Paracetamol Poisoning

Toxic dose = 150mg/kg (75mg/kg if malnourished) or 12g in adults may be fatal (10-15g ~ 20-30 tablets)
Max. Therapeutic dose = 4g/day

Acute poisoning:
1 hr = larvage + activated Charcoal
4 hr = Paracetamol level
8 hr = N-acetylcysteine (within 8 hr, effectiveness is the same, afterwards it declines); alternative – Methionine
12 hrs = Review and repeat INR q12h
24 hr = review with results (see criteria for transfer)
48 h = review (if INR normal and pt stable, possible home)

N-acetylcysteine

  • to replenish hepatic glutathione

IVI regieme

1. 150mg/kg in 200mL of 5%DW x 15min
2. 50mg/kg in 500mL of 5%DW x 4 hr
3. 100mg/kg in 1L of 5%DW x 16 hr

 

Crieteria for transfer

  • Encephalopathy or increased ICP
  • INR >2.0 at <48 hr – or >3.5 at <72h (peak at 72-96h) N.B. LFTs are NOT good markers
  • Renal impairment ( Creat > 200), consider HD if >400) * monitor urine output and daily U&Es
  • Acidosis / Blood pH <7.3
    • Lactate > 3.5 mg/dL (0.39 mmol/L) 4 hrs after early fluid resuscitation
    • Lactate > 3 mg/dL (0.33 mmol/L) after full fluid resuscitation at 12 hours
  • Systolic BP < 80mmHg

 

King’s College Hospital Criteria for Liver transplantation

Paracetamol liver failure

  • Arterial pH <7.3 24 h after ingestion

Or all of the following:

  • PT > 100s
  • Creat > 300
  • Grade III or IV encephalopathy

Non-paracetamol liver failure

  • PT > 100s

Or 3 out of 5 of the following:

  1. Drug-induced liver failure
  2. Age <10 or >40y old
  3. >1wk from 1st Jaundice to encephalopathy
  4. PT > 50s
  5. Bilirubin > 300
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Compilation of Drugs involved in specific conditions (2)

Enzyme Inducers  (NO GAS in CaR)
  • NNRTIs – Nevirapine *
  • Omeprazole – Induces P-450 1A2 **
  • Griseofulvin, Glucocorticoids
  • Alcohol (chronic)
  • Sulphonyureas/ St John’s Wort
  • Carbamazepine,  Pheytoin, barbiturates, Primidone
  • Rifampicin, Quinine
*    NNRTIs either induce or inhibit depending on the concomitantly administered drug
**  competitive inhibitor of the enzymes CYP2C19 and CYP2C9
Enzyme Inhibitors  (DOG RAISE)
  • Diltiazem, Verapamil
  • Omeprazole, Cimetidine,
  • Gemfibrozil, Grapefruit juice
  • Ritonavir (PI in HAART)
  • Amiodarone/ Allopurinol/ Acute alcohol intake, metahnol(acute), Disulfiram;
  • Isoniazid, Imidazoles (ketoconazole, fluconazole)
  • Sulphonamides, Sodium valproate, SSRIs (fluoxetine, sertraline)
  • Erthyromycin, Ciprofloxacin, quinupristin, metronidazole, quinidine
  • * Drugs that cause displacement of warfarin from protein
NSAID, OHA, metronidazole, salicylates, Co-trimoxazole
Drugs which are known to cause impaired glucose tolerance include:

  • Thiazides, furosemide (less common)
  • Steroids
  • Tacrolimus, Ciclosporin
  • Interferon-alpha
  • Nicotinic acid
  • Atypical Antipsychotics e.g. Olanzapine
  • Beta-blockers cause a slight impairment of glucose tolerance.
They should also be used with caution in diabetics as they can interfere with the metabolic and autonomic responses to hypoglycaemia
Drug-induced thrombocytopenia (probable immune mediated)

  • quinine
  • abciximab
  • NSAIDS
  • diuretics: furosemide
  • antibiotics: penicillins, sulphonamides, rifampicin
  • anticonvulsants: carbamazepine, valproate
  • heparin
Drug causes of gingival hyperplasia

  • phenytoin
  • ciclosporin
  • calcium channel blockers (especially nifedipine)

Other causes of gingival hyperplasia include

acute myeloid leukaemia (myelomonocytic and monocytic types)
Drug-induced liver disease is generally divided into hepatocellular, cholestatic or mixed.
There is however considerable overlap, with some drugs causing a range of changes to the liver
The following drugs tend to cause a hepatocellular picture:

  • Paracetamol (Acetaminophen)
  • Diclofenac
  • Sodium Valproate, Phenytoin
  • MAOIs
  • Halothane
  • Anti-Tuberculosis: isoniazid, rifampicin, pyrazinamide
  • Statins
  • Alcohol
  • Ecstasy/ amphetamine
  • Amiodarone
  • Methotrexate
  • Methyldopa
The following drugs tend to cause cholestasis (+/- hepatitis):
  • Oral Contraceptive pill
  • Antibiotics: ciprofloxacin, flucloxacillin, co-amoxiclav, erythromycin*, nitrofurantoin
  • anabolic Steroids, testosterones
  • Phenothiazines: chlorpromazine, prochlorperazine
  • Sulphonylureas
  • Fibrates
  • rare reported causes: nifedipine
*risk may be reduced with erythromycin stearate
Drugs affected by acetylator status

  • isoniazid
  • procainamide
  • hydralazine
  • dapsone
  • sulfasalazine