Propofol

Question 1

What are the trade names for Propofol?

Answer 1

Ampofol or Diprivan

Question 2

What is the formal drug classification of Propofol?

Answer 2

Substituted isopropylphenol (2,6-diisopropylphenol)

General Anesthetic

Question 3

What are the clinical uses for Propofol? (8)

Answer 3

• Induction and maintenance of GA
• IV sedation
• Same day surgery due to a fast onset and fast recovery and absence of “hangover effect”
• Anticonvulsant activity
• Useful for decreasing ICP and IOP
• Antiemetic
• Antipruritic
• Attenuation of bronchoconstriction

Question 4

What is the MOA of Propofol?

Answer 4

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

Question 5

What is a secondary MOA of Propofol?

Answer 5

a secondary MOA of propofol is via inhibition of glutamate action at NMDA receptors

Question 6

What receptor does propfol exert its effects? pre or post synaptically?

Answer 6

GABAa; postsynaptically! functional inhibition of the postsynaptic neuron

Question 7

What is the onset of action of Propofol?

Answer 7

Fast onset within 20 - 30 seconds

Question 8

What is the Elimination 1/2 life of Propofol?

Answer 8

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

Question 9

How is propofol metabolized?

Answer 9

• 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

Question 10

How is Propofol redistributed?

Answer 10

• Initial distribution 2-8 minutes

- whole blood propofol levels decrease rapidly after a single bolus injection

Question 11

What is the elimination route of propofol?

Answer 11

Less than 0.3% of a dose is excreted unchanged in the urine

Question 12

What is the volume of distribution of Propofol?

Answer 12

3.5 - 4.5 L/kg

Question 13

What are the side effects of Propofol? (4)

Answer 13

• 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

Question 14

What are the symptoms of propofol infusion syndrome?

Answer 14

• Poor oxygen delivery
• Sepsis
• Serious cerebral injury
• Lipemia

Question 15

What are contraindications to the use of Propofol?

Answer 15

• 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

Question 16

What are the drug interactions with Propofol?

Answer 16

• 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

Question 17

What is the induction of GA dose for Propofol?

Answer 17

1 - 2.5 mg/kg IV (as high as 3 mg/kg in toddlers due to pharmacokinetic differences)

Question 18

When should the IV induction of GA dose of Propofol be reduced?

Answer 18

with increasing age and/or myocardial dysfunction

Question 19

What is the maintenance of GA dosage of Propofol?

Answer 19

100 - 300 mcg/kg/min IV

Question 20

What is the sedative dosage of GA for Propofol?

Answer 20

25 - 100 mcg/kg/min IV

Question 21

What is the antiemetic dose for Propofol?

Answer 21

10 - 20 mg IV, can repeat every 5-10 minutes, or start infusion of 10 mcg/kg/min

Question 22

How is propofol prepared in solution?

Answer 22

Propofol is in a 1% aqueous solution of 10% soybean oil, 2.25% glycerol, and 1.2% purified egg phosphatide

Question 23

Does Propofol trigger malignant hyperthermia?

Answer 23

NO

Question 24

What is a precaution with propofol and bacteria?

Answer 24

This long-chain triglyceride formulation supports bacterial growth!

Question 25

What is Propofol at room temperature?

Answer 25

OIL, insoluble in aqueous solution->VERY lipid soluble

Question 26

How is Propofol supplied?

Answer 26

Supplied as: 1% solution in egg, soy, glycerol base | -egg yolk allergies (that is where the egg lecithin comes from)

Question 27

How is infection controlled with Propofl?

Answer 27

EDTA (disodium edetate)

Question 28

What are the preservatives in Propofol? what is important to note about one of them?

Answer 28

- Sodium Metabisulfite vs EDTA | - Sodium Metabisulfite can cause bronchospasms!!

Question 29

Does Propofol have active metabolites?

Answer 29

NO; metabolites are inactive

Question 30

What are the CNS effects of Propofol?

Answer 30

- 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 - Hallucinations, opisthothonos - Antioxidant effects resemble Vitamin E-> cerebroprotection

Question 31

What are the respiratory effects of Propofol?

Answer 31

- 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

Question 32

What are the CV effects of Propofol?

Answer 32

- 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?)

Question 33

Does Propofol have an effect on muscle relaxants?

Answer 33

does NOT potentiate muscle relaxants

Question 34

In subhypnotic doses of Propofol (10mg) what effects are produced?

Answer 34

Antiemetic and antipruritic

Question 35

What doses produce Amnesia?

Answer 35

>30 mcg/kg/min

Question 36

Can propofol cross the placenta?

Answer 36

crosses placenta, rapidly removed from fetal circulation