ASPIRIN AND SALICYLATE POISONING
OBJECTIVE 1: OUTLINE THE PHARMACOKINETICS OF ASPIRIN
ANSWER:
Pharmacokinetics in general describes the way that the body reacts to introduction of drugs, from absorption, to metabolism, to elimination from the body. It is a branch of pharmacology, the science of drugs. Although this concept is usually applied in external substances taken in by the body , pharmacokinetics also covers any chemical compound naturally existing in the body (hormones and secretions). Pharmacokinetics includes a description of how the substance entered the body, which for medicines, is the process of administering the drugs. There are several possible routes of entry, including intravenous (dextrose), oral (pills, capsule, syrup etc.), rectal (suppository), inhalational, etc. Pharmacokinetics also considers the metabolism of the substance in question. Metabolism refers to the process by which the substance is broken down into different component/s inside the body. The excretion of the substance is a process also shown by pharmacokinetics.
In 1899, Aspirin was introduced into the field of medicine in light of its numerous beneficial effects: it relieves pain, prevents inflammation, reduces fever, and helps minimize blocked artery. The usual way of ingesting aspirin is orally and is available as film-coated tablets, extended release tablets, or as a chewable tablet ( 2000). For children, aspirin may be administered as a suppository since they might find it difficult or uncomfortable to swallow aspirin pills. Upon reaching the gastrointestinal tract, it is generally absorbed fast and easily, although the PH level of gastric juice affects the speed of absorption. The dosage and intragastric concentration are also absorption rate factors.
In the initial pass, aspirin is hydrolyzed to salicylic acid in the liver. About 99 % of the ingested Aspirin is metabolized to Salicylate and other by-products. This is distributed to most tissues of the body. Aspirin have low plasma concentration, it doesn’t usually reach a plasma concentration level higher than 20 µg/ml if normal dosage was administered, and this may be attributed to the rapid hydrolysis ( 2005). This low range of bonding with plasma helps to achieve anti-inflammation feature of the drug and to keep the adverse effects to the minimum (1978). Salicylate starts to form in serum at about 5 to 30 minutes after oral administration. The Salicylate level reach its highest in a period of 2 hours in the case of uncoated aspirin, while for the extended release tablets (such as enteric-coated aspirin), it may take longer.
An important term that has a direct bearing on elimination from the body is biological “half-life”. In biology, half-life refers to the time it takes for the amount of a substance taken in by a living organism to decrease by 50 % by means of the organism’s metabolism and other biological process. If ingested in low dosage, the half-life of Salicylate is maintained at 2 to 3 hours, but at higher doses, saturation of the enzymes utilized in metabolism occurs and the half-life stretches to about 15 to 30 hours ( 2000). How are Salicylate and other components eliminated? The hydrolyzed salicylic acid joins with glycine and glucuronic acid, resulting in new byproducts: salicyluric acid and salicyl phenolic glucuronide, which facilitates excretion of Aspirin components through the urinary tract. The exact salicylate components in urine are summarized as follows: free salicylic acid -10%, salicyluric acid - 75%, salicylic phenolic - 10%, acyl - 5%, glucuronides and gentisic acid – less than 1% ( 2005).
OBJECTIVE 2: DISCUSS THE PATHOPHYSIOLOGY OF SALICYLATE POISONING
ANSWER:
Pathophysiology involves the changes in the normal functions and processes inside a body as a result of a disease or poisoning. The changes mentioned may include disturbance of the regular physical and biochemical processes of the body. In the case of poisoning, pathophysiology can be viewed as a reverse description of pharmacokinetics. The latter shows what the body does to a substance that gets in the body, the former describes what the substance does to the body.
The term “symptom” has a relation to pathophysiology since the former also refers to the detectable changes as direct results of a disease. Generally, the first symptoms exhibited by person suffering from Salicylate poisoning include nausea, vertigo, vomiting, fever, tinnitus, loss of hearing, agitation, and hyperventilation (1989). Salicylate toxicity affects numerous organ systems such as pulmonary, cardiovascular, hepatic, renal and metabolic system by means of opposing Krebs cycle enzymes, restricting amino acid synthesis, and uncoupling oxidative phosphorylation ( 2004). Krebs cycle and phosporylation are body processes involved in breaking down glucose. The fever is a result of the uncoupling of oxidative phosporylation ( 1985). Let us discuss the effects in specific system and organs.
According to (2004), Salicylate is considered a neurotoxin in large amount, and thus it attacks the Central Nervous System (CNS). In the said symptoms, tinnitus, loss of hearing, disorientation, and agitation are the manifestation of CNS problems. Hyperthermia (or simply fever) and comatose condition can also be expected as the central nervous system become susceptible to the toxicity (1998). Encephalopathy or syndromes that affect the brain causing confusion, lethargy, and seizures can also be attributed to salicylate intoxication ( 1991). In severe cases, fluid may accumulate in the brain causing swelling of the brain, also called cerebral edema (1985).
The respiratory system also gets stimulated by Salicylates in a variety of ways, and these respiratory problems are collectively known as ARDS or Acute Respiratory Distress Syndrome (1998). Hyperventilation, which causes the person affected to draw sharp quick breaths, are well associated with Salicylate poisoning. Another term used by doctors to describe the rapid breathing is hyperpnea. The rapid breathing cause increased gas exchange in the lungs leading to respiratory alkalosis, a condition where the blood or other body fluid gains high alkalinity. Therefore, respiratory alkalosis is a tell-tale sign of salicylate intoxication. The poisoned person could also acquire fluid accumulation in the lungs and difficulty of breathing. These characterize salicylate-induced pulmonary edema or SIPE (1998).
We can also expect Salicylate poisoning to cause disturbance in the gastric area because primarily, that is where the salicylates accumulate. Pylorospasm occurs after serum level goes high enough, making the patient vomit. Dehydration can be brought about by excessive vomiting. The patient may also suffer from reduction in motility (spontaneous movement) of the gastro-intestinal tract. Problems in the blood and circulation can also be encountered. Examples of this are hemorrhagic or bleeding problems and hemolysis or rapid destruction of red blood cells in the bloodstream (1986). The permeability of the capillary to protein can also be disrupted, thus high protein concentrations can be seen on the fluid in the lungs and in the urine ( 1989). There is also the possibility of bleeding in upper gastro-intestinal area (1998). The bleeding problems are related to the hemostatic defects. The hemostatic defect, as well as renal failure, was reportedly present in salicylate poisoning cases (1988). Renal failure occurs when the kidney is unable to excrete waste materials and maintain the balance of chemical composition in the body. The problem might arise from a defect in a kidney tubule.
Overall, the pathophysiology of Salicylate poisoning features several organ/system failures, and thus, experts observed that it shows a pseudo-sepsis syndrome. It is easy to mistake salicylate poisoning as a case of sepsis because of the similarity between the evident body reactions of the two. Specifically, the common points between the two are: fever, low failure of the lungs, failure of the kidney, shock, and death (1991).
OBJECTIVE 3: EXPLAIN THE CLINICAL INFORMATION AND LABORATORY INVESTIGATION OF THE PATIENT IN THE CASE STUDY
ANSWER:
Mr. was exhibiting the normal symptoms of Aspirin overdose toxicity. The buzzing in the ears (tinnitus) is one of the early manifestations of the poisoning ( 1989). The lethargy was a result of the deteriorating condition of the central nervous system ( 1984). The pain in the epigastric region (the upper portion of the abdominal area) was probably a result of reduced gastro-intestinal tract motility and the pylorospasm. The rapid heartbeat in relation to rapid breathing was expected due to several possible factors: 1. salicylate poisoning stimulates the respiratory center of the brain , 2. The oxidative phosporylation results in greater oxygen usage and thus greater demand for oxygen. The respiration problems and the fever are common complication of salicylate poisoning ( 1988). Let us discuss each laboratory investigation result one by one.
It is important that immediate test for Salicylate level be done as early as possible by means of the fluorescence polarization technique or spectrophotometrically (1991). Mr. plasma salicylate level is much higher as compared to the normal level of 150-300 mgl-1. That alone indicates that salicylate poisoning is the problem. Aside from that, another standard test procedure is to measure the partial pressure of Carbon Dioxide in the blood. The pressure is signified by the term PCO2. His PCO2 reading indicates a level lower than normal. The normal level is about 5.3 kPa. The reduction of Carbon Dioxide in the blood stream was a result of the rapid breathing and the increase in gas exchange. The low level of Mr. arterial PH reading was a result of respiratory alkalosis. It was also shown by studies that excessive salicylate displaces plasma bicarbonate and lower serum potassium concentration ( 2004). The results of measurement in plasma bicarbonate, plasma potassium and plasma sodium are therefore conclusive about Mr. Salicylate poisoning.
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