Nervous system secondary effects

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. 

Air-poUutant effects on neural and sensory functions in humans vary widely. Odorous pollutants cause only minor annoyance yet, if persistent, they can lead to irritation, emotional upset, anorexia, and mental depression. Carbon monoxide can cause death secondary to the depression of the respiratory centers of the central nervous system. Short of death, repeated and prolonged exposure to carbon monoxide can alter sensory protection, temporal perception, and higher mental functions. Lipid-soluble aerosols can enter the body and be absorbed in the lipids of the central nervous system. Once there, their effects may persist long after the initial contact has been removed. Examples of agents of long-term chronic effects are organic phosphate pesticides and aerosols carrying the metals lead, mercury, and cadmium. 

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). 

Irregular respiration was observed in both male and female rats after a 4-hour nose-only inhalation exposure to aerosolized endosulfan (Hoechst 1983a). In both male and female rats, dyspnea was observed at the lowest concentrations tested (12.3 and 3.6 mg/m for males and females, respectively). Autopsies of the rats that died revealed dark-red, pinhead-sized foci on the lungs. It is unclear whether these effects represent direct effects of inhaled endosulfan on respiratory tissues or whether they are secondary to central nervous system effects on respiratory function. No treatment-related effects were... 

Musculoskeletal Effects. No studies were located regarding musculoskeletal effects in humans after inhalation exposure to trichloroethylene. Trichloroethylene exposure can result in nervous system effects that result in secondary effects on muscle strength, especially in the face (Leandri et al. 1995). See Section 2.2.1.4 for further discussion of nervous system effects following trichloroethylene exposure. 

The actual requirements of the November 8, 2000 ICH guidelines are broadly outlined. They call for the conduct of studies in a core battery to assess effects on the cardiovascular (Table 19.1), respiratory (Table 19.2), central nervous system (Table 19.3) and secondary organ system (Table 19.4) effects. Follow-up studies for the care battery are also required on a case-by-case basis for the three main organ systems. 

Diabetes mellitus can have serious secondary effects. A constantly raised blood sugar level can lead in the long term to changes in the blood vessels (diabetic angiopathy), kidney damage (nephropathy) and damage to the nervous system (neuropathy), as well as to cataracts in the eyes. 

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). 

Because inhalation exposure is unlikely to be directly irritating to the gastrointestinal tract, it is probable that these effects are secondary to effects on the autonomic nervous system (Stewart and Witts 1944). 

The few animal studies located appear to be in general agreement with the human findings (Gardner et al. 1925 Korsrud et al. 1972). Effects of carbon tetrachloride ingestion on blood pressure are sometimes observed, but these are likely secondary to effects on the central nervous system, or to effects on fluid and electrolyte balance following renal injury. 

Gastrointestinal Effects. Humans who ingest oral doses in excess of 30 or 40 mL (680-910 mg/kg) frequently experience nausea, vomiting, and abdominal pain (Hardin 1954 New et al. 1962 Smetana 1939 Umiker and Pearce 1953 von Oettingen 1964). Nausea has been reported after an oral dose of as little as 100 mg/kg (Ruprah et al. 1985). However, these effects are probably secondary to effects on the central nervous system, rather than to a direct effect on the gastrointestinal tract. Oral doses of 3-5 mL (70-110 mg/kg) were widely used in the past for the treatment of hookworms with only mild gastrointestinal distress (Hall 1921 Leach 1922). 

Metabolic Effects. The hyperglycemic effect of nickel is discussed under endocrine effects because it appears to be secondary to the effects on catecholamine release from the adrenal gland and central nervous system and to the effects on insulin release by the pancreas. 

Arterial blood pressure (afterload) is also reduced by propranolol. Although the mechanisms responsible for this antihypertensive effect are not completely understood, they are thought to involve (1) a reduction in cardiac output, (2) a decrease in plasma renin activity, (3) an action in the central nervous system, and (4) a resetting of the baroreceptors. Thus, propranolol may exert a part of its benehcial effects in secondary angina by decreasing three of the major determinants of myocardial oxygen demand, that is, heart rate, contractihty, and systolic wall tension. 

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. 

In biting their food and by means of a relatively small number of gustatory receptor cells, the larvae are informed about the composition of nutrients and secondary plant substances. Taste perception, the integration of sensory information in the insect s central nervous system, is not merely a process of summation. Synergistic as well as antagonistic effects between individual compounds can be observed in the food uptake of larvae on artificial diets. 

---