Muscular fasciculation

Persistent repetitive discharges lead to muscular fasciculations, acetylcholine depletion, and muscular weakness... 

After ingestion, gastrointestinal effects such as anorexia, nausea, vomiting, abdominal cramps, and diarrhea appear within 15 minutes to 2 hours. After skin absorption, localized sweating and muscular fasciculations in the immediate area occur usually within 15 minutes to 4 hours skin absorption is somewhat greater at higher ambient temperatures and is increased by the presence of derma titis. ... 

While normal cholinergic activity in the brain is essential for its normal functioning, strong activation of the cholinergic system in the CNS leads to loss of consciousness, to epilepsy-type convulsions, to muscular fasciculations (CNS-caused) and to down-regulation of the breathing center. 

Paralysis is preceded by muscular fasciculation, and this may be the cause of the muscle pain experienced commonly after its use. The pain may last 1-3 days and can be minimised by preceding the suxamethonium with a small dose of a competitive blocking agent. Suxamethonium is the neuromuscular blocker with the most rapid onset and the shortest duration of action. Tracheal intubation is possible in less than 60 seconds and total paralysis lasts up to 4 min with 50% recovery in about 10 min (t / for effect). It is particularly indicated for rapid sequence induction of anaesthesia in patients who are at risk of aspiration — the ability to secure the airway rapidly with a tracheal tube is of the utmost importance. If intubation proves impossible, recovery from suxamethonium and resumption of spontaneous respiration is relatively rapid. Unfortunately, if it is impossible to ventilate the paralysed patient s lungs, recovery may not be rapid enough to prevent the onset of hypoxia. 

Classic signs of acute toxicity include pinpoint pupils, muscular fasciculations, slow pulse, excessive salivation and lacrimation, and gastrointestinal symptoms (nausea, abdominal cramps, diarrhea, and loss of sphincter control). In severe cases, convulsions, coma, and heart block are common. Death is generally attributed to respiratory insufficiency caused by the combination of respiratory center depression, paralysis, and increased bronchial secretions. In children, the classic signs described previously may be infrequent, with the major symptoms being central nervous system depression, stupor, flaccidity, dyspnea, seizures, and coma. 

Almost all reports of human poisoning relate to the more potent type II pyrethroids, so it is not certain how well the two syndromes seen in animals applies to man, although what has been seen in man fits quite well with the animal observations. Human type II poisoning seems to be characterized by paresthesia (if via the dermal route), dizziness, nausea, listlessness, and muscular fasciculations. More severe poisoning caused epigastric pain, nausea and vomiting (if via the oral route), hypersalivation and pulmonary edema, opisthotonos, seizures, and coma. 

Stimulation of skeletal muscles by nerve agents will produce muscular fasciculation and twitching large amounts of the agent will cause fatigue and muscle weakness followed by muscular flaccidity. 

Toxic effects occur within seconds to 5 min of nerve agent vapor or aerosol inhalation. The muscarinic effects include ocular (miosis, conjunctival congestion, ciliary spasm, and nasal discharge), respiratory effects (bronchoconstriction and increased bronchial secretion), gastro-intestinal effects (anorexia, vomiting, abdominal cramps, and diarrhea), sweating, salivation, and cardiovascular (bradycardia and hypotension) effects. The nicotinic effects include muscular fasciculation and paralysis. The effects on the CNS can include ataxia, confusion, loss of reflexes, slurred speech, coma, and paralysis. 

VX, in amounts of 5-35 p.g kg-1 in small droplets, was applied to the volar aspect of the forearms of 103 subjects. The ambient temperature was 70-80°F (Ca 21-27°C) and the relative humidity ranged from 40% to 70% (Sim and Stubbs, 1960). Under these conditions, the amount estimated to produce a 50% inhibition of erythrocyte cholinesterase activity was 34 p.g kg-1. Symptoms, which usually occurred later than 6 h after exposure, included local sweating at the site (local muscular fasciculations were seen in only two subjects), a feeling of tiredness or weakness, nausea, vomiting and headaches. The incidence of vomiting was related to inhibition of cholinesterase after more than 70-80% inhibition of erythrocyte cholinesterase activity, more than half of the subjects vomited. There were few symptoms when cholinesterase activity was about 50% of normal, but symptoms increased in severity and duration as the enzyme activity fell below 30% of baseline activity. When VX was mixed with an amine (1 1), absorption of the agent was enhanced. 

It exerts a weak and feeble neuromuscular blocking activity which fails to produce signifieant muscle relaxation except imder deep ether anaesthesia. It has been found to potentiate the neuromuscular blockade caused by tubocurarine and to antagonize the action of decamethonium. Paradoxically, it has been used successfully to prolong and potentiate the relaxant effects of suxamethonium chloride. Besides, it has also been reported to decrease suxamethonium-induced muscular fasciculations. 

Diazinon, malathion, parathion, chlorpyrifos, dichlorvos irreversible inhibition of red blood cell cholinesterase, acetylcholinestera.se, plasma cholinesterase Mild fatigue, headache, blurred vision, diz/.ines.s, numbness of extremities, nausea, vomiting, excessive. sweating and salivation, tightness in chest Moderate weaknc.ss, difficulty talking, muscular fasciculations, miosis Severe unconsciousness, flaccid paralysis, moist rales, respiratory difficulty, cardiac arrhythmias, cyanosis... 

Acute inhalation toxicity is of a low order in animals. Subacute toxic effects in dogs exposed to 260-ppm vapors of hexachloroethane for 6 hours per day, 5 days a week for 6 weeks were tremors, ataxia, hypersalivation, head hobbling, and facial muscular fasciculations (Weeks 1979). 

The goals of therapy must be realistic. Current drugs will not immediately restore consciousness or respiration or completely reverse the skeletal muscle abnormalities, nor will intramuscular or intravenous drug therapy reverse miosis. Muscular fasciculations and small amounts of twitching may continue in a conscious patient long after adequate ventilation is restored and the patient is walking and talking. 

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