Anesthetic propofol

A report on the binding of the anesthetic propofol to human serum albumin and to plasma presents a dataset that challenges simple notions of equilibria [70]. The unbound fraction of propofol was found to increase sharply at low drug concentrations. The authors appear to have carefully eliminated possible artifacts. Explanations based on cooperative binding modes are discussed though no clear explanation emerges. 

TIVA has become feasible thanks to the introduction of agents with a suitably short duration of action, including the injectable anesthetics propofol and etomidate, the analgesics alfentanil und remifentanil, and the muscle relaxant mivacurium. These drugs are eliminated within minutes after being adminster-ed, irrespective of the duration of anesthesia. 

Bhattacharya AA, Curry S, Franks NP (2000) Binding of the general anesthetics propofol and halothane to human... 

Drugs with a high lipid content, when given concurrently with lipid-containing parenteral nutrition, can aggravate the problems of lipid overload (29). The anesthetic, propofol, which is used for continuous sedation in a dose of 1-3 mg/kg/hour (an equivalent of 300-500 ml of a 10% fat emulsion), may aggravate the symptoms and pathological effects of fat overload (29). 

Figure 2 Chemical structures for (a) inhalational anesthetics and (b) the intravenous anesthetic propofol.

Other general anesthetics (propofol) Negative inotropic effect Ca + channel blockade Altered Ca " homeostasis, /i-adrenergic receptor sensitization... 

Patel S, Wohlfeil ER, Rademacher DJ, Carrier EJ, Perry LJ, Kundu A, Falck JR, Nithipatikom K, Campbell WB, Hillard CJ (2003) The general anesthetic propofol increases brain... 

Bai D. The general anesthetic propofol slows deactivation and desensitization of GABAa receptors. J Neurosci 1999 19 10635-10646. 

Patel, S., Wohlfeil, E.R., Rademacher, D.J., Carrier, E.J., Perry, L.J., Kundu, A., Falck, J.R., Nithipatikom, K., Campbell, W.B., and Hillard, C.J. (2003) The general anesthetic propofol increases brain N-arachi-donylethanolamine (anandamide) content and inhibits fatty acid amide hydrolase. Br J Pharmacol. 139 1005-1013. 

Figure 11 Structures of the intravenous anesthetic propofol 13 and the carbonate ester template of propofol 14 (Ref. 17).

The intravenous anesthetic propofol is synthesized in four steps from phenol (See Example 10.9)... 

D-Glucuronic acid is widely distributed in both the plant and animal worlds. In humans, it is an important component of the acidic polysaccharides of connective tissues. The body also uses it to detoxify foreign phenols and alcohols. In the liver, these compounds are converted to glycosides of glucuronic acid (glucuronides), to be excreted in the urine. The intravenous anesthetic propofol (Problem 10.43), for example, is converted to the following water-soluble glucuronide and then excreted in the urine ... 

Bennett SN, McNeil MM, Bland LA, Arduino MJ, Villarino ME, Perrotta DM, Burwen DR, Welbel SF, Pegues DA, Stroud L, Zeitz PS, Jarvis WR. Postoperative infections traced to contamination of an intravenous anesthetic, propofol. N Engl J Med 1995 333(3) 147-54. 

Another clue about awareness comes from studies of brain activity with the anesthetic propofol. When this chemical saturates the brain and knocks you unconscious, all brain areas participate in a synchronized undulation. At the moment when awareness is lost, a low-frequency wave of firing neurons sweeps across the brain. Most brain areas continue to connect within their own area, but the connections between separate areas are lost. As consciousness fragments, so does the connectivity of the brain. 

Leon I, Cocinero EJ, Millan J, Jaeqx S, Rijs AM, Lesarri A, Castano F, Fernandez JA (2012) Exploring microsolvation of the anesthetic propofol. Phys Chem Chem Phys 14 (13) 4398 409... 

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