Acetaminophen poisoning (Paracetamol overdose) : Medical summary for nerds
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| Emergency sign in a hospital |
1. What is paracetamol?
Paracetamol is a medication with chemical name para-hydroxyacetanilide (N-4- hydroxyphenylethanamide) commonly used as mild analgesic and antipyretic i.e., to control pain and reduce fever.
The common brand names include Tylenol and Panadol. The brand names in Nepal and India include Algina, Amol, Ampol, Anmol, Bisek, Cemol, Cetamol, Cetafast, Cetophen, Dolo, Dolopar, Evamol, Febrex, Femol, G-MOL, Hedex, Lotemp, Medomol, Monamol, Napa, Niko, Pacimol, Paracet, Paramol, Parapain, Phenocet, PICIMOL, Polar, Pyrinol, Rexamol, Supa, Supumol, Symol, Timol, Winmol, Panadol and hundreds of more.
Occasionally Paracetamol, acetaminophen is also abbreviated as PCM in Nepal and India.
2. How is paracetamol/acetaminophen given?
Paracetamol or Acetaminophen comes in multiple dosage forms including oral tablets, syrup and suspensions, oral drops, capsules, chewable tablets, suppositories and injectables like intramuscular IM injections and IV intravenous injection forms. This drug is also available in suppository form for per rectal route (PR).
3. How does Paracetamol work? Mechanism of action of Paracetamol (Mechanism of action of Acetaminophen)?
Paracetamol when taken by any route reaches blood and from there to hypothalamus which is part of brain.
This part of brain controls the temperature of the body and by manipulating the part, paracetamol controls fever.
The mechanism by which it controls pain is not clear yet.
4. What is the dose of Paracetamol / Acetaminophen? Can drug overdose occur with paracetamol?
The general recommended dose of paracetamol is 10-15 mg/kg per dose up to four times a day and for adults it can be given up to one gram per dose four times a day. At this dose it is useful for pain management as well as fever control. Maximum recommended dose is up to 4 grams i.e., 4000 mg per day under supervision of doctor to prevent toxicity and side effects.
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| molecular structure of paracetamol |
5. What are the dosage concentrations or tablets available for PCM/ Paracetamol?
Paracetamol is available in following dosage forms:
- Tablets and capsules: 250 mg, 500 mg, 325 mg and 650 mg
- Suppositories: 125 mg, 250 mg
- Syrup for children /pediatric: 125 mg/5ml, 250 mg/5ml, 500mg/5ml
- Drop for children/pediatric: 200mg/5ml, 400 mg/5ml
Various other concentrations are available in other parts of the world as well. The drug is also available in combination with various other group of drugs and medications like antihistamines, opioids (like tramadol+Paracetamol, codeine+paracetamol), cough medications, muscle relaxants and NSAIDS like ibuprofen (Flexon) etc.
6. Can paracetamol cause overdose?
Yes. Paracetamol can cause overdose and related side effects if given in dose recommended above. Hence, when you need to take high dose of paracetamol or repeated dose of paracetamol you should consider consulting a physician. Single very high dose for paracetamol can be very dangerous while repeated high doses can also lead to hepatic toxicity.
7. What happens when you overdose on paracetamol or acetaminophen? What are the symptoms of acute toxicity?
Overdose may occur if paracetamol is taken more than recommended dose by any route. The paracetamol poisoning (paracetamol toxicity or overdose) hits on liver mainly. It causes liver injury and finally liver damage and liver failure after high dose is taken. The liver may completely stop working also called fulminant liver failure. The patient may go into coma and subsequent multiorgan failure leading to death with few days.
The dose at which symptoms and signs of Paracetamol overdose occur in adults is 7.5-10g.
8. Will taking one or two extra tablets cause overdose? How many tablets of paracetamols can cause toxicity?
No. Generally, fulminant liver toxicity may not occur if you take one or two extra tablets. Generally, 8 tables of 500mg dose are safe in healthy adults.
9. What happens to the paracetamol or any drug that is in our body? Metabolism of Paracetamol/ Pharmacokinetics of Paracetamol?
Paracetamol is metabolized mainly in liver. It occurs in the microsomal enzyme system and by the reaction called conjugation. Thus-formed by products are excreted in urine.
10. How does paracetamol toxicity occur? What is pathophysiology of Paracetamol / PCM poisoning?
A single high dose or repeated dose making total large amount in a day or two may cause liver injury.
It is most common cause of acute liver failure in united states.
Dose and Chance of toxicity
- Single dose of 7.5-10 g
- Unlikely
- Single dose of 250mg/kg or more than12g/24hr
- Toxicity is likely to occur
- Dose of more than 350mg/kg
- All patient develop toxicity
- Mechanism of poisoning and toxicity is also explained in the image above.
NAC ( N-acetyl cysteine) is the antidote of paracetamol poisoning
11. Symptoms and signs of paracetamol toxicity, acetaminophen toxicity:
a. Asymptomatic
- No symptoms
b. Symptoms may appear up to only after 24-48 hours
Phases of toxicity:
- Phase 1:
- Up to 24 hours Anorexia or decreases appetite
- Nausea and vomiting Malaise
- Phase 2:
- Up to 72 hours
- Liver pain, right upper abdomen pain
- Anorexia
- Nausea and vomiting Low blood pressure and increased heart rate
- Phase 3: Hepatic phase
- 3 days to 4 days
- Nausea and vomiting continues
- Abdominal pain
- Lier starts to be destroyed and necrosis starts
- Jaundice
- Bleeding
- Hypoglycemia (fall in sugar levels)
- Death due to multiorgan failure
Phase 4: Recovery phase
- 4 days to 21 days
- Patient who recovered from phase 3 go into resolution of the symptoms
12. What investigations / tests are needed?
- Liver function tests (ALT, AST, ALP, Bilirubin, PT/INR)
- Glucose
- KFT/RFT
- Amylase and lipase (pancreatitis mcq here)
- hCG (for pregnancy)
- ABG
- Urine study
- ECG
- Chest X-ray
13. What is Rumack-Matthew nomogram?
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| activated charcol used for paracetamol poisoning |
14. How is paracetamol or acetaminophen overdose/toxicity treated?
b. Then if the patient has taken dose less than toxic, they can be discharged home but if they have taken more than toxic dose they should be treated with N-acetyl cysteine (NAC)
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| activated charcol in a container used for paracetamol poisoning |
- NAC given within 8 hours is 100% effective
- NAC ( N-acetyl cysteine) is the antidote of paracetamol poisoning
ii. IV formulation is generally preferred
iii. The oral dosage is as follows
a. Loading dose is 140 mg/kg
b. Total 17 doses of 70 mg/kg given every four hourly in total duration of 72 hours.
c. IV NAC is also preferred when orally not tolerated or contraindicated
iv. The IV dose is as follows
a. Loading dose: is given as 150 mg/kg; mixed in 200 mL of 5% dextrose solution(D5) and infused over 1 hour
b. Dose 2 is given 50 mg/kg in 500 mL D5 infused over 4 hours
c. Dose 3 is given 100 mg/kg in 1000 mL D5 over 16 hours
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| NAC ( N-acetyl cysteine) is the antidote of paracetamol poisoning |
15. Is liver transplant required for paracetamol poisoning?
If medical treatment for Paracetamol poisoning fails due to various reasons the liver completely stops working and never comes back also known as hepatic failure. Such patients if survived may need liver transplant.
16. What happens if I the patient comes late?
If the patient presents within 24 hours, then NAC still can be effective and should be started. The patient is further evaluated for potential toxicity of the acetaminophen and its effects as well. NAC also helps in liver repair in case of injures that have already occurred.
17. Which antiemetics can be given for nausea and vomiting?
Metoclopramide and Ondansetron are useful in this case. Metoclopramide is the drug of choice.
18. What is plasma acetaminophen level and whyis it required?
The doctor may require to check Plasma/blood level of paracetamol if the patient presents late and the amount of Paracetamol/acetaminophen ingested could not be told by the patient. This is useful to plan treatment accordingly.
Disclaimer: This information is for educationsl purpose only and is mainly for medical students with technical knoledge. If youre searching for medical advice please contact your doctor or nearby hospital. If anyone had taken more than recommended dose paaracetamol please take that person to hospital immidiately or contact your emergency health services immidiately.
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