Salicylates drug interactions with

Many drugs interact with folate to affect its absorption, antagonize its biochemical activity, or increase its loss from the body. These drugs include ethanol, phenytoin, and oral contraceptives. Salicylates can compete with foUc acid for plasma protein binding. Methotrexate, a cytotoxic agent, is a folate antagonist that inhibits the biosynthesis of this coenzyme. 

Drugs that may interact with carbonic anhydrase inhibitors include cyclosporine, primidone, salicylates, and diflunisal. 

Although acid-base and electrolyte disturbances were not reported in the clinical trials, these disturbances have been reported with oral CA inhibitors and have, in some instances, resulted in drug interactions (eg, toxicity associated with high-dose salicylate therapy). 

The acidic NSAIDs include the salicylates and an increasing number of other compounds. The latter agents, as a group, share many common properties they may have toxicities, are highly protein bound and have the potential for interacting with other protein-bound drugs. The choice of a particular agent often depends on the reaction of the patient. Table 36.3 illustrates pharmacokinetic properties of selected NSAIDs. 

Azone (laurocapram) is used extensively as a transdermal permeation enhancer, and has also found use in buccal drug delivery. It is a lipophilic surfactant in nature (Figure 10.4). Permeation of salicylic acid was enhanced by the pre-application of an Azone emulsion in vivo in a keratinized hamster cheek pouch model [35]. Octreotide and some hydrophobic compounds absorption have also been improved by the use of Azone [36], Azone was shown to interact with the lipid domains and alter the molecular moment on the surface of the bilayers [37], In skin it has been proposed that Azone was able to form ion pairs with anionic drugs to promote their permeation [38],... 

Entrapment of drug substances in liposomes and micelles can lead to changes in their stability. When entrapment reduces the degradation rate, it can be used as a method for stabilizing pharmaceuticals. Aspirin can be partially stabilized by incorporation in L-a-dimyristoylphosphatidylcholine (DMPC)-based liposomes.489-491 Anesthetics such as procaine are also stabilized by incorporation in liposomes.490 Physostigmine salicylate in a phospholipid emulsion is stabilized through interaction with phospholipids at the oil-water interface and through incorporation into the internal phase of the emulsion (Fig. 131).549... 

Drug interactions mainly with first-generation drugs ->t hypoglycemia with cimetidine, insulin, salicylates, sulfonamides... 

Salicylates are highly bound to plasma protein albumin, with binding being concentration dependent. At low therapeutic concentrations of 100 pg/mL, approximately 90% of aspirin is plasma protein bound, whereas at higher concentrations of approximately 400 pg/mL, only 76% binding is observed. Plasma protein binding is a major factor in the drug interactions observed for salicylates. 

Interactions with the following drugs may increase the risk of hypoglycemia other hypoglycemics, sulfonamides, propranolol, salicylates, clofibrate, probenecid, pentamidine, valproic acid, dicumarol, cimetidine, MAO inhibitors, and alcohol. In addition, co-ingestion of alcohol may occasionally produce a disulfiram-like interaction (see p 186). 

Consider also azapropazone, phenylbutazone, and oxyphenbuta-zone , (p.498) and the salicylates , (p.502) for related drugs that do have adverse interactions with antidiabetics. 

Some lists, reviews and books on interactions say that chloramphenicol, aminosalieylie aeid, sodium salieylate, sulfamethoxypyridazine, tetracycline or tolbutamide interact with methotrexate, apparently based largely on the preliminary findings of a study in which male mice were treated for 5 days with each of 4 doses of methotrexate (1.53 to 12.25 mg/kg intravenously) and immediately afterwards with non-toxic intraperitoneal doses of the drugs listed. These drugs were said to decrease the lethal dose and/or decrease the survival time of the mice That is to say, the toxicity of the methotrexate was increased. The reasons are not understood, but it is suggested that displacement of the methotrexate from its plasma protein binding sites could result in a rise in the levels of unbound and active methotrexate, and in the case of sodium salicylate to a decrease in renal clearance. 

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