Drug overdoses Flashcards
What dose is required of paracetamol to lead to toxicity?
At least 150 mg/kg can cause hepatic necrosis.
What is the maximum paracetamol overdose?
4g in 24 hours (usually 2 500mg tablets, 4 times a day)
What are the risk factors for paracetamol overdose? (x5)
- Chronic alcohol abusers
- Enzyme-inducing drugs which increase cytochrome P450 activity e.g., anticonvulsants and anti-TB drugs
- Malnourishment
- Anorexia nervosa
- HIV
What is the epidemiology of paracetamol overdose?
Most common intentional drug overdose in the UK.
What are the types of paracetamol overdose? (x3)
- ACUTE: excessive amounts ingested over less than an hour
- STAGGERED: excessive amounts ingested over more than an hour
- THERAPEUTIC EXCESS: without self-harm intent from paracetamol ingested at a dose greater than the licensed daily dose
What is the pathophysiology of paracetamol overdose?
- Paracetamol undergoes hepatic sulfation and glucuronidation. Resulting non-toxic metabolites are excreted in the liver.
- About 5% is metabolised by c-P450 to toxic N-acetyl-p-benzoquinone imine (NAPQI). This conjugated with glutathione to become non-toxic.
- However, in overdoses, a higher volume of paracetamol is metabolised by this toxic pathway and glutathione becomes saturated
- Excess NAPQI causes mitochondrial injury and acute liver necrosis which can lead to acute liver failure in severe cases. The enzymes that metabolise NAPQI are found in zone 3, hence hepatic injury is focussed here
- The presence of the same enzyme in the kidney may be a factor in variable degrees of renal injury occasionally seen following paracetamol overdose
What are the signs and symptoms of paracetamol overdose? (x4)
- 0-24 HOURS: asymptomatic, mild GI symptoms such as N&V, lethargy, malaise
- 24-72 HOURS: RUQ pain, vomiting, hepatomegaly
- OVER 72 HOURS: increasing confusion (encephalopathy), jaundice, coagulopathy, hypoglycaemia, renal angle pain (costovertebral angle)
- SEVERE may lead to initial presentation of coma and severe metabolic acidosis
What are the investigations for paracetamol overdose? (x3)
- Paracetamol levels: 4 hours post ingestion as this is when levels peak. Then assess need to treat based on normogram (see photo)
- LFTs: elevated ALT in acute liver injury
- ABG/VBG: may show lactic acidosis
What is the cause of lactic acidosis in paracetamol overdose? (x2)
- EARLY AFTER LARGE INGESTION: associated with coma
- LATER AFTER LIVER FAILURE DEVELOPMENT: predicts mortality
What is another name for paracetamol overdose?
Acetaminophen poisoning
What dose is required of aspirin to lead to toxicity?
Over 125 mg/kg of body weight.
What are the two types of aspirin overdose?
Acute and chronic (often in the context of renal insufficiency)
What is the pathophysiology of aspirin overdose?
- Aspirin (acetylsalicylate) is hydrolysed to salicylate in the GI tract, liver, and bloodstream
- Salicylate increases respiratory rate and depth by stimulating the CNS respiratory centre
- This hyperventilation produces respiratory alkalosis in the early phase
- Body compensates by increasing urinary bicarbonate and K+ excretion, causing dehydration and hypokalaemia
- Loss of bicarbonate together with the uncoupling of mitochondrial oxidative phosphorylation by salicylic acid, and build-up of lactic acid (due to salicylates effect on increasing metabolic rate) can lead to metabolic acidosis
- Salicylate also irritates the GI tract, interferes with haemostasis and leads to cerebral oedema
- Severe overdoses lead to CNS depression and respiratory failure
What questions should be asked when obtaining an aspirin overdose history? (x4)
How much? When? Any other drugs? Have you had any alcohol?
What are the signs and symptoms of aspirin overdose?
- EARLY: hyperpnoea, dizziness, fever, flushed appearance, tinnitus, deafness, epigastric pain, N&V
- LATE: lethargy, confusion, convulsions, drowsiness, respiratory depression, coma
