Salicylates Methotrexate

OAT2 SLC22A7 6p21 NM 006672, NM 153320 546/548 12 Liver Basal a-Ketoglutarate, salicylate, methotrexate, zidovudine, 5-fluorouracil, and so on... 

OAT2 (SLC22A7) Kidney, Basolateral PAH, salicylate, methotrexate. Probenecid,... 

Oral administration of bicarbonate may decrease the absorption of ketoconazole. Increased blood levels of quinidine, flecainide, or sympatiiomimetics may occur when these agents are administered with bicarbonate There is an increased risk of crystalluria when bicarbonate is administered with the fluoroquinolones. Fbssible decreased effects of lithium, methotrexate, chlorpropamide, salicylates, and tetracyclines may occur when these drag s are administered with sodium bicarbonate. Sodium bicarbonate is not administered within 2 hours of enteric-coated drugs the protective enteric coating may disintegrate before the drug reaches the intestine. 

Drugs that may interact include chlorpropamide, lithium, methotrexate, salicylates, tetracyclines, anorexiants, flecainide, mecamylamide, quinidine, and sympathomimetics. 

Drugs that may be affected by probenecid include acyclovir allopurinol barbiturates benzodiazepines clofibrate dapsone dyphylline methotrexate NSAIDs pantothenic acid penicillamine rifampin sulfonamides sulfonylureas zidovudine salicylates. 

Concomitant therapy - Aspirin, NSAIDs, and/or low-dose steroids may be continued, although the possibility of increased toxicity with concomitant use of NSAIDs, including salicylates, has not been fully explored. Steroids may be reduced gradually in patients who respond to methotrexate. Combined use of methotrexate with... 

Drugs that may affect methotrexate include oral aminoglycosides, charcoal, chloramphenicol, folic acid, NSAIDs, PCNs, probenecid, salicylates, sulfonamides, TCN, trimethoprim. 

Urine alkalinization is a treatment modality that increases elimination of poisons by the intravenous administration of sodium bicarbonate to produce urine with a pH of more than or equal to 7.5 and must be supported by high urine flow. This technique might be useful for the elimination of drugs with an acid pKa such as salicylates (but not recommended for phenobarbital intoxication for which multiple-dose activated charcoal is better), chlorpropamide, 2,4-dichlorophenoyacetic acid, diflunisal, fluoride, mecoprop, methotrexate. Complications include severe alkalemia, hypokalemia, hypocalcemia and coronary vasoconstriction. 

The present primary mode of therapy for these diseases involves the use 5-amino-salicylate (5-ASA) products. Often patients require additional medications, including corticosteroids, to help induce remission and various immune modulators, such as azathioprine, 6-mercaptopurine or methotrexate, to maintain remission. In Crohn s disease certain antibiotics, such as metronidazole and ciprofloxacin, and infliximab Remi-cade), an anti-tumor necrosis factor-a(TNFa) antibody, also have been used. The pharmacology of antibiotics, immunosuppressive drugs, and corticosteroids is discussed in Chapters 43,57, and 60, respectively. 

Salicylates, probenecid, and sulfonamides inhibit the renal tubular secretion of methotrexate and may displace it from plasma proteins. Asparaginase inhibits protein synthesis and may protect cells from methotrexate cytotoxicity by delaying progression from Gj-phase to S-phase. Methotrexate may either enhance or inhibit the action of fluorouracil, depending on its sequence of administration. 

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. 

Avoid alcohol, salicylates, and overexposure to sun or ultraviolet light during methotrexate therapy... 

Antimetabolites cause gastrointestinal toxicity including stomatitis and diarrhoea as well as bone marrow depression renal impairment potentiates the toxicity of methotrexate. Active excreHon of methotrexate by the renal tubule is blocked by salicylate, which also displaces it from plasma protein, increasing the risk of toxicity. Hepatic dysfunction potentiates the toxicity of 5-fluorouracil, since it is primarily metabolised by the liver. 

Methotrexate. Methotrexate is highly bound to plasma proteins, and agents such as the salicylates may be capable of displacing it from binding sites. Salicylates may also increase the action of methotrexate by inhibiting its renal excretion. The potential for toxicity with methotrexate dictates caution in all situations in which it is used. 

Methotrexate Salicylic acid Valproic acid Salicylic acid ... 

Concomitant use of heparin and oral anticoagulants can increase the risk for bleeding due to the antiplatelet effect of aspirin. In addition, use with alcohol can increase the risk of Gl bleeding. / spirin displaces a number of drugs (e.g., tolbutamide, nonsteroidal anti-inflammatory drugs [NSAIDs], methotrexate, phenytoin, and probenecid) from protein binding sites in the blood. Corticosteroid use can reduce serum salicylate levels by increasing the clearance of aspirin. 

Methotrexate + salicylates Potentiation of methotrexate toxicity Displacement of methotrexate from protein binding sites Owing to severity of methotrexate toxicity, salicylates should not be given to patients receiving methotrexate... 

Clinically important, potentially hazardous interactions with aspirin, boswellia, ciprofibrate, diuretics, methotrexate, NSAIDs, oxycodone hydrochloride, salicylates, tacrine, tacrolimus, urokinase... 

Clinically important, potentially hazardous interactions with cyclosporine, lithium, methotrexate, mifepristone, NSAIDs, quinolones, salicylates... 

Answer C. Ocular toxicity is characteristic of chloroquine and hydroxychloroquine. Corneal deposits are reversible, but retinal pigmentation can ultimately lead to blindness. Patients will complain about GI distress, visual dysfunction, ringing in the ears (note that tinnitus aiso occurs in salicylism), and itchy skin. Hydroxychloroquine also promotes oxidative stress that can lead to hemolysis in G6PD deficiency. DMARDs include gold salts (e.g., auranofin), methotrexate, and etanercept, but thioridazine is a phenothiazine used as an antipsychotic it lacks anti-inflammatory effect, but does cause retinal pigmentation. 

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