGRESSIVE MYOCARDIAL FAILURE MAY OCCUR
AND THE CAUSE IS OBSCURE
ALLERGIC REACTIONS

ACREMAPHOR EL RESULTED IN HYPERSENSTIVITY

REACTIONS
SOYA OIL ASSOCIATED WITH LESS THAN 30 %
ANAPHAYLACTOID REACTIONS
SAFETY MARGIN
ETOMIDATE>PROPOFOL>THIOPENTONE
PROPOFOL INFUSION
SYNDROME
• Propofol infusion syndrome is a rare but lethal syndrome
associated with infusion of propofol at 4 mg/kg/hr or
more for 48 hours or longer.
• It was first described in children, but subsequently has
been observed in critically ill adults.
• The clinical features of propofol infusion syndrome are
acute refractory bradycardia leading to asystole, in the
presence of one or more of the following: metabolic
acidosis (base deficit >10 mmol/L−1), rhabdomyolysis,
hyperlipidemia, and enlarged or fatty liver.
PROPOFOL INFUSION
SYNDROME
• Other features include cardiomyopathy with acute
cardiac failure, skeletal myopathy, hyperkalemia,
hepatomegaly, and lipemia.
• causality include mitochondrial toxicity, mitochondrial
defects, impaired tissue oxygenation, and
carbohydrate deficiency. The major risk factors for
its development seem to be poor oxygen delivery,
sepsis, serious cerebral injury, and high propofol
dosage
CONTRAINDICATIONS

• HYPERSENSITIVITY TO PROPOFOL INJECTABLE EMULSIONS

OR ANY OF ITS COMOPONENTS
• ALLERGIES TO EGGS,EGGS PRODUCTS ,SOYBEANS OR SOY
PRODUCTS