High lipids

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 amide local anaesthetic lidocaine may also be used as an antianhythmic for ventricular tachycardia and exra-systoles after injection into the blood circulation. Drugs with high lipid solubility such as bupivacaine cannot be used for these purposes because their prolonged binding to the channel may induce dysrhythmias or asystolic heart failure [3]. Systemically applied lidocaine has also been used successfully in some cases of neuropathic pain syndromes [4]. Here, electrical activity in the peripheral nervous system is reduced by used-dependent but incomplete sodium channel blockade. 

Cellular functions are controlled by extracellular signals such as hormones, neurotransmitters, odorants, light and other chemical or physical stimuli. Only a few of these signal molecules, e.g., the highly lipid-soluble steroids or thyroid hormones, can diffiise across the... 

Charney et al. (2001), Harvey (1985), Matthew (1971), and Wesson and Smith (1977) have discussed the pharmacology of barbiturates. Barbiturates are derived from barbituric acid, which is the product of the fusion of malonic acid and urea. Barbituric acid lacks CNS activity. The two main classes of barbiturates are the highly lipid-soluble thiobarbiturates, in which sulfur replaces oxygen at the second carbon atom of the barbituric acid ring, and the less soluble oxybarbiturates, with oxygen at the second carbon atom (Table 3-3). Highly lipid-soluble barbiturates have a more rapid onset, a short duration of action, and greater potency than those with lower lipid solubility. 

Death from overdose of barbiturates may occur and is more likely when more than 10 times the hypnotic dose is ingested. The barbiturates with high lipid solubility and short half-lives are the most toxic. Thus the lethal dose of phenobarbital is 6—10 g, whereas that of secobarbital, pentobarbital, or amo-barbital is 2-3 g. Symptoms of barbiturate poisoning include CNS depression, coma, depressed reflex activity, a positive Babinski reflex, contracted pupils (with hypoxia there may be paralytic dilation), altered respiration, hypothermia, depressed cardiac function, hypotension, shock, pulmonary complications, and renal failure. 

Diprivan) 40 mg every 1 0 seconds titrated to EEG) depression intubation high lipid load (increased calories) propofol infusion syndrome... 

A discussion of all the reasons for this phenomenon is beyond the scope of this chapter, but a simple example will illustrate the concept. Highly lipid-soluble drugs, such as pentobarbital, are preferentially distributed into adipose tissue. The result is that plasma concentrations are extremely low after distribution is complete. When the apparent volumes of distribution are calculated, they are frequently found to exceed total body volume, occasionally by a factor of 2 or more. This would be impossible if the concentration in the entire body compartment were equal to the plasma concentration. Thus, Vd is an empirically fabricated number relating the... 

In mixtures containing high lipid water ratios, HC1 will appreciably partition into solutions with pH <2.5, as will KOH when pH >11.5 [162,284]. General box diagrams reflecting these caveats have been discussed [275]. 

Note, a. Defined as drugs that make one feel better rather than just well, for example, drugs for treating impotence, high lipids or menopause symptoms, and contraceptives. 

Compounds with a high H-bond acceptor potential (EUh > 8) (e.g., cyclosporine A, SDZ PSC-833) act as competitive inhibitors, presumably because they occupy all H-bond donor sites of the transporter. Due to the strong interaction of these compounds with P-gp they are transported slowly, and this is reflected in a low rate of ATP hydrolysis. Many of these compounds exhibit high lipid/water partition coefficients and thus also low K, values. 

In this study a ten year model simulation with the fully coupled ocean-atmosphere GCM [Roeckner et al (2003), Marsland et al (2003), Maier-Reimer et al (2005), Lammel et al (2001)] was performed. The insecticide DDT was chosen because it is one of the most studied of all synthetic organic chemicals and because of its physicochemical properties. It has a low water solubility, high lipid solubility and it is semi-... 

As mentioned earlier, ascorbate and ubihydroquinone regenerate a-tocopherol contained in a LDL particle and by this may enhance its antioxidant activity. Stocker and his coworkers [123] suggest that this role of ubihydroquinone is especially important. However, it is questionable because ubihydroquinone content in LDL is very small and only 50% to 60% of LDL particles contain a molecule of ubihydroquinone. Moreover, there is another apparently much more effective co-antioxidant of a-tocopherol in LDL particles, namely, nitric oxide [125], It has been already mentioned that nitric oxide exhibits both antioxidant and prooxidant effects depending on the 02 /NO ratio [42]. It is important that NO concentrates up to 25-fold in lipid membranes and LDL compartments due to the high lipid partition coefficient, charge neutrality, and small molecular radius [126,127]. Because of this, the value of 02 /N0 ratio should be very small, and the antioxidant effect of NO must exceed the prooxidant effect of peroxynitrite. As the rate constants for the recombination reaction of NO with peroxyl radicals are close to diffusion limit (about 109 1 mol 1 s 1 [125]), NO will inhibit both Reactions (7) and (8) and by that spare a-tocopherol in LDL oxidation. 

Tetraalkylleads are highly lipid, soluble, rapidly metabolized and readily cross the blood-brain barrier. These physicochemical properties make the central nervous system the main site of the toxic action of the alkyllead species138. The earliest symptoms include insomnia, which may be followed by lack of appetite, nausea, vomiting, diarrhea hallucinations, delusions, delirium and ultimately death141. Continuing exposure may lead to complaints associated with central nervous system disturbances141. 

PAHs are widely distributed in the environment as evidenced by their detection in sediments, soils, air, surface waters, and plant and animal tissues. However, the ecological impact of PAHs is uncertain. PAHs show little tendency for bioconcentration despite their high lipid solubility (Pucknat 1981), probably because most PAHs are rapidly metabolized. Sims and Overcash (1983) list a variety of research needs regarding PAHs in soil-plant systems. Specifically, research is needed to establish the rates of PAH decomposition in soils the soil PAH levels above which PAH constituents adversely affect the food chain and enhancement factors that increase degradation rates of PAHs, especially PAHs with more than three rings. Once these factors have been determined, PAH disposal into soils may become feasible at environmentally nonhazardous levels. 

Nimodipine may be more effective than verapamil for rapid-cycling bipolar disorder because of its anticonvulsant properties, high lipid solubility, and good penetration into the brain. 

There are two reasons to think this situation might occur. The first reason is experimental. As discussed in Sections 2-5, in most experiments on chiral materials, tubules and helical ribbons are observed with only one sense of handedness. However, there are a few exceptions in experiments on diacetylenic phospholipids,144 diacetylenic phosphonate lipids,145 146 and bile.162 In these exceptional cases, some helices are observed with the opposite sense of handedness from the majority. In the work on diacetylenic phospholipids, the minority handedness was observed only during the kinetic process of tubule formation at high lipid concentration,144 which is a condition that should promote metastable states. Hence, these experiments may indeed show a case of biased chiral symmetry-breaking in which the molecular chirality favors a state of one handedness and disfavors a mirror image state. 

The physicochemical properties of both PCDD/PCDFs and coplanar PCBs enable these compounds to be readily absorbed by organisms. The high lipid solubility and low water solubility of all congeners lead to the retention of the compounds in... 

Avoid contamination by modern high lipid samples, e.g., keep ancient samples separate from modern samples (store and post separately) and avoid contact with other sources of oil (lunch, car engines, cigars, etc. ) whilst sampling. 

Protein content of field peas is negatively correlated with lipid, cell wall material (CWM), sugar, and ash content and positively correlated with starch separation efficiency and protein separation efficiency in air classification of pea flour. The lower separation efficiency of low protein peas may be due to their high lipid and CWM content which makes disintegration of seeds and separation into protein and starch particles by pin milling difficult. It is suggested that peas with a specific protein content should be used in order to control the protein and starch fraction contents (18). 

The specific mechanisms by which mirex and chlordecone are transferred from the gut, lungs, or skin to the blood are not known. However, mirex is a highly stable, lipophilic compound that is resistant to metabolism. It has a high lipid water partition coefficient, so it partitions readily into fat and demonstrates a very high potential for accumulation in tissues. The preferential distribution of chlordecone to the liver rather than to the fat tissue is due to its association with plasma proteins. 

Distribution. Generally the highest concentration of PCB residues in fish are in tissues of high lipid content. In Table V juvenile coho salmon were fed equal amounts of three chlorobi-phenyls for 117 days. Fish were then killed and lipid content and PCB concentration of various tissues determined (33). Tissues are arranged from top to bottom in order of increasing PCB concentration. For most tissues, but not all, as lipid content increases so does PCB concentration. Lipid content and PCB concentration are low in liver and white muscle, intermediate in spinal column and lateral line muscle, and high in adipose tissue. Lipid content cannot be the sole determinant of PCB concentration in fish tissues because a discrepancy exists between lipid content of brain, heart and spleen and PCB concentration. 

---