Nervous system recovery

These drug have a rapid onset and a short duration of action. They depress the central nervous system (CNS) to produce hypnosis and anesthesia but do not produce analgesia. Recovery after a small dose is rapid. 

Signs and Symptoms Typically biphasic, the first phase consists of nonspecific flu-like symptoms that last about a week. This is followed by a 1-7 day asymptomatic period. The third and final phase is an abrupt onset of encephalitis, which affects the central nervous system phase producing tremors, dizziness, and altered sensorium. Recovery is prolonged. 

Signs and Symptoms Symptoms include sudden onset of intense headache, fever, nausea, vomiting, and sensitivity to light (photophobia) followed by central nervous system abnormalities such as stupor, tremors, delirium, focal epilepsy and flaccid paralysis (especially in the shoulder), and coma. Recovery is prolonged. Sequelae may include paralysis of the upper extremities and back. 

Some aspects of multiple sclerosis are reflected in the animal model experimental autoimmune encephalomyelitis, which is induced by immunization of susceptible animals with appropriate encephalogenic proteins or peptides. In these animals, if cultured adult stem cell neurospheres are injected into the bloodstream, injected cells can find their way to damaged portions of the nervous system and improve function in mice. How the injected cells augmented the recovery process is unclear. One possibility is that cells recruited to the lesions differentiated into oligodendrocytes and generated new myelin sheaths, but this seems unlikely in the face of ongoing cellular destruction. 

Compensatory plasticity and functional recovery can be enhanced in the injured adult central nervous system through blockade of Nogo-A 525... 

Acute Exposure If recovery from nerve agent poisoning occurs, it will be complete unless anoxia or convulsions have gone unchecked so long that irreversible central nervous system changes due to anoxemia have occurred. 

The most serious toxicological effect of endrin is central neurotoxicity (Klaasen et al. 1986). Organo-chlorines interfere with the normal flux of cations across the axon, disrupting central nervous system homeostasis (Finkel 1983 Klaasen et al. 1986). Endrin is one of the most toxic cyclodienes, and seizure activity may develop rapidly after exposure (Proctor et al. 1988). In most cases, recovery is rapid. However, headaches, dizziness, weakness, and anorexia may persist for 2-4 weeks. 

Pathological changes that may occur in the central nervous system during acute exposure to high doses may complicate recovery. Severe Parkinsonism was one of the effects noted in four case reports resulting from severe acute oral exposure to cyanide (Carella et al. 1988 Grandas et al. 1989 Rosenberg et al. 

Repeated dose chronic toxicity studies are performed on two species of animals a rodent and nonrodent. The aim is to evaluate the longer-term effects of the drug in animals. Plasma drug concentrations are measured and pharmacokinetics analyses are performed. Vital functions are studied for cardiovascular, respiratory, and nervous systems. Animals are retained at the end of the study to check toxicity recovery. Table 5.2 shows the duration of the animal studies, which depends on the duration of the intended human clinical trial. Appendix 6 summarizes the information to be submitted to regulatory authorities. 

McGeachy MJ, Stephens LA, Anderton SM Natural recovery and protection from autoimmune encephalomyelitis contribution ofCD4+CD25+ regulatory cells within the central nervous system. J Immunol 2005 175 3025-3032. 

Cumulative toxic effects occurred in various animal species receiving repeated small doses of decaborane by oral, intraperitoneal, or cutaneous routes. The rate of recovery was markedly delayed in some animal species surviving repeated doses compared with those that had received a single, large dose. In dogs repeatedly given oral doses of 3mg/kg, the effects on the central nervous system were not pronounced but there was damage to the liver and kidneys. 

The LCso for rats was 1230ppm for 36 minutes effects included lacrimation, rhinor-rhea, gasping, and cyanosis. Pulmonary edema was present at autopsy. At 300ppm, all rats died within 40-90 minutes, whereas exposure to 33 ppm caused deaths in 3-10 hours. Exposure to 6.35 ppm 6 hours/day, 5 days/week, for 6 months resulted in death of 11 of 19 rats similar exposure in dogs caused mild symptoms the first 2 days, followed by complete recovery In three species of animals, intravenous injection caused methemoglobinema, anemia, damage to the central nervous system, and pulmonary edema. ... 

Reversibility of Noncarcinogenic Systemic Effects. Most case reports of humans intoxicated with carbon tetrachloride indicate that, if death can be averted, clinical signs of renal and hepatic dysfunction diminish within 1-2 weeks, and recovery often appears to be complete. This is primarily because both liver and kidney have excellent regenerative capacity and can repair injured cells or replace dead cells (Dragiani et al. 1986 Norwood et al. 1950). However, high doses or repeated exposure can lead to fibrosis or cirrhosis that may not be reversible. The depressant effects of carbon tetrachloride on the central nervous system do appear to be reversible, although any neural cell death that occurs (Cohen 1957) is presumably permanent. 

Neuromuscular paralysis occurs 12 to 36 hours after ingestion of the toxin. Early symptoms include diplopia, dysphagia, and dysarthria. Paralysis may descend to include proximal and limb muscles and result in dyspnea and respiratory depression. The toxins do not cross the placental barrier but do enter the central nervous system (CNS). PupU size may or may not be normal, but mental and sensory functions are not impaired. Recovery from paralysis requires days to weeks. 

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