Central nervous system additive

Recently, leaders in the pharmaceutical industry have developed a list of desired properties for a fourth generation of SERMs (Table 2). In general, future SERMs must oppose endogenous hormone action in the breast and reproductive system while displaying full estrogenic effects in the cardiovasculature, bone and central nervous systems. Additional criteria are that fourth generation compounds possess superior bioavailability compared with existing SERMs and have... 

Solvents vary widely in their toxicological properties. In common they cause dermatitis by removing the natural grease from the skin, and narcosis by acting on the central nervous system additionally some can damage the peripheral nerves, the liver and kidneys and interfere with blood formation and cardiac rhythm. Chlorinated solvents can decompose if exposed to a naked flame to produce acidic fumes (hydrochloric acid and small amounts of phosgene) which are harmful to the lungs. Any harmful effect is related to the amount of solvent absorbed. 

In addition to the weU-defined opioid systems in the central nervous system, the three opioid peptides and their precursor mRNA have also been identified in peripheral tissues. ( -Endorphin is most abundant in the pituitary, where it exists in corticotroph cells with ACTH in the anterior lobe and in melanotroph cells with MSH in the intermediate lobe (59). Enkephalin and pre-pro-enkephalin mRNA have been identified in the adrenal medulla (60) and this has been the source of material for many studies of pro-enkephalin synthesis and regulation. Pre-pro-enkephalin mRNA has also been identified in the anterior and posterior lobes of the pituitary (61). mRNA for all three opioid precursors has been identified in the reproductive system (62—64). POMC... 

Toxicity of 2-Ghloroethanol. Ethylene chlorohydrin is an irritant and is toxic to the Hver, kidneys, and central nervous system. In addition, it is rapidly absorbed through the skin (73). The vapor is not sufficiently irritating to the eyes and respiratory mucous membranes to prevent serious systemic poisoning. Contact of the Hquid in the eyes of rabbits causes moderately severe injury, but in humans corneal bums have been known to heal within 48 hours. Several human fataUties have resulted from inhalation, dermal contact, or ingestion. One fatahty was caused by exposure to an estimated 300 ppm in air for 2.25 hours. In another fatal case, autopsy revealed pulmonary edema and damage to the Hver, kidneys, and brain (73). 

The chromaffin cells of the adrenal medulla may be considered to be modified sympathetic neurons that are able to synthesize E from NE by /V-methylation. In this case the amine is Hberated into the circulation, where it exerts effects similar to those of NE in addition, E exhibits effects different from those of NE, such as relaxation of lung muscle (hence its use in asthma). Small amounts of E are also found in the central nervous system, particularly in the brain stem where it may be involved in blood pressure regulation. DA, the precursor of NE, has biological activity in peripheral tissues such as the kidney, and serves as a neurotransmitter in several important pathways in the brain (1,2). 

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... 

TCDD is the most potent inducer of chloracne. This has been well known since the accident in Seveso, Italy, in 1976 in which large amounts of TCDD were distributed in the environment subsequent to an explosion in a factory that produced a chlorophenoxy herbicide, 2,4,5-T. TCDD is an impurity produced during the production of 2,4,5-T. The most common long-term effect of TCDD exposure was chloracne. Exposed individuals also suffered increased excretion of porphyrins, hyper-pigmentation, central nervous system effects, and liver damage and increased risk of cancer was a long-term consequence of the exposure. In addition to TCDD, polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans, and polychloronaphthalens cause chloracne as well as other effects typical of TCDD. 7i... 

Pentylenetetrazol (188) is a drug with profound stimulatory activity on the central nervous system. As such, the agent was at one time used in shock therapy for treatment of mental disease. Although it has since been supplanted by safer methods, the agents still occupy an important role in various experimental animal models in pharmacology. Addition of hydrazine to the imino ether (186) obtained from caprolactam affords 187. Treat-... 

The blood-brain barrier (BBB) forms a physiological barrier between the central nervous system and the blood circulation. It consists of glial cells and a special species of endothelial cells, which form tight junctions between each other thereby inhibiting paracellular transport. In addition, the endothelial cells of the BBB express a variety of ABC-transporters to protect the brain tissue against toxic metabolites and xenobiotics. The BBB is permeable to water, glucose, sodium chloride and non-ionised lipid-soluble molecules but large molecules such as peptides as well as many polar substances do not readily permeate the battier. 

There is an increased central nervous system (CNS) depressant effect when the skeletal muscle relaxants are administered with other CNS depressants, such as alcohol, antihistamines, opiates, and sedatives. There is an additive anticholinergic effect when cyclobenzaprine is administered with other drugs with anticholinergic effects (eg, antihistamines, antidepressants, atropine, haloperidol). See Chapter 30 for information on diazepam. 

There is an increase in anticholinergic effects when antihistamines are administered with the monamine oxidase inhibitors (MAOIs) and additive sedative effects if administered with central nervous system depressants (eg, narcotic analgesics or alcohol). When cimetidine and loratadine are administered together there is a risk for increased loratadine levels. 

Examples of the xanthine derivatives (drag that stimulate the central nervous system [CNS] resulting in bronchodilation, also called methylxanthines) are theophylline and aminophylline. Additional information concerning the xanthine derivatives is found in the Summary Drag Table Bronchodilators. 

Other central nervous system (CNS) depressants and alcohol may cause additive depressant effects when administered with antitussives containing codeine. 

There is an increased risk for bone marrow suppression when levamisole or hydroxyurea are administered witii other antineoplastic dni. Use of levamisole witii phenytoin increases die risk of phenytoin toxicity. Pegaspargase may alter drug response of the anticoagulants. When procarbazine is administered with other central nervous system (CNS) depressants, such as alcohol, antidepressants, antihistamines, opiates, or the sedatives, an additive CNS effect may be seen. Procarbazine may potentiate hypoglycemia when administered witii insulin or oral antidiabetic dru . ... 

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