Flashcards in Propofol Deck (36):
What are the trade names for Propofol?
Ampofol or Diprivan
What is the formal drug classification of Propofol?
Substituted isopropylphenol (2,6-diisopropylphenol)
What are the clinical uses for Propofol? (8)
-Induction and maintenance of GA
-Same day surgery due to a fast onset and fast recovery and absence of "hangover effect"
-Useful for decreasing ICP and IOP
-Attenuation of bronchoconstriction
What is the MOA of Propofol?
Exerts sedative-hypnotic effects by discouraging dissociating of the Neurotransmitter GABA from the GABAa receptor, thus increasing transmembrane chloride conductance resulting in hyperpolarization of the POSTsynaptic cell membrane and functional inhibition of the postsynaptic neuron
-Effect is modulation of GABA at the GABAa receptor--specificallythe Beta subunits 1-3
-Dr. E says also NMDA inhibition
What is a secondary MOA of Propofol?
a secondary MOA of propofol is via inhibition of glutamate action at NMDA receptors
What receptor does propfol exert its effects? pre or post synaptically?
GABAa; postsynaptically! functional inhibition of the postsynaptic neuron
What is the onset of action of Propofol?
Fast onset within 20 - 30 seconds
What is the Elimination 1/2 life of Propofol?
4 - 7 hours or 0.5 - 1.5 hours(Dr. E says 0.5-1.5hrs)? depending on the text......
context sensitive 1/2 time for infusions up to 8 hrs is <40 minutes
How is propofol metabolized?
-Rapidly metabolized in the liver by conjugation to glucuronide and sulfate by CPY450 to produce water-soluble compounds which are excreted by the kidneys
-because clearance exceeds hepatic blood flow (1.5-2.2 L/min), extrahepatic metabolism or extra renal elimination is suggested
-lungs play a role in extrahepatic metabolism and are responsible for uptake and first pass elimination
How is Propofol redistributed?
-Initial distribution 2-8 minutes
- whole blood propofol levels decrease rapidly after a single bolus injection
What is the elimination route of propofol?
Less than 0.3% of a dose is excreted unchanged in the urine
What is the volume of distribution of Propofol?
3.5 - 4.5 L/kg
What are the side effects of Propofol? (4)
-Pain on injection, MYOCLONUS, Apnea, Hypotension, Propofol infusion syndrome
-Severe Bradycardia and asystole, risk of infection, Hypertriglyceridemia with prolonged administration, PE, Allergic rxns, Seizures, lactic acidosis, proconvulsant activity, antioxidant properties, abuse potential: amorous behavior, intense dreams, and hallucinations during recovery
-CV and Resp depression
-Dose-dependent reduction of CBF and CMRO2, capable of producing an isoelectric EEG and decreases CPP dependent on decreases in BP
What are the symptoms of propofol infusion syndrome?
-Poor oxygen delivery
-Serious cerebral injury
What are contraindications to the use of Propofol?
-Patients that have multiple drug allergies should use with caution; allergies to EGG or SOYBEAN oil
-use extreme caution in patients with poor myocardial function and in patients with predicted difficult airways before artificial a/w established
What are the drug interactions with Propofol?
-When combined with propofol the required infusion rate and concentration of opioids, midazolam, clonidine, or ketamine is reduced
-Opioids alter the concentration required for adequate anesthesia, the relative dose of either opioid or propofol markedly affects the time from termination of drug to awakening and recovery
-the pressor response to ephedrine is altered by propofol and the effect of atropine in increasing HR is also attenuated
-mixing with any other drug is not recommended although lidocaine has been frequently added in attempt to prevent pain with IV injection
What is the induction of GA dose for Propofol?
1 - 2.5 mg/kg IV (as high as 3 mg/kg in toddlers due to pharmacokinetic differences)
When should the IV induction of GA dose of Propofol be reduced?
with increasing age and/or myocardial dysfunction
What is the maintenance of GA dosage of Propofol?
100 - 300 mcg/kg/min IV
What is the sedative dosage of GA for Propofol?
25 - 100 mcg/kg/min IV
What is the antiemetic dose for Propofol?
10 - 20 mg IV, can repeat every 5-10 minutes, or start infusion of 10 mcg/kg/min
How is propofol prepared in solution?
Propofol is in a 1% aqueous solution of 10% soybean oil, 2.25% glycerol, and 1.2% purified egg phosphatide
Does Propofol trigger malignant hyperthermia?
What is a precaution with propofol and bacteria?
This long-chain triglyceride formulation supports bacterial growth!
What is Propofol at room temperature?
OIL, insoluble in aqueous solution->VERY lipid soluble
How is Propofol supplied?
Supplied as: 1% solution in egg, soy, glycerol base
-egg yolk allergies (that is where the egg lecithin comes from)
How is infection controlled with Propofl?
EDTA (disodium edetate)
What are the preservatives in Propofol? what is important to note about one of them?
-Sodium Metabisulfite vs EDTA
-Sodium Metabisulfite can cause bronchospasms!!
Does Propofol have active metabolites?
NO; metabolites are inactive
What are the CNS effects of Propofol?
-Rapid onset, one arm-brain circulation
-Decreases CBF, ICP, IOP, CMRO2 and CPP, CEREBROPROTECTIVE
-EEG burst suppression and decrease in BIS value
-Age affects ED95 (highest in toddlers and decreases with age; so MUST reduce dose in elderly)
-Hiccoughing, muscle twitching
-Antioxidant effects resemble Vitamin E-> cerebroprotection
What are the respiratory effects of Propofol?
-Apnea following induction dose
-Decreases Vt, RR effect variable
-Decreases ventilatory response to CO2 and hypoxia
-PaCO2 rises, pH decreases
-Bronchodilation in COPD patients
-HPV (hypoxic pulmonary vasoconstriction) remains intact
What are the CV effects of Propofol?
-25-40% decrease in arterial BP
-decrease in BP is greater than in TPL
-Dose dependent MYOCARDIAL DEPRESSION and VASODILATION result in
-similar decreases in SV, CO, and SVR
-HR unchanged (? baroreceptor inhibition?)
Does Propofol have an effect on muscle relaxants?
does NOT potentiate muscle relaxants
In subhypnotic doses of Propofol (10mg) what effects are produced?
Antiemetic and antipruritic
What doses produce Amnesia?