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Use and abuse of paracetamol type analgesics
Paracetamol is an analgesic that helps to reduce all types of pains such as;Muscle pains, headaches, arthritis, neuralgia, blows, pains in the oral cavity or pains that occur with the menstrual cycle. It is also antifebrile or antipyretic since it helps in reducing fever, flu or viral infections, this being responsible for the synthesis of prostaglandins from a polyinsaturated fatty acid (arachidonic acid) since it is part of the enzyme cox block COX(cyclooxygenase) in the central nervous system. “Paracetamol presents an inhibitory activity of the weak COX, and selective for the inhibition of COX in the brain and spinal cord, so it has no peripheral anti -inflammatory effects, it does not alter the platelet function, and instead it is active on perceptionof pain and about thermogenic mechanisms ”(Chandrasekharan, 2002)
There are three uses of this analgesic that are not very common or are in the process of acceptance, for example: a dose before sleep, a study about the quantity and quality of sleep with positive result showed that people woke up calmer and muchmore rested. Another article made in mice affirmed that the use of paracetamol in an epilepsy picture would decrease the serious seizures. A last job about this analgesic, but in the anomaly of the persistent arterious ductus he explained that small doses help the closing of this communication.
The analgesic is ingested orally, its filtration ends in the digestive tract, eliminating renally after 24 hours from its intake. In adults the dose is 4-5 daily and in children it depends on their weight. It has no anti -inflammatory effects, it does not cause any symptoms in the stomach, but excessive intake causes liver damage.
Paracetamol incites all the actions of the serotonergic pathIntestinal motility.
Paracetamol can interfere with analytical tests such as:
- Blood;since it increases transaminases, bilirubin, alkaline phosphatase, glucose, increased prothrombin and uric acid.
- Urine;Metadrenaline has been raised.
- Pancreatic function tests through bentiromide
- Determination of the main metabolite of serotonin.
- Knowing that this drug is metabolized at the liver level has a correlation with other medicines and other ways of relating in what we have:
- Oral anticoagulants;excessive dose of paracetamol causes the increase of it.
- Anticonvulsants;reduces the bioavailability of hepatotoxicity.
- Estrogens;influence the plasma levels of paracetamol.
- ASA diuretics;shorten the renal excretion of prostaglandins.
- Propanolol;Inhibits the entire enzymatic system of glucuronidation and oxidation of the analgesic.
- Probenecid;Minimum increase in therapeutic efficacy.
- Rifampicin;Increase in analgesic clearance due to the stimulus of his liver metabolism.
- Anticholinergic;reduces the time of gastric emptying, restricting its filtration.
- Ion exchange resins;adherence of the analgesic in the intestine.
- Zidovudina;Reduction of all the effects that the drug can present.
Hepatoxicity caused by this medicine has increased since most people who consume it are not based on an adequate dose, minimal poisoning in children can come from 150mg and in 10G adults, however, we must keep in mind other factors, since we are clear that this analgesic is synthesized in the liver in the vast major. Some of the factors included in Paracetamol poisoning are:
- Synthesis of cytochrome P450;This enzyme disables the drug either by excessive alcohol intake since this could be helpful in the face of damage or caused by other medications.
- Glutathione depletion: risks increase due to lack of food or acute alcoholism situations.
- Genetic factors: It is presented associated with Gilbert syndrome.
Every patient should be admitted to the intensive care unit in the face of liver confirmation, in order to remain carefully monitored, keeping under strict surveillance the evolution of liver and renal functions. (Muñoz-García, 2011)
"In the USA.UU. The start of the treatment with oral NAC at concentrations is recommended to 25% lower (150 mg/l at 4 h or 20 mg/l at 3 pm) ”(Farré, 2004) The treatment for poisoning will depend on thesituations and the total ingested, in cases that have been detected within the last hours of proceeding to consumption of vegetable carbon. "When the concentration of the drug in the blood is very high we can supply acteilcysteine orally or intravenously". (Saracco, -)
If known about poisoning during the first hours, very conventional gastrointestinal reparation measures can be taken:
- Gastric wash reducing 39% of the blood paracetamol.
- Vegetable activated carbon 52% decreases drug concentration. The use of this is applied every 4 hours, until the plasma is free of the medication.
- Acteilcysteine;Act by providing thiol groups or also called merchandise to resume with the toxic metabolite.
Some of the symptoms due to paracetamol overdose can be presented in 4 phases:
- Phase 1;issue of hours, the patient can vomit, but he has no more symptoms.
- Phase 2;(24 to 72 hours) more symptoms such as nausea, fatigue and ventral pain are presented, an exam is performed to see the plasma elevations in the liver.
- Phase 3: (72 to 96 hours) Nausea become chronic, they have blood losses and insufficient liver function, encephalopathy, coagulopathy, skin and eyes are yellow.
- Phase 4;(After 120 hours; death or replacement of the organs) The patient can be saved from the overdose of this drug or the liver failure and damage of other organs that can be lethal.
The risk of overdose lethality increases after 48 hours maximum 96 hours, after this time it decreases much, when some patients do not have improvements should opt for a liver transplant. This would be the correct way to help people with a totally damaged liver improving the quality of life. In order for a patient not to be suitable for a liver transplantation, it is due to different factors associated with the elderly (65 to 70 years onwards), terminal diseases such as cancer, heart failure and respiratory failure, infections that cannot be controlled and notPresent alcohol intake for approximately 180 days. Although certain points must be taken into account for a successful transplant;that present decrease in liver function, inconveniences of cirrhosis, ascites, hepatocarcinoma and liver encephalopathy. Most specialists as a psychiatrist, cardiologist, social workers, neurologists, etc., They will evaluate the patient to know if he is trained for surgery.
The differential diagnosis of the Paracetamol drug poisoning after the study of urine and plasma will present the following table:
- Viral hepatitis: produced by excess alcohol, chemical substances and drugs such as paracetamol.
- Porta vein thrombosis: It can be produced by liver cirrhosis due to excessive consumption of alcoholic beverages.
- Congestive hepatopathy: acute liver inflammation, caused by hepatotoxic medications.
- Budd – Chiari Syndrome: Liver vein thrombosis and can be presented with several symptoms such as jaundice, ascites, nausea, ventral pains, acute hepatomegaly.
- Alcoholic hepatitis: different types of alcohol’s great intake can be generated.
- Isoniazide poisoning: this could cause liver damage due to medication overdose with hepatoxicity.
- Reye Syndrome: causes liver inflammation in patients who are in a state of viral disease recovery such as flu and fever.
- Toxicity for other drugs or toxins.
Hepatic disease and paracetamol play an important role in the liver, this becomes a common problem because adult patients do not carry adequate control over the intake of this drug, adults and their excessive consumption of alcohol come to cause aof the greatest difficulties thus becoming liver -related chronic diseases, due to the hepatoxicity presented by this analgesic. The metabolic pathways of the paracetamol have not been affected until each of the different liver diseases are already highly developed. In liver cirrhosis they decrease only 4 grams, thus leaving a daily dose of 2 – 3 grams, a very different case occurs in patients with liver damage since they not only have active alcohol consumption, but also a malnutrition picturebeing likely that the metabolic pathway is already very defective, the dose for these patients cannot pass 2 grams daily.
The contraindications come through an investigation of the patient’s allergic history to the medicine. Women in a state of gestation should not consume this medication since it passes through the placenta and is hepatotoxic for the fetus, even so, paracetamol poisoning does not lead to a therapeutic abortion. Women giving to breastfeed can intake this drug without any complication, since it is recommended to consume to treat postpartum pain, without exceeding the daily dose as long as the doctor has prescribed it. “Although maximum concentrations have been measured in breast milk from 10 to 15 μg/ml (from 66.2 to 99.3 μmo/l) after 1 or 2 hours of ingestion, by the mother, of aSingle dose of 650 mg, in the urine of infants, paracetamol or their metabolites have not been detected. The half -life in breast milk is 1.35 to 3.5 hours ”(Valdecarrizo, 2017)
Paracetamol provides great pain relief in most people. The pain itself is not doing any damage, it is not something that can be cured and sometimes it makes no sense to make anything. We have to learn to handle pain ’(Dickson, 2015)
The 6 main causes caused by paracetamol abuse are:
- Liver problems;They present chronic hepatitis or death due to insufficiency.
- Gastrointestinal disorders;An acute pancreatitis and cholestasis can be formed due to the rapid inflammation of the gallbladder.
- Acute renal failure caused by high doses of paracetamol.
- Blood problems;They cause acute thrombocytopenia, reducing platelets in the blood.
- Side effects on the skin;from the meningococcus bacteria, leather spots and arterial hypertension.
- Respiratory disorders;as dyspnea or gravity eosinophilic pneumonia.
To conclude, the analgesic – antipyretic Paracetamol is one of the most recommended and managed medications for most viral symptoms and pains in general, this drug becomes one of the most effective and safe worldwide. It is in various presentations available and is one of the medications that does not need a medical prescription. Paracetamol itself does not have large side or irreversible effects if the appropriate dose is met, it has no serious problems in health or at the gastric level and much less at the renal level, it does not affect our plasma in any way. But if you have to keep in mind that people with liver damage or those who have great intake of alcoholic beverages can be more affected because of the hepatoxicity of this medication, all these patients must carry strict control by their respective doctor if they want to useof this drug to avoid mortal risks.