Intramuscular injections, toxicity

The relative toxicities of thallium compounds depend on their solubHities and valence states. Soluble univalent thallium compounds, eg, thaHous sulfate, acetate, and carbonate, are especiaHy toxic. They are rapidly and completely absorbed from the gastrointestinal tract, skin peritoneal cavity, and sites of subcutaneous and intramuscular injection. Tb allium is also rapidly absorbed from the mucous membranes of the respiratory tract, mouth, and lungs foHowing inhalation of soluble thallium salts. Insoluble compounds, eg, thaHous sulfide and iodide, are poorly absorbed by any route and are less toxic. 

The well-known adverse reaction formerly often observed after intramuscular injection of clemizol penicilUn in the treatment of syphilis with anaphylaxis-like symptoms plus CNS involvement in the absence of immimological sensitization to penicillin was called the Hoigne syndrome or embolic-toxic reaction, and might be explained by intravasal appUcation of LA with subsequent toxic effects [8]. 

Ethyl -fluorovalerate (IV) was found to be completely nontoxic, a subcutaneous injection of 160 mg./kg. failed to kill mice, and there was complete absence of any symptoms of poisoning. Intramuscular injection of 40 mg./kg. into rats similarly produced no toxic symptoms.1... 

Capreomycin has a pronounced suppressive effect against Mycobacterium tuberculosis and Mycobacterium bovis. Most strains of Mycobacterium kansasii are also sensitive to kanamycin, while other, nontuberculous strains are not sensitive to it. It is often used upon necessity of using parentemal therapy through deep intramuscular injections. Capreomycin is less toxic than kanamycin and has somewhat more of a bacteriostatic effect. Synonyms of this drug are capromycin, capastat, ogostal, and others. 

The emetines include emetine and dehydroemetine. These drugs act only against trophozoites. Their mechanism of action is based on eukaryote protein synthesis. They are parenterally administered because oral preparations are absorbed erratically and may induce severe vomiting. They are widely distributed and accumulate in liver, lungs and other tissues. The emetines are slowly elimination via the kidneys. Local side-effects in the area of the intramuscular injection are pain, tenderness and muscle weakness. Serious toxicity is common if the drugs are given for more than 10 days. Side effects include nausea, vomiting, diarrhoea but also cardiotoxicity. 

Alternative options are increasingly favoured in the form of oral iron polymaltose complexes. These are more expensive but attractive in that complications are less frequently encountered and the lethal toxicity that follows release of large amounts or ionic iron into the circulation does not occur. Carbonyl iron is not often used but available in some countries. In contrast combinations with vitamins and cobalt, still popular in certain areas, have no documented advantage and add quite unnecessary cost. Other routes are intramuscular injections and, except where oral administration is precluded, have disadvantages in that mobilization is unpredictable. Conversely, it is feasible to replace iron as a single total dose infusion but such procedures need to be given under supervised conditions. It is reiterated that the rate of rise in haemoglobin that follows adequate oral replacement is comparable to that achieved par-enterally. 

Calcitonin is also moderately effective in Paget s disease, but requires regular subcutaneous or intramuscular injection. Mithramycin has been used with some success, but is relatively toxic, and its use requires careful monitoring of blood counts to avoid marrow suppression, so it is rarely used in current practice. 

No persistent toxic signs were seen In dogs after Intramuscular injections at 1 mg/kg. Hematologic and biochemical values in the animals remained normal. 

Local irritation can produce severe pain after intramuscular injection and thrombophlebitis after intravenous injection. Renal toxicity, including interstitial nephritis and even tubular necrosis, has been demonstrated and has caused the withdrawal of cephaloridine from clinical use. 

Diepoxybutane is highly toxic to rats (oral LC50 78 mg/kg bw), mice and rabbits. Among surviving animals, there was eye, skin and respiratory tract damage. Intramuscular injection of rabbits with 25 mg/kg bw produced leukopenia and lymphopenia. However, once weekly gavage dosing of rats for one year with 5 mg D,L-diepoxybutane was not toxic (lARC, 1976). 

These compounds have high bioavailability after intramuscular administration and tend to concentrate in synovial membranes, liver, kidney, spleen, lymph nodes, and bone marrow. One month after an intramuscular injection, 75-80% of the drug is eliminated from the serum, but intramuscular gold s total body half-life is approximately 1 year. Auranofin is only about 25% bioavailable. Gold compounds are excreted approximately 66% in the urine and 33% via the feces. There has generally been no correlation found between serum gold concentration and either efficacy or toxicity. 

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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