PROPOFOL

Propofol is an intravenous anesthetic agent widely used in modern anesthesia practice. It has gained importance in recent years due to its favorable properties and advantages over other anesthetic agents. Some key reasons for the importance of propofol anesthesia are:

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1. Rapid onset and recovery: Propofol has a rapid onset of action, usually taking effect within 30 seconds to a minute. It also has a short duration of action, which allows patients to recover quickly after the procedure. This makes it ideal for short procedures, outpatient surgeries, and reducing time spent in the recovery room.

2. Smooth induction and emergence: Propofol provides a smooth and pleasant induction, and patients usually experience a calm and comfortable awakening. This reduces the incidence of post-operative agitation, delirium, and other negative side effects that can occur with other anesthetics.

3. Antiemetic properties: Propofol has been shown to reduce the incidence of postoperative nausea and vomiting (PONV). This is an important advantage, as PONV is a common and distressing side effect of anesthesia and surgery.

4. Neuroprotective effects: Propofol has been shown to have potential neuroprotective effects in certain situations, such as during neurosurgical procedures or in patients with traumatic brain injury. It can help reduce brain damage by decreasing the metabolic rate of the brain and reducing the production of harmful molecules.

5. Antioxidant properties: Propofol has antioxidant properties, which may contribute to its neuroprotective effects and reduce the impact of oxidative stress on the body during surgery.

6. Use in ICU sedation: Propofol is commonly used for sedation in the intensive care unit (ICU) due to its rapid onset and short duration of action. It allows for quick adjustments in sedation levels and easy titration, which is important in critically ill patients.

7. Bronchodilatory effects: Propofol can help relax the airway muscles and has bronchodilatory effects, making it a good choice for patients with asthma or other airway-related issues.

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Here are the main steps in propofol's mechanism of action:

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1. Binding to GABA-A receptors: Propofol acts by binding to a specific allosteric site on the GABA-A receptor complex, which is a ligand-gated ion channel composed of several protein subunits. This binding site is distinct from the site where the endogenous ligand GABA binds.

2. Modulation of GABA-A receptors: When propofol binds to the GABA-A receptor, it enhances the receptor's affinity for GABA, making it more responsive to the neurotransmitter. This leads to an increased frequency of the opening of the chloride ion channels associated with the GABA-A receptor complex.

3. Increase in chloride ion conductance: The enhanced responsiveness of the GABA-A receptors to GABA results in an increased influx of chloride ions into the neuron. This causes hyperpolarization of the neuronal membrane, making it more difficult for the neuron to generate action potentials and transmit signals.

4. Inhibition of neuronal activity: The overall effect of propofol's action on the GABA-A receptors is the suppression of neuronal excitability within the central nervous system. This leads to the rapid onset of unconsciousness and general anesthesia.

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                                                                                                  Key points about Propofol

• Propofol is a 2, 6-diisopropyl phenol.

• Propofol is prepared in the form of a lipid emulsion (soybean oil, glycerol, and egg lecithin).

• Propofol formulations can support the growth of bacteria. Careful handling and aseptic conditions are recommended.

• Propofol should be administered within 6 h of opening the ampule.

• Propofol’s clearance exceeds hepatic blood flow (extrahepatic metabolism).

• Decreased plasma protein levels may lower drug binding and increase the free active fraction.

• Propofol decreases cerebral blood flow (CBF), cerebral metabolic rate of oxygen consumption (CMRO2), intracranial pressure (ICP), and cerebral perfusion pressure (CPP).

• Propofol has anticonvulsant properties.

• Propofol decreases intraocular pressure.

• Cerebral autoregulation is  preserved with propofol.

• Propofol decreases systemic vascular resistance (SVR), preload and cardiac contractility.

• Propofol markedly impairs the normal arterial baroreflex response to hypotension.

• Propofol does not inhibit hypoxic pulmonary vasoconstriction (HPV).

• Propofol can cause disinhibition of subcortical centers resulting in spontaneous excitatory movements secondary and myoclonus.

• Propofol possesses antiemetic effects.

• Propofol exhibits antipruritic effects against opioid-induced pruritus.

• Propofol easily passes the placental barrier.

• Lecithin is from egg yolks. Patients with egg allergies demonstrate hypersensitivity to proteins from egg whites.

• Propofol is a free radical scavenger.

• Propofol infusion syndrome: cardiomyopathy, rhabdomyolysis, metabolic acidosis, hyperkalemia, hepatomegaly, lipemia, renal failure.

• Smaller induction dose is recommended in older adult patients because of their smaller  volume of distribution (Vd).

• Propofol is conjugated in the liver resulting in inactive metabolites that are eliminated by renal clearance.

• The pharmacokinetics of propofol are not affected by cirrhosis or kidney failure.