Blood salicylate levels, increase

Garlic Allium sativum Lowers blood sugar, cholesterol, and lipids May cause abnormal blood glucose levels Increased risk of bleeding in patients taking the coumarins, salicylates, or antiplatelet drugs. 

Salicylate or aspirin overdose is characterized by tinnitus, confusion, rapid pulse rate, and increased respiration. The decreased partial pressure of arterial C02 (Pco2) plus increased fixed acids first cause alkalosis, which is followed by metabolic acidosis, dehydration, and loss of fixed bases. The picture may resemble diabetic acidosis, but the history of salicylate ingestion and blood salicylate levels above. 540 mg/100 mL clinch the diagnosis. 

Salicylic acid is a simple organic acid with a pKa of 3.0. Aspirin (acetylsalicylic acid ASA) has a pKa of 3.5 (see Table 1-3). The salicylates are rapidly absorbed from the stomach and upper small intestine yielding a peak plasma salicylate level within 1-2 hours. Aspirin is absorbed as such and is rapidly hydrolyzed (serum half-life 15 minutes) to acetic acid and salicylate by esterases in tissue and blood (Figure 36-3). Salicylate is nonlinearly bound to albumin. Alkalinization of the urine increases the rate of excretion of free salicylate and its water-soluble conjugates. 

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. 

There is an increased risk of toxicity of MTX when administered with the NSAIDs, salicylates, oral antidiabetic drugs, phenytoin, tetracycline, and probenecid. There is an additive bone marrow depressant effect when administered with other drug known to depress the bone marrow or with radiation therapy. There is an increased risk for nephrotoxicity when MTX is administered with other drug that cause nephrotoxicity. When penicillamine is administered with digoxin, decreased blood levels of digoxin may occur. There is a decreased absorption of penicillamine when the dmg is administered with food, iron preparations, and antacids. 

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. 

A newer therapeutic approach is the administration of betaine (6-12 g daily), which lowers homocysteine levels by favoring remethylation [33], A theoretical hazard of betaine treatment is increasing the blood methionine, sometimes to an extravagant degree ( 1 mmol/1). Experience to date indicates that betaine administration is safe, with no major side effects except for a fishy odor to the urine. Other therapeutic approaches have included the administration of salicylate to ameliorate the thromboembolic diathesis. Patients also have been treated with dietary supplements of L-cystine, since the block of the transsulfura-tion pathway in theory could diminish the synthesis of this amino acid. 

As salicylate enters the CNS, it stimulates the respiratory center to give further increased depth and also rate of respiration. This causes the blood level of carbon dioxide to fall, as there is greater alveolar permeability to carbon dioxide than oxygen. 

Salicylate also inhibits aminotransferases, leading to increased amino acid levels in blood and aminoaciduria. This also increases the solute load and contributes to the dehydration. 

A number of drugs are known to inhibit the renal secretion of certain other drugs, resulting in decreased clearance of the latter. Examples of drugs decreasing the renal clearance of other drugs include probenecid, salicylates, sulfinpyrazone, phenylbutazone, and thiazide diuretics. As mentioned previously, the inhibition of penicillin secretion by probenecid due to competition between the two for renal tubule carriers is used therapeutically to increase penicillin blood levels. 

Nausea, vomiting, tinnitus, and hyperventilation are seen early in toxicity. As severity of toxicity increases, intractable vomiting, hyperthermia, hypotension, tachycardia, confusion, coma, seizures, pulmonary edema, acute renal failure, and death may occur. Hyperglycemia may be seen early, whereas hypoglycemia may occur later in toxicity. Acid-base disturbances such as respiratory alkalosis and/or metabolic acidosis may be noted. Signs and symptoms of salicylate toxicity may be noted as blood levels rise over 30mgdN. ... 

Various studies show that salicylate derivatives act as much through direct local diffusion as through absorption by the dermal blood vessels and redistribution of salicylates in the whole body. The blood level of salicylates increases in direct proportion to the quantity applied, the resorption surface and the number of topical applications. A large amoimt of salicylates can be absorbed through the skin. 

Symptoms of salicylism can appear with chemical peels when large amounts of salicylate derivatives are applied on the skin, on large surface areas or repeatedly, causing a high blood level of saKcylates. In cases of toxic levels of salicylate in the blood, an increase in oxygen consumption causes hyperthermia by the uncoupling of oxidative phosphorylation. 

Salicylate, which is a degradation product of aspirin in the human, is lipid soluble and has a dissociable proton. In high concentrations, as in salicylate poisoning, salicylate is able to partially uncouple mitochondria. The decline of ATP concentration in the cell and consequent increase of AMP in the cytosol stimulates glycolysis. The overstimulation of the glycolytic pathway (see Chapter 22) results in increased levels of lactic acid in the blood and a metabolic acidosis. Fortunately, Dennis Veere did not develop this consequence of aspirin poisoning (see Chapter 4). 

One of the earlier studies demonstrating the role of blood flow on percutaneous absorption in humans used comparison dermal concentrations after topical application in vitro and in vivo (Schaefer and Stuttgen, 1978). Perfusion caused by cutaneous microcirculation also affected responses after the topical penetration of the vasodilator methyl nicotinate in humans (Guy et al., 1983). Altered transdermal drug absorption of the vasoactive nonsteroidal antiinflammatory drug (NSAID) methyl salicylate (MeSA) has also been attributed to changes in in vivo cutaneous perfusion. Exercise, heat exposure, or both increased MeSA absorption more than three times the control levels in six volunteers (Danon etal., 1986). A later case study reported that skin necrosis and other toxic symptoms occurred when a heating pad was used with a topical MeSA and menthol formulation meant to treat arthritic pain (Heng, 1987). 

---