Tag Archives: Pharmacology

Drugs That Affect the INR

Drugs that increase the INR and risk of bleed

Medications in italics are liver enzyme inhibitors and increase the INR. They act very quickly (can
be within 24 hours) and if the drug is withdrawn the effect disappears quickly depending on
the drug half-life. The INR should if possible be monitored within 72 hours of starting the
interacting drug and on withdrawal.

  • Gastrointestinal: cimetidine, omeprazole. and possibly other PPIs
  • Cardiovascular: amiodarone (liver enzyme inhibition is slow and may persist long after withdrawal requiring, weekly monitoring over 4 weeks), fibrates, ezetimibe, propafenone, propranolol
  • CNS: fluvoxamine, SNRIs, SSRIs*, tramadol
  • Antiinfectives: azole antifungals (esp. miconazole including oral gel and vaginal), co-trimazole*, macrolides* (can be serious but unpredictable), metronidazole, quinolones (can be serious but unpredictable), tetracyclines
  • Endocrine: anabolic steroids (and danazol), high dose corticosteroids, glucagon (high dose 50mg+ over 2 days), flutamide, levothyroxine
  • NSAIDs: Ibuprofen at lowest effective dose (+/-PPI) is probably safest if NSAID is required
  • Miscellaneous: alcohol (acute), allopurinol, benzbromarone, colchicine, disulfiram, fluorouracil, interferon paracetamol (prolonged use at high dose), sulfinpyrazone, tamoxifen, topical salicylates, zafirlukast
  • Herbal preparations/Food supplements: carnitine, chamomile, cranberry juice, curbicin, dong quai, fenugreek, fish oils, garlic, gingo biloba, glucosamine, grapefruit juice, lycium, mango, quilinggao

Drugs that decrease the INR

Medications in italics are liver enzyme inducers and decrease the INR. They act more slowly (up to
a week) with peak effect at 2-3 weeks and can persist for up to 4 weeks after stopping
depending on drug half-life. The INR will need checking after 1 week of concurrent therapy.

  • Miscellaneous: Alcohol (chronic), azathioprine, barbiturates, bosentan, carbamazepine,
    carbimazole, griseofulvin, mercaptopurine, nevirapine, OCP/HRT, propylthiouracil, raloxifene, rifampicin (most potent inducer), trazodone
  • Herbal preparations: avocado, co-enzyme Q10, green tea, natto, soya beans, St Johns wort (avoid)
  • Binding agents: cholestyramine, sucralfate,

Drugs that increase or decrease the INR

  • Miscellaneous: Ginseng, phenytoin, quinidine

Acetaminophen Overdose

Summary points

  • Patients still die from acetaminophen poisoning because they are not recognised to be at risk of harm or present too late for effective treatment

  • Patients who are malnourished, have been fasting, take enzyme inducing drugs, or regularly drink alcohol to excess are at higher risk of liver damage

  • Treat patients who have ingested too much acetaminophen within eight hours of ingestion whenever possible

  • If the time of ingestion is known, treatment can be based on blood tests taken after four hours

  • If the timing is uncertain or unknown, treatment should be started immediately in all patients who are at potential risk

  • Treat patients as high risk unless factors that increase risk of harm are known to be absent

 

Factors that increase the risk of liver injury after an overdose of paracetamol

  • High chance of glutathione depletion: Malnourished (for example, not eating because of dental pain or fasting for more than a day), eating disorders (anorexia or bulimia), failure to thrive or cystic fibrosis in children, AIDS, cachexia, alcoholism

    • Clinical clues: history, low body mass index, urinalysis positive for ketones, low serum urea concentration

  • Hepatic enzyme induction: Long term treatment with enzyme inducing drugs, such as carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, rifabutin, efavirenz, nevirapine, and St John’s wort. Regular consumption of ethanol in excess of recommended amounts.

    • Clinical clues: history, abnormal liver function tests, increased international normalised ratio, increased γ-glutamyl transpeptidase

  • Abnormal renal or hepatic function at presentation

 

Rumack-Matthew Nomogram

APAP

N-acetylcysteine Dosing

NAC doses

 

 

 

 

 

(note: this post contains images – it is best to view this post on the actual website).

BMJ 2011;342:d2218