Toxicity reactions

The reaction with sodium sulfite or bisulfite (5,11) to yield sodium-P-sulfopropionamide [19298-89-6] (C3H7N04S-Na) is very useful since it can be used as a scavenger for acrylamide monomer. The reaction proceeds very rapidly even at room temperature, and the product has low toxicity. Reactions with phosphines and phosphine oxides have been studied (12), and the products are potentially useful because of thek fire retardant properties. Reactions with sulfide and dithiocarbamates proceed readily but have no appHcations (5). However, the reaction with mercaptide ions has been used for analytical purposes (13)). Water reacts with the amide group (5) to form hydrolysis products, and other hydroxy compounds, such as alcohols and phenols, react readily to form ether compounds. Primary aUphatic alcohols are the most reactive and the reactions are compHcated by partial hydrolysis of the amide groups by any water present. 

Several species of the moray eel (Gymnothorax) have caused toxic reactions, especially ki Japan. The toxic principle appears to be protekiaceous and is found predominately ki the blood but it may occur ki the flesh as well. Its exact stmcture remains somewhat uncertain. 

Although the antibacterial spectmm is similar for many of the sulfas, chemical modifications of the parent molecule have produced compounds with a variety of absorption, metaboHsm, tissue distribution, and excretion characteristics. Administration is typically oral or by injection. When absorbed, they tend to distribute widely in the body, be metabolized by the Hver, and excreted in the urine. Toxic reactions or untoward side effects have been characterized as blood dyscrasias crystal deposition in the kidneys, especially with insufficient urinary output and allergic sensitization. Selection of organisms resistant to the sulfonamides has been observed, but has not been correlated with cross-resistance to other antibiotic families (see Antibacterial AGENTS, synthetic-sulfonamides). 

Purification. Hemoglobin is provided by the red blood ceU in highly purified form. However, the red ceU contains many enzymes and other proteins, and red ceU membranes contain many components that could potentially cause toxicity problems. Furthermore, plasma proteins and other components could cause toxic reactions in recipients of hemoglobin preparations. The chemical modification reactions discussed herein are not specific for hemoglobin and may modify other proteins as well. Indeed, multifimctional reagents could actually couple hemoglobin to nonhemoglobin proteins. 

The side effects and toxic reactions to verapamil iaclude upper GI upset, constipation, di22iaess, headaches, flushing and burning, edema, hypotension, bradycardia, and various conduction disturbances. Verapamil has negative iaotropic activity and may precipitate heart failure ia patients having ventricular dysfunction (1,2). 

For enzymes intended for parenteral use, the manufacturer must assure that the enzyme preparation is essentially pure and free of endotoxins. Electrophoretic and immunologic tests provide the requisite evidence of purity and homogeneity. Most importandy, the manufacturer must remove toxic impurities, eg, bacterial hpopolysacchati.de (endotoxins) which might cause severe toxic reactions such as anaphylactic shock, fever, and vascular coUapse. 

The importance of the penicillins as a class of heterocyclic compounds derives primarily from their effectiveness in the treatment of bacterial infections in mammals (especially humans). It has been estimated that, in 1980, the worldwide production of antibiotics was 25 000 tons and, of this, approximately 17 000 tons were penicillins (81MI51103). The Food and Drug Administration has estimated that, in 1979 in the U.S.A., 30.1 x 10 prescriptions of penicillin V and 44.3 x 10 prescriptions of ampicillin/amoxicillin were dispensed. This level of usage indicates that, compared to other methods of dealing with bacterial infection, the cost-benefit properties of penicillin therapy are particularly favorable. Stated differently, penicillin treatment leads to the elimination of the pathogen in a relatively high percentage of cases of bacterial infection at a relatively low cost to the patient in terms of toxic reactions and financial resources. 

Fumigation with ethylene oxide does indeed lead to a considerable reduction in the germ count (and at the same time destruction of insects), but the process, because of the formation of toxic reaction products (ethylene chlorhydrin, ethylene glycol) has been banned throughout the European Community since 01.01.1990 Ionizing irradiation a declaration of the treatment is obligatory, but such drugs find little acceptance by the public who expect nature s products as such. 

Halogenation The commercially important halogens are chlorine, bromine, fluorine, iodine. Refer to Table 5.19 for properties All are highly toxic Reactions are highly exothermic and chain reactions can occur, which may result in detonation... 

A toxic reaction may take place during or soon after exposure, or it may only appear after a latency period. Chronic toxicity requires exposure of several years for a toxic effect to occur in humans. With respect to experimental animals, the animals are usually exposed for most or all of their life time to ascertain the occurrence of chronic toxicity. Acute toxic reactions that occur immediately are easy to associate with the exposure and the exposure-effect relationship can readily be demonstrated. The longer the time interval between exposure and effect, the more difficult it is to delineate the relationship between exposure and effect. 

There are some basic differences between toxic and allergic reactions. The most important differences are (1) an allergic reaction always requires a prior exposure to the compound, and this reaction only occurs in sensitized individuals and (2) a dose-response relationship is characteristic to a toxic reaction, whereas such a relationship is much less clear for an allergic reaction. Even minute doses can elicit an allergic reaction in a sensitized individual (see Fig. 5.42). ... 

Paracelsus, a Swiss physician of the sixteenth century, stated that everything is toxic, it is just the dose that matters. This statement still holds true 500 years after Paracelsus developed it to defend the use of toxic compounds such as lead and mercury in the treatment of serious diseases such as syphilis. Chemical compounds cause their toxic effects by inducing changes in cell physiology and biochemistry, and an understanding of cellular biology is a prerequisite if one wishes to understand the nature of toxic reactions. 

Toxic reactions occur by several mechanisms activation of metabolism, production of reactive intermediates and subsequent reactions with cell macromolecules, changing receptor responses, or through abnormal defence reactions. Several compounds cause toxicity by mimicking the organism s own hormones or neurotransmitters, or activating the body s endogenous receptors in some non-physiological way. ... 

Toxic Reactions of the Skin Irritation is the most common reaction of the skin. Skin irritation is usually a local inflammatory reaction. The most common skin irritants are solvents dehydrating, oxidizing, or reducing compounds and cosmetic compounds. Acids and alkalies are common irritants. Irritation reactions can be divided into acute irritation and corrosion. Necrosis of the surface of the skin is typical for corrosion. Acids and alkalies also cause chemical burns. Phenols, organotin compounds, hydrogen fluoride, and yellow phosphorus may cause serious burns. Phenol also causes local anesthesia, in fact it has been used as a local anesthetic in minor ear operations such as puncture of the tympanous membrane in cases of otitis. ... 

Light and Toxic Reactions In many individuals, exposure to ultraviolet radiation from the sun causes skin reactions such as erythema, thickening of the epidermis, and darkening of existing pigment. Exposure to ultraviolet light also increases the risk of different forms of skin cancers, especially malignant melanoma. ... 

An academy of physicians that promotes a better understanding of ecologic illness and seeks methods for controlling such illness. Studies and treats people with illnesses or health problems caused by adverse, allergic or toxic reactions to a wide variety of environmental substances. 

In vitro studies in human liver fractions indicated that azacitidine may be metabolized by the liver. Azacitidine and its metabolites are known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. 

Nurses must carefully monitor the patient s blood levels of drugs to ensure that they remain within the therapeutic range Any deviation should be reported to the primary health care provider. Because some dragp can cause toxic reactions even in recommended doses, the nurse should be aware of the signs and symptoms of toxicity of commonly prescribed drugs. 

The adverse reactions seen with penicillamine include pruritus, rash, anorexia, nausea, vomiting, epigastric pain, bone marrow depression, proteinuria, hematuria, increased skin friability, and tinnitus. Penicillamine is capable of causing severe toxic reactions. 

Toxic reactions are possible when taking gold compounds. Report adverse reactions to the primary health care provider as soon as possible ... 

Penicillamine. The primary healHi care provider will explain Hie treatment regimen and adverse reacHons before therapy is started. You must know which toxic reactions require contacting Hie primary healHi care provider immediately. Take penicillamine on an empty stomach, 1 hour before or 2 hours after a meal. If other drugp are prescribed, penicillamine is taken 1 hour apart from any other drug. Observe skin areas over Hie elbows, shoulders, and buttocks for evidence of bruising, bleeding, or break in the skin (delayed wound healing may occur). If Hiese occur, do not self-treat the... 

MONITORING AND MANAGING RESPIRATORY DEPRESSION These drugs depress the CNS and can cause respiratory depression. The nurse carefully assesses respiratory function (rate, depth, and quality) before administering a sedative, Vs, to 1 hour after administering the drug, and frequently thereafter. Toxic reaction of the barbiturates can cause severe respiratory depression, hypoventilation, and circulatory collapse. 

Lithium carbonate is rapidly absorbed after oral administration. The most common adverse reactions include tremors, nausea, vomiting, thirst, and polyuria Toxic reactions may be seen when serum lithium levels are greater than 1.5 mEq/L (Table 32-1). Because some of these toxic reactions are potentially serious, lithium blood levels are usually obtained during therapy, and the dosage of lithium is adjusted according to the results. 

AnUine, however, is too toxic for use in mbber products. Its less toxic reaction product with carbondisulfide, thiocarbanihde, was introduced as an accelerator in 1907. Further developments led to guanidine accelerator [4]. Reaction products formed between carbon disulfide and aliphatic amines (dithiocarbamates) were first used as accelerators in 1919 [5]. These were and still are the most active accelerators in respect to both cross-finking rates and extent of cross-link formation. However, most dithiocarbamates accelerators give little or no scorch resistance and therefore cannot be used in aU applications. 

The effects of protein deficiency on endosulfan toxicity were studied in Wistar rats (Boyd and Dobos 1969 Boyd et al. 1970). Rats fed a diet totally deficient in protein for 28 days prior to administration of a single oral dose of endosulfan had an LDjq of 5.1 mg/kg of endosulfan. Rats fed a low-protein diet (3.5% protein) for 28 days had an LDjq of 24 mg/kg of endosulfan. Rats fed standard laboratory chow (26% protein) had an LDjq of 102-121 mg/kg. The immediate cause of death in all animals was respiratory failure following tonic-clonic convulsions. This study demonstrated that, while a protein-deficient diet does not affect the nature of the toxic reaction, it may affect the sensitivity of rats to the lethal effects of endosulfan. 

Not all symptoms after RCM exposure do resemble a hypersensitivity reaction. Toxic reactions related to the toxicity of RCM, imspecific reactions of unknown origin and or factors unrelated to RCM, such as chronic idiopathic urticaria, may occur (fig. 1) [3]. Hypersensitivity reactions to RCM may both present either under the clinical picture of anaphylaxis with the potential to result in fataUties or as delayed occurring... 

The well-known adverse reaction formerly often observed after intramuscular injection of clemizol penicilUn in the treatment of syphilis with anaphylaxis-like symptoms plus CNS involvement in the absence of immimological sensitization to penicillin was called the Hoigne syndrome or embolic-toxic reaction, and might be explained by intravasal appUcation of LA with subsequent toxic effects [8]. 

The different solubilities of these two kinds of vitamins have important metabolic consequences. Aqueous body fluids do not dissolve fat-soluble vitamins, so these molecules can be stored in fatty body tissue for a long time. As a result, too much of a fat-soluble vitamin can overload the body s storage capabilities and lead to a toxic reaction. In contrast, the body cannot store water-soluble vitamins instead, it excretes anything more than the amount it can use immediately. People must therefore have a steady supply of water-soluble vitamins in their diets to remain healthy. 

Regrettably, all chemotherapeutic agents have the potential to produce adverse reactions with varying degrees of frequency and severity, and these include hypersensitivity reactions and toxic effects. These may be dose-related and predictable in a patient with a history of hypersensitivity or a previous toxic reaction to a drug or its chemical analogues. However, many adverse events are idiosyncratic and therefore unpredictable. 

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