Hypoglycaemia can occur at therapeutic doses especially in those who develop renal impairment. In overdose these drugs cause a profound and prolonged hypoglycaemia, usually apparent within 8 hours post ingestion of a standard preparation. The sulfonylureas consist of glibenclamide, gliclazide, glimepiride and gliplizide.
They inhibit potassium efflux in the beta cells of the pancreas. As a result insulin is released resulting in a hyperinsulinaemic state.
- Well absorbed
- Peak levels at 4 – 8 hours
- Volumes of distribution are variable but small
- Elimination half life is also variable but prolonged in overdose
- Metabolised in the liver and renal excretion
- Hypoglycaemia (<4.0 mmol/L):
- Adult: 50ml bolus of 50% dextrose IV, repeat as required
- Children: 2 ml/kg of 10% dextrose IV, repeat as required
- Repeated hypoglycaemia: commence 10% glucose infusion, starting at 100ml and hour and monitor the blood glucose (children start maintenance fluids with o.9% saline and 5% dextrose +/- potassium). If further episodes of hypoglycaemia occur, treat with another bolus.
- Ultimately the dextrose is partly a temporising measure until octreotide can be given to halt the process
- Supplement potassium to a low-to-normal range.
- Ingestion of one tablet in the non-diabetic patient can cause a profound hypoglycaemia
- Onset of hypoglycaemia is usually within 8 hours (longer if extended release preparations, 18 hours and can be delayed up to 48 hours later)
- Hypoglycaemia is profound and prolonged (up to several days)
- Recent impairment of hepatic or renal function will predispose patients to hypoglycaemia even at therapeutic doses (the elderly are particularly vulnerable).
- Children: One tablet can cause fatal hypoglycaemia
- Hypoglycaemia, if present can be managed with dextrose.
- It is rare that higher doses of dextrose will be required once octreotide has commenced, however if greater than 100ml of 10% dextrose in adults or maintenance in paediatrics (0.9% saline + 5% dextrose solution) is required consider a central line to administer higher concentrations of dextrose.
- Screening: 12 lead ECG, BSL, Paracetamol level
- Regular blood glucose at least hourly until the patient is stable on octreotide
- EUC – monitor potassium and renal function
- 50 grams of charcoal to the co-operative patient who presents <1 hour with a standard preparation or <4 hours with a modified release preparation.
- Paediatric dose 1 g/kg
- Not clinically useful
- Do not start the antidote until a documented hypoglycaemia has occurred, equally giving boluses of dextrose without an episode of hypoglycaemia complicates the risk assessment.
- Once hypoglycaemia does occur may sure you have enough supply of octreotide
- All children require blood sugar level monitoring for 18 hours before medical clearance with advice to the parents.
- Adults require 8 hours of monitoring for standard preparations and 12 hours of monitoring for modified release. If asymptomatic and euglycaemic they can be medically cleared with advice (do not discharge at night)
- All symptomatic patients and those receiving treatment require admission and can be medically cleared once they can maintain euglycaemia on a normal diet for 12 hours post octreotide discontinuation.
- If hypoglycaemia occurred on therapeutic dosing they require management of any underlying disease and an endocrine review for ongoing therapy.
References and Additional Resources:
- Harrigan RA, Nathan MS & Beattie P. Oral agents for the treatment of type 2 diabetes mellitus: pharmacology, toxicity and treatment. Annals of Emergency Medicine 2001; 38:68-78
- Lung DD, Olson KR. Hypoglycaemia in paediatric sulfonylurea poisoning: an 8-year poison centre retrospective study. Paediatrics 2011; 127:e1558
- Murray L et al. Toxicology Handbook 3rd Edition. Elsevier Australia 2015. ISBN 9780729542241
- Spiller HA, Villalobos D, Krenzelok EP et al. Prospective multicenter study of sulfonylurea ingestion in children. Journal of Pediatrics 1997; 131:141-146.