Rozel A.

Respuesto BS Pharmacy CASE 6 A 21 year-old woman was brought to the ER by her boyfriend, when he learned that she had ingested approximately thirty 325-mg Acetaminophen tablets in an attempted suicide. He was unaware of any previous significant medical or psychiatric illness; however, he reported that she had been seen in another ER several days earlier for persistent headaches. He said that she did not abuse alcohol or any other drugs. The patient was able to provide a history. She freely admitted to taking about 30 tablets approximately 3 hours before coming to the hospital. She stated that she could no longer stand to see her family being swallowed up by inflammation and that she wanted to kill herself. She said that shortly after taking the tablets, she developed a bad stomachache and felt extremely nauseated, vomiting once. She denied taking any other medications or alcohol in the suicide attempt. On physical exam, the woman was diaphoretic, pale and was suffering from abdominal distress. Vital signs: BP: 95/70 mmHg, temp: 37C, pulse: 100 bpm and resp: 20 breaths/min. Examination of the head, eyes, ears, nose and throat was unremarkable. The neck was supple, the lungs clear, and the cardiac examination was within normal limits. Examination of the abdomen revealed no masses or organomegaly. There was no guarding and only moderate midefrigastric tenderness. There was no peritoneal signs and the bowel sounds were normoavtive. Cranial nerves were grossly intact and reflexes were 2t bilaterally. She was oriented to time, place and person. The impression was acute overdose of acetaminophen in a suicide attempt. A 4hour serum Acetaminophen level was ordered to confirm the diagnosis and dictate management. Acetaminophen is one of the most common medications found in households. It is used for the treatment of pain and to lower fever. You should not take more than 4000 mg of acetaminophen a day. However too much of it, may cause toxic effect. Mainly causing liver injury, paracetamol toxicity is one of the most common causes of poisoning worldwide. Taking more, especially 7000 mg or more, can lead to a severe overdose if not treated. Properties

Physical Properties

Molecular Formula : C8H 9NO2 Molecular weight : 151.17 Chemical name : N-(4-hydroxyphenyl)acetamide properties : White crystal or Crystalline powder. Non smell. Taste is slightly bitter. melting point : 169-172c log P : 0.51 ( Experimentally determined value ) 0.49 ( Calculated value ) Ionization Constant @pKa : 9.71 Solubility o aceton : easily soluble o ether,benzene : hardly soluble Saturated solution : slight acidity

Mechanism of Toxicity In cases of paracetamol overdose, the sulfate and glucuronide pathways become saturated, and more paracetamol is shunted to the cytochrome P450 system to produce NAPQI. As a result, hepatocellular supplies of glutathione become depleted, as the demand for glutathione is higher than its regeneration.[20] NAPQI therefore remains in its toxic form in the liver and reacts with cellular membrane molecules, resulting in widespread hepatocyte damage and death, leading to acute hepatic necrosis.[21] In animal studies, hepatic glutathione must be depleted to less than 70% of normal levels before hepatotoxicity occurs. Manifestation of Toxicity The signs and symptoms of paracetamol toxicity occur in three phases. The first phase begins within hours of overdose, and consists of nausea, vomiting, paleness, and sweating. However, patients often have no specific symptoms or only mild symptoms in the first 24 hours of poisoning. The second phase occurs between 24 and 72 hours following overdose and consists of signs of increasing liver damage. In general, damage occurs in hepatocytes as they metabolize the paracetamol. The individual may experience right-upper-quadrant pain.

The third phase follows at 3 to 5 days, and is marked by complications of massive hepatic necrosis leading to fulminant hepatic failure with complications of coagulation defects, hypoglycemia, kidney failure, hepatic encephalopathy, cerebral edema, sepsis, multiple organ failure, and death. Clinical Laboratory Analysis The most effective way to diagnose poisoning is by obtaining a blood paracetamol level. A drug nomogram called the Rumack-Matthew nomogram, estimates the risk of toxicity based on the serum concentration of paracetamol at a given number of hours after ingestion. To determine the risk of potential hepatotoxicity, the paracetamol level is traced along the nomogram. Use of a timed serum paracetamol level plotted on the nomogram appears to be the best marker indicating the potential for liver injury. A paracetamol level drawn in the first four hours after ingestion may underestimate the amount in the system because paracetamol may still be in the process of being absorbed from the gastrointestinal tract. Therefore a serum level taken before 4 hours is not recommended. Clinical or biochemical evidence of liver toxicity may develop in one to four days, although, in severe cases, it may be evident in 12 hours. Right-upperquadrant tenderness may be present and can aid in diagnosis. Laboratory studies may show evidence of hepatic necrosis with elevated AST, ALT, bilirubin, and prolonged coagulation times, particularly an elevated prothrombin time.[32] After paracetamol overdose, when AST and ALT exceed 1000 IU/L, paracetamol-induced hepatotoxicity can be diagnosed. [31] In some cases, the AST and ALT levels can exceed 10,000 IU/L. Management Emptying of the stomach: In the very few cases in which a person comes to the hospital minutes after taking the overdose, the doctor may attempt to empty the stomach. This can be accomplished by inducing vomiting or by placing a large tube through the person's mouth and into the stomach, putting fluid in and then pumping it out (gastric lavage). N-acetylcysteine (NAC): NAC is the antidote for toxic acetaminophen overdose. It is generally given by mouth. It works to reduce paracetamol toxicity by replenishing body stores of the antioxidant glutathione. Glutathione react with the toxic NAPQI metabolite so that it does not damage cells and can be safely excreted. The medication has a foul odor but may be mixed with juice or other flavorings to make it taste better. If the person cannot take NAC by mouth, a tube may be placed through the mouth and into the stomach to help administer it. If giving NAC by this method is not possible, the doctor may choose to give it by IV. NAC is generally given for 20-72 hours. Activated charcoal: Activated charcoal can be given by mouth to bind any drug remaining in the gastrointestinal tract.

Liver transplant: In patients who develop fulminant hepatic failure or who are otherwise expected to die from liver failure, the mainstay of management is liver transplantation. Liver transplants are performed in specialist centers.

Precaution and Prevention Always securely close acetaminophen containers and use child-proof bottles. Keep all medication out of the reach of children and securely locked up. Know the correct dose of acetaminophen and the amount of acetaminophen in the preparation being are used. If taken in recommended doses, there is no risk of poisoning from acetaminophen. Never mix different medications if both medications contain acetaminophen, except if instructed to do so by a doctor. For example, acetaminophen with codeineand cold medicine containing acetaminophen should not be taken together. Read product labels. They clearly indicate the contents. If you or a family member is depressed or suicidal, remove all medications and dangerous substances from the house and seek medical attention immediately. If a person is unsure about how and when to take pain medications, ask a doctor for a plan. Write this plan down and follow it. When a person is given a new medication, always make sure the doctor knows all of the medication and supplements that the person is taking, both prescribed and non-prescribed. The easiest way to do this is to keep a written list of medications and supplements and go over it with a doctor. Do not take acetaminophen if you consume more than three alcoholic beverages per day. Indeed, if you consume more than three alcoholic beverages per day, you should consult a physician before taking any pain medications and to discuss ways to reduce your alcohol consumption.