Propofol: A Sedative-Hypnotic Anesthetic Agent for Use in Ambulatory Procedures: PHARMACODYNAMICS

In: Anesthesia

13 Jan 2010

The most clinically significant pharmacodynamic properties of propofol deal with the neurologic, cardiovascular, and respiratory systems. Propofol produces rapid hypnosis and has synergistic activity when administered concurrently with barbiturates, benzodiazepines, and opioids. Hypnosis is induced by the action of propofol on the alpha subunit of the 7-aminobutyric acid (GABA) receptor in the brain. Anticonvulsant activity is exhibited by propofol and is also likely mediated by central GABA receptors. A decrease in cerebral bloodflow by up to 50%, with a simultaneous decrease in intracranial pressure, is seen following propofol delivery. This absolute reduction in cerebral vascular perfusion is particularly pronounced in the medial thalamus, the cuneus and precuneus, the posterior cingulate and orbitofrontal gyri, and the right angular gyrus. These regions are responsible for the control of the consciousness, associative functions (especially those related to visual inputs), and autonomic control. The fact that some neuronal circuits are more sensitive than others to the drug suggests that specific effects on neuronal activity, not a nonspecific regional effect on the central nervous system vasculature, are induced by propofol. Also, a decrease by 18-36% of cerebral metabolic oxygen requirements is observed, but cerebral autoregulation is maintained during propofol infusion.

Hypotension, resulting primarily from the reduction in systemic vascular resistance, is the major cardiovascular effect of propofol. The drug may also induce negative inotropy, a depression of myocardial contractility leading to a reduced cardiac output. Also, bradycardia is occasionally observed, possibly due to drug action on the conduction system or autonomic nervous system. The reduction in systemic vascular resistance and heart rate help in the control of stress responses. Hypovolemia and opioid use potentiate the hypotensive effects of propofol. In general, propofol is associated with adequate hemodynamic stability in patients requiring sedation in a variety of settings, including those recovering from coronary bypass graft surgery. erectalis 20 mg

Effects on the respiratory system include a dose-dependent reduction in minute ventilation, tidal volume, and functional residual capacity. Because of propofol’s respiratory depressant qualities, the drug should be used with caution when administered with opioids, as apnea will occur in many patients when these drugs are administered together. Also, intubation can be facilitated because propofol depresses pharyngeal reflexes and decreases masticatory tonus, which may obviate the need for paralyzing agents during routine intubations.

Liver and adrenal functions are not adversely affected by propofol. The drug is metabolized in the liver by the cytochrome p450 system and is eliminated from the body in the urine. Only minimal amounts of propofol are excreted in the feces. There are reduced incidences of postoperative nausea and vomiting compared with other intravenous anesthetic drugs. Propofol has no effect on adrenal steroidogenesis and is not immunosuppressive.

FORMULATION AND ADMINISTRATION

Propofol is a sedative-hypnotic IV anesthetic drug. The rapid onset and recovery make it an ideal agent for use in ambulatory procedures like oral and maxillofacial surgery. It has very little analgesic properties and is safe and efficacious in all phases of general anesthesia. Because of the few side effects and smooth recovery characteristics, propofol has proven to be quite useful in pediatric, geriatric, and mentally and/or physically handicapped patients. The drug is available in 20-mL and 50-mL vials, and the lipophilic nature of propofol necessitates an oil-in-water emulsion consisting of 1.0% propofol, 10% soybean oil, 2.25% glycerol, and 1.2% egg phosphatide. Although originally thought to be contraindicated in patients who are allergic to eggs, that theoretical consideration is no longer judged to be a concern.

Propofol has been found efficacious for three different clinical applications: (1) IV bolus for anesthesia induction, (2) IV infusion or repeated bolus for maintenance of anesthesia, and (3) IV bolus or repeated bolus for sedation. canadian pharmacy cialis


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