Additives toxic effects

To avoid all these problems we developed a method, described below, for internal irradiation of blood with short-lived Rn-222 decay products. These radionuclides are always present in the entire human body, according to the inhalation of the normal atmosphere. Therefore no substances are brought into the blood which could have additional toxic effects. Furthermore the concentration of these nuclides in the blood is always extremely small, because of their short half-life, so that any chemotoxic effect can be excluded. 

Additive toxic effects, 25 213—214 Adducts, of vinyl chloride, 25 632 Adenine, 8 174. See also ADP entries Adenocard, molecular formula and structure, 5 98t... 

Organometaiiic compounds (tributyitin, tetraethyi iead) Anti-fouiing paints, gasoiine additive Toxic effects inciuding birth defects, reproductive faiiure, cancer, and systemic poisoning. 

Corticosteroids [P] Increased salicylate elimination possible additive toxic effect on gastric mucosa. 

BETA-BLOCKERS NSAIDS - INDOMETACIN, PIROXICAM, POSSIBLY IBUPROFEN, NAPROXEN 1 hypotensive efficacy of beta-blockers. There does not seem to be this effect with other NSAIDs Additive toxic effects on kidney, and sodium and water, retention by NSAIDs. NSAIDs can raise BP by inhibiting renal synthesis of vasodilating prostaglandins. It is uncertain why this effect is specific to these NSAIDs Watch for 1 response to beta-blockers... 

LOOP DIURETICS CISPLATIN t risk of auditory toxic effects with cisplatin Loop diuretics cause tinnitus and deafness as side-effects. Additive toxic effects on auditory system likely Monitor hearing - test auditory function regularly, particularly if patients report symptoms such as tinnitus or impaired hearing... 

METHOTREXATE SULFAMETHOXAZOLE/ TRIMETHOPRIM t plasma concentrations of methotrexate and risk of toxic effects of methotrexate, e.g. myelosuppression, liver cirrhosis, pulmonary toxicity Sulfamethoxazole displaces methotrexate from plasma protein-binding sites and also 1 renal elimination of methotrexate. Trimethoprim inhibits dihydrofolate reductase, which leads to additive toxic effects of methotrexate Avoid concurrent use. If concurrent use is necessary, monitor clinically and biochemically for blood dyscrasias and liver, renal and pulmonary toxicity... 

COLISTIN PLATINUM COMPOUNDS t risk of additive renal and ototoxicity. The ototoxicity tends to occur when cisplatin is administered early during the course of aminoglycoside therapy Additive toxic effects Monitor renal function and hearing prior to and during therapy, and ensure the intake of at least 2 Lot fluid daily. Monitor serum potassium and magnesium and correct any deficiencies. Most side-effects of aminoglycosides are dose related, and it is necessary to t interval between doses and 1 dose of aminoglycoside if there is impaired renal function... 

VANCOMYCIN CICLOSPORIN Risk of renal toxicity and ototoxicity Additive toxic effects Monitor renal function closely... 

Fentanyl overdose leads to the classic triad of symptoms consistent with the opioid intoxication syndrome miosis, respiratory depression, and CNS depression. Additional toxic effects of fentanyl include bradycardia, hypotension, decreased gastrointestinal motility, euphoria, and acute lung injury. 

The toxic effects of some pesticide mixtures are additive, particularly when their toxic mechanisms are identical. The additive effects of the organophosphates chlorpyrifos and diazanon were demonstrated in one study. T Another study found the s-triazine herbicides atrazine and cyanazine to show additive toxic effects. Not all mixtures of similar pesticides produce additive effects, however. In one study, mixtures of five organophos-phate pesticides (chlorpyrifos, diazinon, dimethoate, acephate, and malathion) were shown to produce greater than additive effects when administered to laboratory animals. Another article discusses nonsimple additive effects of pyrethroid mixtures. Despite the similarities in their chemical structure, pyrethroids act on multiple sites, and mixtures of these produce different toxic effects. 10 ... 

Metal carbonyls, especially nickel carbonyl, Ni(CO)4, and iron pentacarbonyl, Fe(CO)5, are extremely hazardous species. They are volatile and readily taken into the body through the respiratory tract or through the skin. The carbonyls affect tissue directly and they break down to toxic carbon monoxide and products of metal, which have additional toxic effects. 

Sulfamethoxazole displaces methotrexate from plasma protein-binding sites and also i renal elimination of methotrexate. Trimethoprim inhibits dihydrofolate reductase, which leads to additive toxic effects of methotrexate... 

The manufacturers recommend that because bexarotene is related to vitamin A, any vitamin A supplements should be limited to 15 000 units or less daily to avoid potentially additive toxic effects. They also say that although no cases of hypoglycaemia have been seen, because of the known mode of action of bexarotene it should be used with caution if given with insulin or drugs that enhance insulin secretion (e.g. sulfonylure-as) or insulin sensitisers (e.g. thiazolidinediones). For a list of these drugs see Table 13.1 , (p.469). 

---