Blood solubility

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... 

Other important determinants of the effects of compounds, especially solvents, are their partition coefficients, e.g., blood-tissue partition coefficients, which determine the distribution of the compound in the body. The air-blood partition coefficient is also important for the absorption of a compound because it determines how quickly the compound can be absorbed from the airspace of the lungs into the circulation. An example of a compound that has a high air-blood partition coefficient is trichloroethane (low blood solubility) whereas most organic solvents (e.g., benzene analogues) have low air-blood partition coefficients (high blood solubility). 

Pulmonary excretion takes place for volatile compounds. Alveolar air is at equilibrium with capillary blood. Thus, pulmonary excretion depends on the vapor pressure of the compound and its blood solubility. If blood solubility is... 

Frequently it is desirable to overcome the slow rate of rise of alveolar tension associated with such factors as the high blood solubility of some anesthetics and increased pulmonary blood flow. Since both of these factors retard tension development by increasing the uptake of anesthetic, the most effective way to alleviate the problem is to accelerate the input of gas to the alveoli. A useful technique to increase the input of anesthetic to the lung is to elevate the minute alveolar ventilation. This maneuver, which causes a greater quantity of fresh anesthetic gas to be delivered to the patient per unit of time, is most effective with highly soluble agents (Fig. 25.4). 

Sevoflurane (Ultane) is the most recently introduced inhalation anesthetic. It has low tissue and blood solubility, which allows for rapid induction and emergence and makes it useful for outpatient and ambulatory procedures. It has the advantage of not being pungent, a characteristic that permits a smooth inhalation induction, and is particularly useful in pediatric anesthesia. 

One of the most important factors influencing the transfer of an anesthetic from the lungs to the arterial blood is its solubility characteristics (Table 25-2). The blood gas partition coefficient is a useful index of solubility and defines the relative affinity of an anesthetic for the blood compared with that of inspired gas. The partition coefficients for desflurane and nitrous oxide, which are relatively insoluble in blood, are extremely low. When an anesthetic with low blood solubility... 

The concentration of an inhaled anesthetic in the inspired gas mixture has direct effects on both the maximum tension that can be achieved in the alveoli and the rate of increase in its tension in arterial blood. Increases in the inspired anesthetic concentration increase the rate of induction of anesthesia by increasing the rate of transfer into the blood according to Fick s law (see Chapter 1). Advantage is taken of this effect in anesthetic practice with inhaled anesthetics that possess moderate blood solubility (eg, enflurane, isoflurane, and halothane). For example, a 1.5% concentration of isoflurane may be administered initially to increase the rate of rise in the brain concentration the inspired concentration is subsequently reduced to 0.75-1% when an adequate depth of anesthesia is achieved. In addition, these moderately soluble anesthetics are often administered in combination with a less soluble agent (eg, nitrous oxide) to reduce the time required for loss of consciousness and achievement of a surgical depth of anesthesia. 

An increase in pulmonary blood flow (increased cardiac output) slows the rate of rise in arterial tension, particularly for those anesthetics with moderate to high blood solubility. This is because increased pulmonary blood flow exposes a larger volume of blood to the anesthetic thus, blood "capacity" increases and the anesthetic tension rises slowly. A decrease in pulmonary blood flow has the opposite effect and increases the rate of rise of arterial tension of inhaled anesthetics. In a patient with circulatory shock, the combined effects of decreased cardiac output (resulting in decreased pulmonary flow) and increased ventilation will accelerate the induction of anesthesia with halothane and isoflurane. This is not likely to occur with nitrous oxide, desflurane, or sevoflurane because of their low blood solubility. 

Anaesthetic gases such as ether which have a high blood solubility (Ostwald solubility coefficient in blood is 12) are transported away from the lungs more rapidly than those such as halothane (Ostwald coefficient = 2.3) and nitrous oxide (Ostwald coefficient = 0.47). As... 

Increases in blood solubility without corresponding increases in tissue solubility slow the rate at which halothane increases in the alveoli. Because of the increased content of this anaesthetic in the blood flowing through the tissues, however, the halothane partial pressure in the tissues approaches equilibrium more rapidly than in the alveoli. The net consequence is that the time for induction with halothane is not greatly affected by changes in blood solubility, although the... 

Studies in humans and animals have shown that Stoddard Solvent is readily absorbed through the lungs. In general, the aromatic components are likely to be more completely absorbed due to their higher blood/gas solubility. It is expected that volatile components or metabolites of Stoddard Solvent that have low blood solubility would be most easily excreted in exhaled breath. Aromatic components would be expected to be excreted primarily in urine as metabolites. 

Amidases Liver, other tissues (not active in blood) Soluble fraction of cells... 

Long-chain and branched hydrocarbons that are primary components of JP-8, include -nonanc, -dccanc, -dodccanc, -tridecane, isopropylbenzene, -propylbcnzcnc, trirnethylbenzene, -dimcthylbenzene, naphthalene, n-pentylbenzene, and -tricthylbcnzcnc. Inhaled long-chain aliphatic hydrocarbons generally show poor blood uptake because of lower blood solubility. They have relatively high lipid blood partition coefficients this can result in accumulation in lipid-rich tissues, such as brain and fat. In laboratory studies, brain concentrations of hydrocarbons and their metabolites greatly exceed their plasma concentrations. 

Pulmonary blood flow At high pulmonary blood flows, the gas partial pressure rises at a slower rate thus, the speed of onset of anesthesia is reduced. At low flow rates, onset is faster. In circulatory shock, this effect may accelerate the rate of onset of anesthesia with agents of high blood solubility. 

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