Salicylate Intoxication
INTRODUCTION
Acetylsalicylic acid (ASA) remains the analgesic most commonly used anti-inflammatory and antipyretic despite the emergence of new drugs being for this reason it is imposed as a model of intoxication in this chapter. In chronic use does not produce tolerance or addiction. It has analgesic, antipyretic, neurological, respiratory, on acid-base balance, cardiovascular, gastrointestinal, liver, kidney (uricosuric) on the blood and connective tissue metabolism and endocrine.
It features rapid oral absorption with peak plasma value after two hours of ingestion. , Is distributed to almost all body tissues, are excreted renally, depending on dose and urine pH (as salicylate free), finding favored by an alkaline pH.
The preparations most commonly used are sodium salicylate and aspirin. Others are salsalate, the salicylamide, diflunisal, methyl salicylate and salicylic acid.
Aspirin is a weak acid with a pKa 3.5, after absorption, is rapidly hydrolysed to give salicylic acid, which mostly is in ionized form (99%). The volume of distribution is low, 0.15 l / kg, and is not constant, it depends on the drug blood levels, the albumin and the presence of other drugs that bind to albumin, can increase its volume of distribution to more than 0.6 L / kg. Salicylates are extensively bound to albumin two receivers, one quickly becomes saturated and the other of lower affinity, is saturated with higher plasma concentration. Undergo biotransformation in the liver resulting in three main products: salicilúrico acid (glycine conjugate), phenolic glucuronide and acyl glucuronide excreted in this way along with a 10% free salicylic acid. Besides a small fraction is oxidized to gentisic acid, when combined with glycine, gentisúrico acid form.
It is eliminated primarily via renal excretion depending free salicylate dose and urinary pH and increasing the dose until they saturate metabolic pathways, so it moves from a kinetic of order 1 (elimination proportional to serum ) to a kinetic of order 0 (constant), an alkaline pH also favors the elimination, since it reduces passive reabsorption in distal tubule by increasing the ionized fraction of the metabolite and spread less. Therefore, the half-life varies between 2 and 40 hours with increasing doses of salicylate ingestion to acute overdose. Similarly, an increase of diuresis also increases the elimination, by increasing glomerular filtration.
Moreover, it is known to cross the placenta and enter breast milk, but slowly cross the blood brain barrier (BBB).
In both the fetus as in liver or kidney sick and elderly, are slowing their excretion decreased disposal or the immaturity of their metabolic systems.