Current Topicsin ToxicologyORAL HYPOGLYCEMICOVERDOSEJessica Eberhard, Pharm D Candidate 2014
A 15yo female presents to the local hospital ofa small remote town in Australia. Some 4hours ago, following a family dispute, sheintentionally ingested all of her father’sdiabetic medications. A total of 75 X 5mg (375mg) glipizide tablets and 29 X 500mg (14.5 g)metformin tablets are unable to be accountedfor by her family. Using a risk assessmentbased approach, the management ofsulphonylurea and metformin overdose isdiscussed.TOXICOLOGY CASE
On arrival, the patient is vomiting, appearsanxious and slightly sweaty.BP: 110/75 mm HgPulse: 90 bpmRR: 18/minT: 36.8 C (98.24 F)BG: 3.0 mmol/L (54 mg/dL)Glasgow Coma Score: 14/15PRESENTATION
Establish IV accessBolus dose of 50 mL of50% dextrose solutionRESUSCITATION ANTIDOTES
“Hyperglycemia can kill you in 20 years…hypoglycemia can kill you TODAY.”- Dr. Dugan 5 Factors to consider:1. Agent(s)2. Dose(s)3. Time since ingestion4. Current clinical status5. Patient FactorsRISK ASSESSMENT
Oral hypoglycemic agent used extensively for treatingType-2 DM Stimulates insulin release from pancreatic beta isletcells Sustained & profound hypoglycemia is the primaryconcerning adverse effect of glipizide overdose Potential for delayed hypoglycemia by as much as 18 hoursespecially in non-diabetic patients, children, & elderly Prolonged monitoring of glucose levels is warranted Seizures can be a presenting symptom in cases of unrecognizedSU ingestionSULFONYLUREAS (SU) - GLIPIZIDE
Action Is antihyperglycemic as opposed tohypoglycemic Increases cellular insulin sensitivity Does not cause significant hypoglycemicepisodes, even in overdose Lactic acidosis is the primary concerning adverseeffect of metformin overdose Rare – no dose-response relationship exists Monitor for signs and symptoms Can be life-threatening if not recognized and treated earlyBIGUANIDES - METFORMIN
Absorption of both glipizide & metformin isrelatively complete within 1 hourAt 4 hours post-ingestion, gastrointestinaldecontamination procedures would likely haveminimal impact on subsequent clinical courseand managementActivated Charcoal may be an option if ERformulationDECONTAMINATION
Class Drug t ½ RenalExcretionHepaticExcretionMainAdverseEffect2nd-gen SU Glipizide 16-24 hr 3% 12% Hypo-glycemia (2-4%)Biguanides Metformin 1.3-4.5 hr 90% Negligible Lacticacidosis(rare)AGENTS
Sulfonylurea (glipizide) overdose Dextrose is given to rapidly restore euglycemia Octreotide is given as soon as possible after dextrose If octreotide is not available 10% dextrose IV infusion at100 mL/hr Metformin overdose Usually causes few problems Hemodialysis only in severe lactic acidosis to enhanceeliminationANTIDOTES
Attempts to maintain euglycemia by continuedinfusion of concentrated dextrose is problematic: Administration of glucose stimulates further insulinrelease and rebound hypoglycemia Requires careful monitoring in an intensive care setting Requires a central line if >20% to avoid peripheralphlebitis caused by hypertonic dextrose solution A 5-10% infusion is used to maintain euglycemiauntil octreolide can be sourced and administeredDEXTROSE IV INFUSION
Drug of choice in SU overdoses A synthetic peptide analog of somatostatin Binds to G protein-coupled somatostatin-2receptors in pancreatic beta-cells, resulting indecreased calcium influx and inhibition ofinsulin secretionMarkedly inhibits insulin releaseIncreases serum glucose concentrationReduces dextrose requirementPrevents recurrent hypoglycemic episodesOCTREOTIDE
In children, 1-1.5μg/kg SC or IV followed by (2-3) more doses 6 hours apart In adults, 50μg SC or IV followed by (3) 50μg doses every 6 hours During octreotide treatment, IV dextrose infusionshould be gradually tapered offOCTREOTIDE
Bolus dose of 50 mL of 50% dextroseIV infusion of 10% dextrose via peripheral cannula withcareful monitoring & hourly bedside blood sugars Rural hospital did not stock octreotideRoyal Flying Doctor Service (RFDS) is enlisted to bringoctreotide to the hospital, some 2 hours flying time awayWhile awaiting the RFDS arrival, the patient has anotherhypoglycemic episodeAn additional bolus dose of 50% dextrose is givenInfusion rate of 10% dextrose is increasedWHAT HAPPENED TO THE PATIENT?
On arrival of RFDS, a bolus dose of 50μg ofoctreotideFlown to the nearest regional base hospital where anoctreotide infusion at 25 μg/hr is startedOngoing management for social & mental healthissuesPatient is safely returned to her family & communitya few days laterWHAT HAPPENED TO THE PATIENT?
Glatstein M, Scolnik D, Bentur Y. Octreotide for the treatmentof sulfonylurea poisoning. Clin Toxicol (Phila) 2012; 50:795. Soderstrom J, et al. Toxicology case of the month: oralhypoglycaemic overdose. Emerg Med J 2006;23:565-567. Shannon MW, Borron SW, Burns MJ. Haddad and Winchester’sClinical Management of Poisoning and Drug Overdose. 4th ed.Philadelphia, PA: Saunders Elsevier; 2007: 1025-1030. Szlatenyi CS, Capes KF, Wang RY. Delayed hypoglycemia in achild after ingestion of a single glipizide tablet. Ann EmergMed 1998; 31:773.REFERENCES