Nervous system toxicity secondary effects

A variety of adverse effects have been reported following the use of antacids. If sodium bicarbonate is absorbed, it can cause systemic alkalization and sodium overload. Calcium carbonate may induce hypercalcemia and a rebound increase in gastric secretion secondary to the elevation in circulating calcium levels. Magnesium hydroxide may produce osmotic diarrhea, and the excessive absorption of Mg++ in patients with renal failure may result in central nervous system toxicity. Aluminum hydroxide is associated with constipation serum phosphate levels also may become depressed because of phosphate binding within the gut. The use of antacids in general may interfere with the absorption of a number of antibiotics and other medications. 

According to Powell and Chen, gramine, used as the unstable hydrochloride, m.p. 191° (dec.), raises the blood pressure in anaesthetised cats in Small doses, but lowers it in doses of 30 to 40 mgm. per kilo., with a secondary rise. It reduces the chief effects of adrenaline without reversal. The toxic dose for rats is about 63 mgm./kilo. Supniewski and Serafinowna state that gramine excites the central nervous system in mammals, but in large doses causes paralysis. At 1 in 25,000 it causes contraction of the isolated uterus. 

Almost all systemic effects of methyl parathion are related to the action of this compound on the nervous system or are secondary to this primary action. It is therefore necessary to preface a description of the mechanisms of toxicity of methyl parathion with a brief discussion of the nervous system and neuro-humoral transmitters (excerpted from Lefkowitz et al. 1996). 

Cardiovascular Effects. Most studies of humans exposed to carbon tetrachloride by inhalation have not detected significant evidence of cardiovascular injury, even at exposure levels sufficient to markedly injure the liver and/or kidney. Changes in blood pressure, heart rate, or right- sided cardiac dilation have sometimes, but not always, been observed (Ashe and Sailer 1942 Guild et al. 1958 Kittleson and Borden 1956 Stewart et al. 1961 Umiker and Pearce 1953), and are probably secondary either to fluid and electrolyte retention resulting from renal toxicity, or to central nervous system effects on the heart or blood vessels. Carbon tetrachloride also may have the potential to induce cardiac arrhythmias by sensitizing the heart to epinephrine, as has been reported for various chlorinated hydrocarbon propellants (Reinhardt et al. 1971). 

Drug interactions Proleukin may affect central nervous system function. Therefore interactions could occur following concomitant administration of psychotropic drugs. Concurrent administration of drugs possessing nephrotoxic, myelotoxic, cardiotoxic, or hepatotoxic effects with Proleukin may increase toxicity in these organ systems. Reduced kidney and liver function secondary to Proleukin treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs. Beta-blockers and other antihypertensives may potentiate the hypotension seen with Proleukin. 

In its acute stages, benzene toxicity appears to be due primarily to the direct effects of benzene on the central nervous system, whereas the peripheral nervous system appears to be the target following chronic low-level exposures. In addition, because benzene may induce an increase in brain catecholamines, it may also have a secondary effect on the immune system via the hypothalamus-pituitary-adrenal axis (Hsieh et al. 1988b). Increased metabolism of catecholamines can result in increased adrenal corticosteroid levels, which are immunosuppressive (Hsieh et al. 1988b). 

High blood levels after topical application or injection of anesthetics may potentially cause systemic reactions. Toxic effects may appear in the central nervous system (CNS), cardiovascular system, or respiratory system. CNS toxicity appears initially as stimulation and may manifest itself clinically as nervousness, tremors, or convulsions. CNS depression, observed clinically as loss of consciousness and depression of respiration, usually follows. The earliest signs of cardiovascular involvement are hypertension, tachycardia, and, occasionally, cardiac arrhythmias. Late cardiovascular signs are hypotension, absent pulse, and weak or absent heartbeat. The effects on the cardiovascular system can develop either simultaneously with CNS depression or alone. If allowed to continue, such cardiac depression and resultant peripheral vasodilation are followed by secondary respiratory failure. 

NOTE For these categories the specific target organ/system that has been primarily affected by the classified substance may be identified, or the substance may be identified as a general systemic toxicant. Attempts should be made to determine the primary target organ of toxicity and classify for that purpose, e.g. hepatoxicants, neurotoxicants. One should carefully evaluate the data and, where possible, not include secondary effects, e.g. a hepatotoxicant can produce secondary effects in the nervous or gastro-intestinal systems. ... 

The primary clinical effects observed in beta blocker toxicity are cardiovascular in nature. Direct cardiac effects include bradycardia (sinus, atrioventricular node, and ventricular), all degrees of atrioventricular block, bundle branch blocks, and asystole. Ventricular arrhythmias may occur secondary to bradycardia. Torsades de pointes has been associated with chronic toxicity from sotalol. Hypotension occurs and is due to decreased cardiac output and/or vasodilation. Central nervous system effects of these drugs including lethargy, coma, and seizures are secondary to the cardiovascular toxicities. Seizures and coma may be secondary to hypoglycemia. Bronchospasm can occur secondary to beta-2 blockade. Hypoglycemia and hyperkalemia can occur. 

From the standpoint of screening and hazard identification, a notable point relating to the interpretation of data from FOB and motor activity studies is whether the effects observed in response to toxicant exposure represent a direct effect of the toxicant on the nervous system or are secondary to changes in other systems since such apical tests rely on the functional integrity of multiple systems. In some circumstances, the fact that the toxic effect is ultimately expressed in behavior may minimize the importance... 

When a toxicant is introduced, activity may increase, decrease, or remain unchanged depending on choice of apparatus, age of the animal, the relative novelty and complexity of the environment, and many other variables. Although a change in an animal s activity as a result of its exposure to a toxicant indicates a change in the function of its nervous system, interpretation is not straightforward. The change can be due to the toxicant s primary effect on nervous system function or to its effect on some other system that results in a secondary effect on nervous system function. Certainly, extrapolation from activity measurements in rodents to such phenomena as hyperactivity in children is unwarranted,... 

Dietary exposure of rats to 2.2 mg Hg/kg/day as mercuric chloride for 3 months resulted in inactivity and abnormal gait (Goldman and Blackburn 1979). However, it is unclear whether the effects observed in this study were the direct result of effects on the nervous system, or whether they may have been secondary to other toxic effects. No evidence of neurotoxicity (clinical signs of neurotoxicity and optic and peripheral nerve structure) was seen in mice administered 0.74 or 2.2 mg Hg/kg/day as mercuric chloride in the drinking water for 110 days (Ganser and Kirschner 1985). The investigators increased the... 

CN intoxication may result in morphological and functional adverse effects in specific organ systems or tissues as a consequence of acute or repeated exposure to CN. These include both direct adverse reactions to and lesions of the respiratory, cardiovascular and central nervous systems. Secondary toxic effects, from SCN, may occur with the thyroid gland. These organ and tissue effects are summarized below. 

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