Anesthetics elimination

The narcotic potency and solubiUty in oHve oil of several metabohcaHy inert gases are Hsted in Table 10. The narcotic potency, ED q, is expressed as the partial pressure of the gas in breathing mixtures requited to produce a certain degree of anesthesia in 50% of the test animals. The solubiUties are expressed as Bunsen coefficients, the volume of atmospheric pressure gas dissolved by an equal volume of Hquid. The Hpid solubiHty of xenon is about the same as that of nitrous oxide, a commonly used light anesthetic, and its narcotic potency is also about the same. As an anesthetic, xenon has the virtues of reasonable potency, nonflammability, chemical inertness, and easy elimination by the body, but its scarcity and great cost preclude its wide use for this purpose (see Anesthetics). 

Prilocaine hydrochloride [1786-81-8] is also similar in profile to Hdocaine, although prilocaine has significantly less vasodilator activity. Prilocaine is the least toxic of the amino amide local anesthetics. However, its tendency to cause methemoglobinemia, especially in newborns, has eliminated its use in obstetric surgery. 

The toxic effect depends both on lipid and blood solubility. I his will be illustrated with an example of anesthetic gases. The solubility of dinitrous oxide (N2O) in blood is very small therefore, it very quickly saturates in the blood, and its effect on the central nervous system is quick, but because N,0 is not highly lipid soluble, it does not cause deep anesthesia. Halothane and diethyl ether, in contrast, are very lipid soluble, and their solubility in the blood is also high. Thus, their saturation in the blood takes place slowly. For the same reason, the increase of tissue concentration is a slow process. On the other hand, the depression of the central nervous system may become deep, and may even cause death. During the elimination phase, the same processes occur in reverse order. N2O is rapidly eliminated whereas the elimination of halothane and diethyl ether is slow. In addition, only a small part of halothane and diethyl ether are eliminated via the lungs. They require first biotransformation and then elimination of the metabolites through the kidneys into the... 

The low structural specificity in the local anesthetic sell cs is perhaps best illustrated by phenacalne (91), a local an-I -.lhetic that lacks not only the traditional ester or amide func-I ion but the basic aliphatic nitrogen as well. First prepared at I lie turn of the century, a more recent synthesis starts by con-ili iusation of p-ethoxyaniline with ethyl orthoacetate to afford I he imino ether (90), Reaction of that intermediate with a sec-I liil mole of the aniline results in a net displacement of ethanol, iiobably by an addition-elimination scheme. There is thus ob-I.lined the amidine, 91, phenacalne. 

Jakobson I, Wahlberg JE, Holmberg B, et al. 1982. Uptake via the blood and elimination of 10 organic solvents following epicutaneous exposure of anesthetized guinea pigs. Toxicol Appl Pharmacol 63 181-187. 

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. 

Fish rapidly eliminate residues of MS-222 after exposure to the anesthetic (27). Blood, kidney, liver, and muscle show different rates of elimination, which probably reflect the form of the drug present and fluid turnover times in the tissues. The concentration of the anesthetic in these tissues decreased to the detection limit of their method within 5 h. 

Gases that do not react irreversibly with epithelial tissue, such as anesthetic gases, may diffuse into the bloodstream and will ultimately be eliminated from the body. A different and earlier model developed by DuBois and Rogers estimates the rate of uptake of inhaled gas from the tracheobronchial tree in terms of diffusion through the epithelial tissue, rate of blood flow, and solubility of the gas in blood. The rate of uptake from the airway lumen is determined by the equation ... 

In regional anesthesia (spinal anesthesia) with a local anesthetic (p. 204), nociception is eliminated, while consciousness is preserved. This procedure, therefore, does not fall under the definition of general anesthesia... 

Inhalational anesthetics are administered in and, for the most part, eliminated via respired air. They serve to maintain anesthesia Pertinent substances are considered on p. 218. 

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. 

The rates of onset and cessation of action vary widely between different inhalational anesthetics and also depend on the degree of lipophilicity. In the case of N2O, there is rapid elimination from the body when the patient is ventilated with normal air. Due to the high partial pressure in blood, the driving force for transfer of the drug into expired air is large and, since tissue uptake is minor, the body can be quickly cleared of N2O. 

It is suspected that these drugs selectively bind with the intracellular surface of sodium channels and block the entrance of sodinm ions into the cell. This leads to stoppage of the depolarization process, which is necessary for the diffusion of action potentials, elevation of the threshold of electric nerve stimulation, and thus the elimination of pain. Since the binding process of anesthetics to ion channels is reversible, the drug diffuses into the vascular system where it is metabolized, and nerve cell function is completely restored. 

Contemporary anesthetic management requires (1) rapid loss of consciousness, which eliminates awareness, memory of pain, anxiety, and stress throughout the surgical period (2) a level of analgesia sufficient to abohsh the reflex reactions to pain, such as muscular movement and cardiovascular stimulation (3) minimal and reversible influence on vital physiological functions, such as those performed by the cardiovascular and respiratory systems (4) relaxation of skeletal muscle to facilitate endotracheal intubation, provide the surgeon ready access to the operative field, and reduce the dose of anesthetic required to produce immobihty (5) lack of... 

The initial unequal tissue-drug distribution cannot persist, however, because physicochemical forces tend to require an eventual establishment of concentration equilibria with other less well perfused organs. Therefore, as the drug continues to be removed from the blood by the less richly perfused tissues or eliminated by metabolism and excretion or both, plasma levels will fall, and the concentration of anesthetic in the brain will decline precipitously. 

The use of inhalational anesthetics is generally reserved for maintenance of anesthesia. The development of an anesthetic concentration in the brain occurs more slowly with inhalational anesthetics than with IV drugs. Once an anesthetic level has been achieved, however, it is easily adjusted by controlling the rate or concentration of gas delivery from the anesthesia machine. The rate of recovery from a lengthy procedure in which inhalational agents are used is reasonably rapid, since inhalational anesthetics are eliminated by the lungs and do not depend on a slow rate of metabolism for their tissue clearance. Thus, inhalational drugs meet the requirement for a relatively prompt return of the patient s psychomotor competence. 

Various anesthetic agents require widely different partial pressures to produce the same depth of anesthesia (Table 25.2). Methoxyflurane, for example, with a MAC of 0.16%, is the most potent agent listed in the table. Only 0.16% of the molecules of inspired gas need be methoxyflurane. N2O is the least potent agent, with a MAC that exceeds 100%. Thus, a level of unconsciousness needed to eliminate movement is seldom achieved with N2O. 

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