Salicylate_Toxicity_Trina-Banerjee-MD-9-14-09 - Salicylate...

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Unformatted text preview: Salicylate Toxicity Salicylate Trina Banerjee, Renal Fellow Acid-Base Conference Pharmacokinitics and Mechanism of Action Mechanism Pharmacokinetics I Pharmacokinetics ASA and salicylic acid are absorbed within ASA 15-30 minutes 15-30 Salicylate is 90% bound to albumin An acidic pH promotes the movement of An salicylate into the tissues salicylate Pharmacokinetics II Pharmacokinetics After absorption ASA is de-acetylated Salicylate is either metabolized to gentisic acid or bound to glycine or glucuronide, or excreted as salicylate In tubular fluid, nonionized salicylate is In reabsorbed. Ionized salicylate cannot be reabsorbed reabsorbed Mechanism of Action Mechanism Inhibition of COX-1 and COX-2 Interference with oxidative phosphorylation Interference and the Krebs cycle and Activation of the CTZ on the Medulla Activation of the Respiratory Center in the Activation Medulla Medulla Clinical Manifestations Respiratory alkalosis Respiratory Increases tidal volume and respiratory rate Majority of the effect comes from the CNS Majority respiratory centers respiratory Peripheral chemoreceptors may contribute Metabolic Acidosis Metabolic Prevents the formation of ATP and promotes the Prevents formation of lactate and pyruvate formation Inhibits the Krebs cycle enzymes, encouraging lipid Inhibits metabolism and ketogenisis metabolism Inhibition of amino acid metabolism leads to amino Inhibition aciduria. aciduria. Hypoglycemia Hypoglycemia Salicylate causes secretion of insulin Salicylate can also decreased glucose levels Salicylate in the CNS despite normal serum glucose in Water and Electrolyte Losses Water Hyperthermia causing skin insensible losses Increased pulmonary insensible losses Vomiting Increased renal excretion of bicarbonate, Increased sodium and K+ follow. sodium Coagulation Abnormalities Coagulation Decrease in thromboxane A2 causes inablility Decrease to activate platelets to If ASA toxicity is severe the liver may not be If able to produce factors 2, 7, 9, and 10 able Predictors of Toxicity Predictors Based on Amount Ingested Based Requires the patient’s report of how much Requires was taken. It may be difficult to obtain this information, or it may be unreliable. information, Based on the Serum level Based Blood level of salicylate should be measured Blood for at least 6 hours after acute intoxication, or any time after chronic intoxication. Plasma levels should be checked every 2 Plasma hours until levels peak. Enteric coated tablets may take more than 24 hours to be absorbed. may Management Management Step 1: Decrease level Step Gastric lavage/activated charcoal Alkalinization of the plasma Alkalinization of the urine Dialysis Alkalinization Alkalinization Alkalinizing the serum ionizes the salicylate, Alkalinizing which keeps it from entering the tissues. Serum pH should be in the 7.5-7.6 range (no higher than 7.6) higher Alkalinizing the urine to pH=7.5 to 8 Alkalinizing Dialysis Dialysis Reasons to Perform It How to Do it Reasons Reasons Serum concentration >100mg/100ml CNS dysfunction CNS Renal failure Pulmonary Edema Severe acid/base electrolyte disturbances How To: How Molecular weight of ASA is 138 kDa Volume of distribution is 0.2L/kg Toxic levels are less protein bound Blood flow should be 350-400cc/hr for 3.5 to Blood 4 hours hours Step 2: Manage Complications Complications Correct hypokalemia Correct hypoglycemia Avoid intubation if possible ...
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This note was uploaded on 12/24/2011 for the course STEP 1 taught by Professor Dr.aslam during the Fall '11 term at Montgomery College.

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