Paracetamol poisoning 💊⚪🙊

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Paracetamol poisoning 💊⚪🙊 by Mind Map: Paracetamol poisoning 💊⚪🙊

1. Uses in therapeutic dose :😃

1.1. Non-narcotic analgesic

1.2. Anti-pyretic

1.3. Weak anti-inflammatory activity

1.4. Substitute for Aspirin in case of :

1.4.1. Peptic ulcer

1.4.2. Coagulation disorder

1.4.3. Viral infection to avoid risk of Reye's syndrome

2. Pharmacokinetics 🤔

2.1. Rabidly absorbed from small intestine

2.2. Peak plasma conc occur within :

2.2.1. 1-2 hrs ➡️ tab⚪ and capsule 💊

2.2.2. 30 mins ➡️ liq.preparations

2.2.3. 4 hrs ➡️ SR preparation

2.3. Peak plasma conc after therapeutic doses ➡️20 mg/L

2.4. About 20% plasma protein bound and may increase to 50% in case of overdose

2.5. Excretion: urine

2.6. Half life ➡️2 hrs but in liver dysfunction up to➡️ 17 hrs

3. Mechanism of APAP toxicity

3.1. -Metabolism: 52% sulfation ,42% glucuronidation ,2% excreted unchanged in urine ,4% biotransformed by CYP450 or CYP2E1….NAPQI .

3.2. -Sulfation, glucuronidation Are saturated & larger fraction of the drug is available for oxidation NAPQI…………. depletion of hepatic GSH stores ….. then covalently binds to hepatic, renal macromolecules ……cell death.

4. Phases of toxicity

4.1. Stage 1

4.1.1. Begins within (0.5-24) hrs and there is no specific symptoms (vomiting ,nausea ,anorexia , malaise ,diaphoresis)

4.2. Stage 2

4.2.1. Begins within (1-3 )days State of being well ( improve symptoms)- ⬆️ALT and ⬆️AST -PT may be prolonged -Right upper quadrant tenderness.

4.3. Stage 3

4.3.1. -within (3-5) days -Acute liver failure -Renal failure

4.4. Stage 4

4.4.1. -Within (5days -3 weeks). -Recovery stage . -the enzymes return to normal but hepatic necrosis persist.

5. Rumack-Matthew Nomogram

5.1. Relating Plasma or Serum acetaminophen concentration and probability of hepatotoxicity at varying intervals following ingestion of a single toxic dose of acetaminophen.

5.2. -If the level is above the normogram line, N-acetylcysteine should be commenced or continued. - N-acetylcysteine may be discontinued if levels fall below the normogram line.

6. Management of toxicity

6.1. 1-Gut decontamination :is most helpful if performed within (2hrs )of ingestion.

6.1.1. 1-Emesis: -Inducing vomiting with syrup of ipecac -has no role as ipecac induced vomiting delays the effective administration of activated charcoal and oral acetylcysteine.

6.1.2. 2-Gastric lavage: -It can be performed within 60 minutes of ingestion. - Done when amount ingested is potentially life-threatening.

6.1.3. 3-Activated charcoal: - It is the most common as reduces the absorption. -the most benefit within ( 30 min - 2 hrs ) -done later than 2 hours in patients with delayed gastric emptying.

6.2. 2-Hemodialysis and Hemoperfusion

6.2.1. -for rare situations: -early coma and metabolic acidosis are present prior to the onset of hepatic dysfunction and in the setting of a substantially elevated APAP concentration (over 1000 mg/L).

6.3. 3-Liver transplantation

6.3.1. In severe hepatotoxicity and potential to progress to hepatic failure. Putting in consideration: -Metabolic acidosis, unresponsive to resuscitation ,Renal failure, Coagulopathy and Encephalopathy.

6.4. Prevention

6.4.1. Paradote: (co-methiamol ) a combination tablet containing 100 mg methionine and 500 mg Paracetamol.

6.4.2. Methionine is considered as an alternative( antidote) for paracetamol.

7. Therapeutic Dose

7.1. - In adult,(Maximum daily 4g). - In Liver impairment (Maximum daily 1-2g). -In child, 75 mg/Kg/day.

8. Toxic dose

8.1. -In adult: 7.5-10 g - Children: 150 mg/kg

9. Acetyl cysteine

9.1. -NAC counteracts acetaminophen toxicity. - in cases more than 24 hours after ingestion. - oral and IV.

9.2. - oral Dose :Loading dose of 140 mg/kg. - 17 maintenance doses of 70 mg/kg given every 4 hours - Total treatment duration of 72 hours.

9.3. The IV formulation of NAC in these cases :Altered mental status ,GI bleeding and/or obstruction, A history of caustic ingestion ,in a pregnant woman and Inability to tolerate oral NAC .

9.4. Side effects: Anaphylactoid reactions