Neuromuscular respiratory failure

A related organism, CL botulinum, produces a similar toxin which may contaminate food if the organism has grown in it and conditions are favourable for anaerobic growth. Meat pastes and pates are likely sources. This toxin interferes with acetylcholine release at cholinergic syrrapses and also acts at neuromuscular jimctions. Death fiom this toxin eventually results firm respiratory failure. 

Neuromuscular - mild stimulation to muscle paralysis, respiratory failure (curare), death Tobacco -South American -Strychnos family (curare) Blue green alga (anatonin A) Nicotine - blocks acetylcholine receptors Curare - used as a hunting poison, very potent receptor blocker... 

Application to the nerve cell ending would result only in topical anesthesia, and blockade of the neuromuscular junction could produce respiratory failure. Administration to the spinal cord is too general an answer. The injection must be near a nerve or nerve plexus proximal to the surgical site. 

Myasthenia gravis is an autoimmune disease resulting from production of autoantibodies against AChR at the motor end plate, causing defects in neuromuscular transmission. Depending on the muscles affected a patient may develop dysphagia or respiratory failure [1]. The appearance of pathological forms of erythrocytes such as stomatocytes, echinocytes etc., in peripheral blood causes microcirculation disorders [2]. 

The cause of death is usually respiratory failure due partly to neuromuscular paralysis, central depression, and bronchoconstriction. 

The effects of curare develop rapidly after it enters the body. Victims develop rapid weakness of voluntary muscles followed by paralysis, respiratory failure, and death. The cause is a blockade of nicotinic cholinergic receptors at the neuromuscular junctions in skeletal muscle. Unlike botulinum toxin, release of acetylcholine by the cholinergic nerve terminals is not affected. When curare is present, however, the acetylcholine that is released cannot bind to the receptors because they are reversibly occupied by the curare. As a consequence, nerve-muscle communication fails and paralysis ensues. 

Nicotinic symptoms may be observed initially, but muscarinic signs can be observed concurrently. Later in the course of poisoning, muscarinic signs predominate. Persistent depolarizing neuromuscular blockade may develop after initial resolution of the cholinergic crisis and can cause sudden respiratory failure and death (Reutter, 1999 Weinstein Alibek, 2003). Initial patient diagnoses and treatments are likely to be based on observations of signs and symptoms by the paramedic or other health care professionals at the scene (Table 25.3). Rescuers and health care workers must prevent direct... 

Excessive dosing with an anticholinesterase can actually worsen the muscle weakness in myasthenics if the accumulation of acetylcholine at the neuromuscular junction is sufficient to cause depolarising blockade cholinergic crisis). It is important to distinguish this type of muscle weakness from an exacerbation of the disease itself myasthenic crisis). The dilemma can be resolved with a test dose of edrophonium, which relieves a myasthenic crisis but worsens a cholinergic one. The latter may be severe enough to precipitate respiratory failure and should be attempted only with full resuscitation facilities, including mechanical ventilation, at hand. 

Low-spin rf transition metal complexes are classical examples of kinetically inert complexes. When injected into mice, species such as [ColNHsle] , [Fe(l,10-phen)3]2+, [Ru(bipy)3]2+, and [Os(terpy)s] rapidly cause convulsions, paralysis, and death by respiratory failure. They produce a curariform block at the neuromuscular junction, consistent with inhibition of acetylcholine esterase. The d isomers of [Rulphen)] " and [Os(phen)] + are 1.5-2 times more potent than the I isomers (9,10). These inert complexes are excreted largely unchanged from the body. 

In severe overdosage, CNS depression, circulatory collapse, and hypotension may occur. Coma and skeletal muscle paralysis may also occur followed by death due to respiratory failure. Acute overdosage with quaternary ammonium antimuscarinics may produce a curariform neuromuscular block and ganglionic blockade manifested as respiratory paralysis. 

Hansen-Flaschen, J. H., Bray insky, S., Basile, C. and Lanken, P. N. Use of sedating drugs and neuromuscular blocking agents in patients requiring mechanical ventilation for respiratory failure. A national survey. JAMA, 266, 2870-2875 (1991). 

According to the experimental data, a plasma concentration of 4 pg/ml is needed for oximes to counteract the toxic effects of nerve agents such as neuromuscular block, bradycardia, hypotension and respiratory failure (13). This concentration has been assumed since then to be the minimum concentration of any oximes (regardless of identity or molecular weight) required to counter nerve agent intoxication in man (14). If pralidoxime is administered at a dose of 10 mg/kg, it produced a plasma concentration of > 4 pg/ml in 5-10 min and maintained a concentration of >4 pg/ml for a further 50-55 min in humans (15). For the oxime HI-6, it was found that plasma concentrations of > 4 pg/ml were reached in 4-6 min for 250 or 500 mg of HI-6 and were maintained for 125 min (250 mg dose) or 200 min (500 mg dose) (16). Obidoxime has the similar profile. It produced a plasma concentration of > 4 pg/ml from 5 min to 2-3 h after administration at the dose of 5 mg/kg (17). The pharmacokinetics of HLq-7 is similar to the oxime HI-6. The data presented by Eyer and his co-workers showed that the mean absorp-... 

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