Neuromuscular blocking agents toxicity

The cholinesterase inhibitors have important therapeutic and toxic effects at the skeletal muscle neuromuscular junction. Low (therapeutic) concentrations moderately prolong and intensify the actions of physiologically released acetylcholine. This increases the strength of contraction, especially in muscles weakened by curare-like neuromuscular blocking agents... 

Toxic effects, which depends on dose and duration of treatment, mainly manifest as ototoxicity. Aminoglycosides also may cause nephrotoxicity and are reversible if they are withdrawn. They are known to cause neuromuscular blockade hence, care is necessary when used along with neuromuscular-blocking agents. Other reactions include allergy and cross-reactivity infections, as well as... 

A variety of other tropane alkaloids have been isolated of which the most important is anatoxin-A, a highly toxic nACh-R agonist and depolarizing neuromuscular blocking agent deriving from Anabaena cyanobacterium species that can contaminate inland waters. 

DeIpNnIum barbeyi (larkspur) is a major cause of cattle loss. The toxic principle, a diter-pene alkaloid, is a neuromuscular blocking agent that acutely affects postsynaptic cholinergic and nicotinic receptors. Effects irKlude muscle tremors, excitemenL disorientation, bloat, arrhythmia, prostration, and death. 

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-... 

Emetine [EM e teen] and dehydroemetine [de hye dro EM e teen] are alternate agents for the treatment of amebiasis. They inhibit protein synthesis by blocking chain elongation1. Intramuscular injection is the preferred route. Emetine is concentrated in the liver where it persists for a month after a single dose. It is slowly metabolized and excreted and can accumulate. Its ty2 is 5 days. The use of these ipecac alkaloids is limited by their toxicities. Dehydroemetine is probably less toxic than emetine. Close clinical observation is necessary when these drugs are used. Among the untoward effects are pain at the site of injection, transient nausea, cardiotoxicity (e.g., arrhythmias, congestive heart failure), neuromuscular weakness, dizziness, and rashes. 

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