Toxicity miosis

TABLE 6.4. Experimental ocular toxicity (miosis) values for G-agents and VX vapor exposures... 

TABLE 9.4 Experimental Ocular Toxicity (Miosis) Values for G-agents and VX Vapor Exposures ... 

Clinical signs and symptoms of toxicity are related to the overstimulation of muscarinic, nicotinic, and central nervous system receptors in the nervous system. Muscarinic receptors are those activated by the alkaloid drug muscarine. These receptors are under the control of the parasympathetic nervous system, and their hyperactivity results in respiratory and gastrointestinal dysfunction, incontinence, salivation, bradycardia, miosis, and sweating. Nicotinic receptors are those activated by nicotine. Hyperactivity of these receptors results in muscle fasciculations even greater stimulation results in blockade and muscle paralysis (Lefkowitz et al. 1996 Tafliri and Roberts 1987). Hyperactivity of central nervous system receptors results in the frank neurological signs of confusion, ataxia, dizziness, incoordination, and slurred speech, which are manifestations of acute intoxication. Muscarine and nicotine are not... 

Respiratory depression, miosis, hypotension, and coma are signs of morphine overdose. While the IV administration of naloxone reverses the toxic effects of morphine, naloxone has a short duration of action and must be administered repeatedly at 30- to 45minute intervals until morphine is cleared from the body. 

Symptoms of overdose with meperidine are qualitatively different from those of morphine in that seizures rather than sedation are common. Respiratory depression and miosis are present. While naloxone reverses overdose-associated toxicity, its use in patients who have received large, frequent doses of meperidine may precipitate seizures. 

Methadone Slow-acting agonist of M-opioid receptor Acute effects similar to morphine (see text) Substitution therapy for opioid addicts High oral bioavailability half-life highly variable among individuals (range 4-130 h) Toxicity Respiratory depression, constipation, miosis, tolerance, dependence, and withdrawal symptoms... 

The toxic effects can be divided into three types as the accumulation of acetylcholine leads to symptoms that mimic the muscarinic, nicotinic, and CNS actions of acetylcholine. Muscarinic receptors for acetylcholine are found in smooth muscles, the heart, and exocrine glands. Therefore, the signs and symptoms are tightness of the chest, wheezing due to bronchoconstriction, bradycardia, and constriction of the pupils (miosis). Salivation, lacrimation, and sweating are all increased, and peristalsis is increased, leading to nausea, vomiting, and diarrhea. 

Physostigmine (eserine sulfate) causes miosis and spasm of accommodation it also lowers intraocular pressure and hence can be used in the treatment of wide-angle glaucoma. As it is lipid soluble, it penetrates into the brain rapidly, raises the acetylcholine concentration and, in toxic amounts, may cause cholinergic CNS toxicity, which is characterized by restlessness, insomnia, tremors, confusion, ataxia, convulsions, respiratory depression, and circulatory collapse. These effects are reversed by atropine. 

Headache, miosis, nervousness, sahvation, diarrhea, respiratory distress, convulsions, coma, cancer, mutagenicity Diarrhea, sahvation, nervousness, respiratory distress, convulsions, chronic toxicity, mutagenicity Cancer, mutagenicity... 

Exposure to acutely toxic concentrations of nerve agents can result in excessive bronchial, salivary, ocular and intestinal secretions, sweating, miosis, bronchospasm, intestinal hypermotility, bradycardia, muscle fasciculations, twitching, weakness, paralysis, loss of consciousness, convulsions, depression of the central respiratory drive, and death (Grob and Harvey, 1953 Grob, 1956 Marrs, 2007 Sidell, 1997 Yanagisawa et al, 2006 many others). Minimal effects observed at low vapor concentrations... 

The results of agent GB vapor exposure studies conducted with human volunteers indicate that the threshold for miosis and other minimal toxic effects falls in the range of 0.05-0.5 mg/m for 10-30 min exposmes (see Table 6.2 and summaries above). 

Recent multiservice (Army, Marine Corps, Navy, and Air Force) guidance on agent-specific exposure limits estimates the VX EC/50 for mild toxicity in humans (miosis, rhinorrhea) to be 0.10 mg VX-min/m for 2-360 min exposures (DA, 2005). The inhalation/ocular ECtso for severe effects in humans (i.e. muscular weakness, tremors, breathing difficulty, convulsions, paralysis) was estimated to be 10 mg-min/m for 2-360 min exposures for a respiratory minute volume of 15 1/min (DA, 2005). 

If liquid/droplet exposure is known or suspected in an individual exhibiting miosis only or miosis and rhinorrhea only, it is recommended that the individual receive no antidote treatment but be closely observed for at least 18 h given that toxic effects of liquid percutaneous exposure may not manifest for several hours (Sidell, 1997 Cannard, 2006). Toxic effects from vapor-only exposure usually occur quickly (within minutes Sidell, 1997). Current... 

A single exposure to another nerve agent, cyclosarin, at concentrations that do not produce convulsions or severe clinical signs of toxicity can also produce performance deficits on learned behavioral tasks. However, with repeated exposure, the deficits are not persistent and recovery is complete. In addition, exposure concentrations not producing any evaluated clinical signs of toxicity, other than temporary miosis (in the case of inhalation exposure), do not produce performance deficits on the behavioral tasks (Genovese et al, 2006). 

SAFETY PROFILE Poison by ingestion, intravenous, and subcutaneous routes. Human systemic effects by ingestion and subcutaneous routes somnolence, miosis (pupillary constriction), and respiratory depression. An analgesic. Can cause drug dependency with repeated doses. When heated to decomposition it emits toxic fumes of NOx. See also CODEINE. 

SAFETY PROFILE Poison by ingestion and skin contact. Moderately toxic by inhalation. Human mutation data reported. Human systemic effects coma, lachrymation, miosis. A severe eye irritant. An insecticide. When heated to decomposition it emits very toxic fumes of NOx, POx, and SOx. 

SAFETY PROFILE A deadly human poison by skin contact and inhalation. (A small drop on the skin can kill a man.) A deadly experimental poison by ingestion, inhalation, skin contact, subcutaneous, intravenous, intramuscular, and intraperitoneal routes. Human systemic effects muscle weakness, bronchiolar constriction, nausea or vomiting, flaccid paralysis without anesthesia, miosis (pupOlar constriction), cholinesterase inhibition. A nerve gas used as a chemical warfare agent. To fight fire, use foam, CO2, drj chemical. When heated to decomposition or reacted with steam, it emits very toxic fumes of F and PO.. See also PARATHION. 

SAFETY PROFILE A poison by ingestion, inhalation, skin contact, intraperitoneal, subcutaneous, intramuscular, ocular, and intravenous routes. Moderately toxic by parenteral route. Human systemic effects by inhalation miosis (pupillary constriction) and headache. Experimental reproductive effects. Used as a basis for nerve gases. ... 

Systemic absorption of agents that inhibit the cholinesterase enzymes can result in miosis. Such substances are present in most insecticides and many toxic nerve gases. Toxic episodes involving the pupil have occurred in workers in fields being dusted with insecticides from an airplane. The miotic pupils of affected patients may not return to normal imtil 30 to 45 days after exposure to the toxic agent. 

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