New version page

U of M PHAR 6124 - TREATMENT GUIDELINES FOR SALICYLATE POISONING

Upgrade to remove ads
Upgrade to remove ads
Unformatted text preview:

TREATMENT GUIDELINES FOR SALICYLATE POISONING(revised 2/03)Rick Kingston PharmDINCIDENCE AND SEVERITYOTC analgesic medications are the most commonly involved agents in accidental andintential drug overdoses.OTC Analgesic Exposures 64% acetaminophen19% ibuprofen17% aspirinOTC Analgesic Fatalities 62% aspirin34% acetaminophen04% ibuprofenAVAILABLE FORMSA. ANALGESICS•Aspirin (acetylsalicylic acid; ASA) is the most common agent associated withsalicylic acid poisoning.•Be aware that aspirin may still be found in a number of combination drugpreparations.B. TOPICAL PREPARATIONS•Methylsalicylate (Oil of Wintergreen; common ingredient in topical analgesicbalms such as Ben Gay (10-15%)) is the most dangerous salicylate formulation bystrength, but it is an infrequent cause of death.•One teaspoonful of Oil of Wintergreen contains 7000 mg salicylate which is alsoequivalent to 21 x 325 mg aspirin tablets.•Methylsalicylate is topically absorbed, therefore extensive percutaneousapplication may lead to toxic serum salicylate levels.C. BISMUTH SUBSALICYLATE (Pepto Bismol_)•1 ml of Pepto Bismol_ is equivalent to 8.77 mg of salicylic acid•60 ml of Pepto Bismol_ is equivalent to a therapeutic dose (650 mg) of aspirin.ESTIMATE OF ACUTE TOXICITYINGESTED DOSE (mg/kg)ESTIMATED TOXICITY< 150No toxic reaction expected150-300Mild to moderate toxic reaction300-500Serious toxic reaction> 500Potentially lethal toxic reactionAdapted from Ellenhorn:ESTIMATE OF CHRONIC TOXICITY•Risk for developing chronic salicylate toxicity is highly patient specific, althoughingestions exceeding 100 mg/kg/day for two or more days have been a consistantfinding in cases involving chronic salicylism.•Chronic salicylate poisoning is one of the most often misdiagnosed tox relateddisorders. This is especially true in cases involving elderly patients where an accuratemedication history or toxicology laboratory testing is not obtained. These patientsoften simply present with nausea/vomiting, confusion, and disorientation which laterprogress to mixed electrolyte, acid/base, and pulmonary disorders. One of the keyinitial indicators that should prompt the clinician to include salicylate intoxication onthe differential diagnosis is the presence of an unexplained anion gap.PHARMACOKINETICSA. ABSORPTION•Rapid absorption, therefore the rate limitng factor is the rate of dissolution.•The acid media of the stomach renders ASA poorly soluble. Precipitates maycoalesce to form concretions (bezoars) in cases involving large ingestions. Theseconcretions will delay absorption, and thus toxicity 8 to 24 hours!! Continuedabsorption from the concretion can occur for hours or days, essentiallymimicking a sustained release phenomena. It is imperative that the peak andsubsequent decline in salicylate concentrations be verified by obtainingserial salicylate levels.B. DISTRIBUTION1.) Concentration dependant protein binding (50 to 80% with therapeutic serumconcentrations)2.) Saturation of binding sites or a decrease in binding sites (e.g. cirrhosis,hypoalbuminemia, competitive drugs) produces greater tissue distribution offree salicylate and increased toxicity.3.) Peak concentration occurs 2 hours post-ingestion of therapeutic doses; peakconcentrations following an overdose is highly variable and patient dependent(see discussion under absorption).4.) Vd = 0.1 to 0.3 L/kg; dependent on protein binding and physiologic pH.Acidosis increases Vd because of enhanced tissue penetration by unionizedsalicylic acid in a more acidic environment.5.) The biologic half-life of Acetyl Salicylic Acid (ASA) is only 20 minutes sinceboth the stomach and blood rapidly hydrolyze ASA to the pharmacologicallyactive form, salicylic acid. The t1/2 of salicylic acid is normally about 2-4.5 hrsbut as long as 18-36 hours after overdose.C. ELIMINATIONFactors Affecting Salicylate elimination1.) Dose and urine pH: Salicylate elimination at therapeutic concentrations consists ofpredominantly of first-order hepatic elimination with only 10-20% of salicylateeliminated unchanged in the urine. In an overdose situation where metabolicpathways become saturated (zero order kinetic saturation), urinary excretion of freesalicylate becomes even more significant, accounting for 60-85% of total eliminationif an alkaline urine (pH>7.0) is established.“Ion Trapping” theory:•Salicylate is a weak acid (pKa 3.0). therefore an alkaline urine (pH > 7.0) favorsthe existence of ionized salicylate molecules in the urine. Both ionized andunionized salicylate molecules are filtered by the glomerulus, but only theunionized salicylate can be reabsorbed. By creating an alkaline environmentfavoring > 99% ionized salicylate molecules in the urine, the ionized salicylate inthe renal tubules may be “trapped” preventing salicylate reabsorption.“Diffusion Theory”** Some argue that limiting reabsorption of the ionizable fraction of filtered salicylatecannot be the primary mechanism responsible for enhanced elimination producedby sodium bicarbonate.•Since the quantitative difference between the percentage of molecules trapped inthe ionized between a pH of 5.0 (99% ionized) and a pH of 8.0 (99.999%) issmall, decreases in tubular reabsorption cannot fully explain the rapid increase inurinary elimination seen above a pH of 7.0.** Based on Fick’s Law of Diffusion: The rate of flow of a diffusing substance isproportional to its concentration gradient.•A concentration gradient between the unionized salicylate in the peritubular fluid(and blood) and the tubular luminal fluid is found in an alkaline urine. Since athigher urinary pH a greater proportion of secreted unionized molecules quicklybecome ionized upon entering the alkaline environment, more salicylate (ie,unionized salicylate) must pass the peritubular fluid into the urine in an attempt toreach equilibrium with the unionized fraction. Hence, predominantly increasedtubular secretion, not decreased tubular reabsorption may account for the increasein salicylate elimination observed in the alkaline urine.2.) Potassium•Increased potassium excretion as well as systemic acidosis in salicylate overdoseleads to hypokalemia.•Hypokalemia can make urinary alkalinization difficult to achieve, therebyreducing renal salicylate excretion. In the hypokalemic patient, the kidneys willpreferentially reabsorb potassium in exchange for hydrogen ions. Thus,replacement of potassium is essential.3.) Liver and Kidney


View Full Document
Download TREATMENT GUIDELINES FOR SALICYLATE POISONING
Our administrator received your request to download this document. We will send you the file to your email shortly.
Loading Unlocking...
Login

Join to view TREATMENT GUIDELINES FOR SALICYLATE POISONING and access 3M+ class-specific study document.

or
We will never post anything without your permission.
Don't have an account?
Sign Up

Join to view TREATMENT GUIDELINES FOR SALICYLATE POISONING 2 2 and access 3M+ class-specific study document.

or

By creating an account you agree to our Privacy Policy and Terms Of Use

Already a member?