Tox glipizide od pres
-
Upload
jeberhard -
Category
Health & Medicine
-
view
113 -
download
3
Transcript of Tox glipizide od pres
Current Topics in
Toxicology
ORAL HYPOGLYCEMIC OVERDOSE
Jessica Eberhard, Pharm D Candidate 2014
A 15yo female presents to the local hospital of a small remote town in Australia. Some 4 hours ago, following a family dispute, she intentionally ingested all of her father’s diabetic medications. A total of 75 X 5mg (375 mg) glipizide tablets and 29 X 500mg (14.5 g) metformin tablets are unable to be accounted for by her family. Using a risk assessment based approach, the management of sulphonylurea and metformin overdose is discussed.
TOXICOLOGY CASE
On arrival, the patient is vomiting, appears anxious 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: 14/15
PRESENTATION
GENERAL APPROACH TO ACUTE POISONINGS
Establish IV access
Bolus dose of 50 mL of 50% dextrose solution
RESUSCITATION 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 Factors
RISK ASSESSMENT
Oral hypoglycemic agent used extensively for treating Type-2 DM
Stimulates insulin release from pancreatic beta islet cells
Sustained & profound hypoglycemia is the primary concerning adverse effect of glipizide overdose Potential for delayed hypoglycemia by as much as 18 hours
especially in non-diabetic patients, children, & elderly
Prolonged monitoring of glucose levels is warranted
Seizures can be a presenting symptom in cases of unrecognized SU ingestion
SULFONYLUREAS (SU) - GLIPIZIDE
Action Is antihyperglycemic as opposed to hypoglycemic
Increases cellular insulin sensitivity
Does not cause significant hypoglycemic episodes, even in overdose
Lactic acidosis is the primary concerning adverse effect of metformin overdose Rare – no dose-response relationship exists
Monitor for signs and symptoms
Can be life-threatening if not recognized and treated early
BIGUANIDES - METFORMIN
Absorption of both glipizide & metformin is relatively complete within 1 hour
At 4 hours post-ingestion, gastrointestinal decontamination procedures would likely have minimal impact on subsequent clinical course and managementActivated Charcoal may be an option if ER formulation
DECONTAMINATION
Class Drug t ½ Renal Excretion
Hepatic Excretio
n
Main Adverse Effect
2nd-gen SU Glipizide 16-24 hr 3% 12% Hypo-glycemia (2-4%)
Biguanides
Metformin 1.3-4.5 hr 90% Negligible Lactic acidosis (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 at 100 mL/hr
Metformin overdose Usually causes few problems
Hemodialysis only in severe lactic acidosis to enhance elimination
ANTIDOTES
Attempts to maintain euglycemia by continued infusion of concentrated dextrose is problematic:
Administration of glucose stimulates further insulin release and rebound hypoglycemia
Requires careful monitoring in an intensive care setting
Requires a central line if >20% to avoid peripheral phlebitis caused by hypertonic dextrose solution
A 5-10% infusion is used to maintain euglycemia until octreolide can be sourced and administered
DEXTROSE IV INFUSION
Drug of choice in SU overdoses
A synthetic peptide analog of somatostatin
Binds to G protein-coupled somatostatin-2 receptors in pancreatic beta-cells, resulting in decreased calcium influx and inhibition of insulin secretion
Markedly inhibits insulin releaseIncreases serum glucose concentrationReduces dextrose requirementPrevents recurrent hypoglycemic episodes
OCTREOTIDE
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 infusion should be gradually tapered off
OCTREOTIDE
Bolus dose of 50 mL of 50% dextrose
IV infusion of 10% dextrose via peripheral cannula with careful monitoring & hourly bedside blood sugars Rural hospital did not stock octreotide
Royal Flying Doctor Service (RFDS) is enlisted to bring octreotide to the hospital, some 2 hours flying time away
While awaiting the RFDS arrival, the patient has another hypoglycemic episodeAn additional bolus dose of 50% dextrose is givenInfusion rate of 10% dextrose is increased
WHAT HAPPENED TO THE PATIENT?
On arrival of RFDS, a bolus dose of 50μg of octreotide
Flown to the nearest regional base hospital where an octreotide infusion at 25 μg/hr is started
Ongoing management for social & mental health issues
Patient is safely returned to her family & community a few days later
WHAT HAPPENED TO THE PATIENT?
Glatstein M, Scolnik D, Bentur Y. Octreotide for the treatment of sulfonylurea poisoning. Clin Toxicol (Phila) 2012; 50:795.
Soderstrom J, et al. Toxicology case of the month: oral hypoglycaemic overdose. Emerg Med J 2006;23:565-567.
Shannon MW, Borron SW, Burns MJ. Haddad and Winchester’s Clinical Management of Poisoning and Drug Overdose . 4 th ed. Philadelphia, PA: Saunders Elsevier; 2007: 1025-1030.
Szlatenyi CS, Capes KF, Wang RY. Delayed hypoglycemia in a child after ingestion of a single glipizide tablet. Ann Emerg Med 1998; 31:773.
REFERENCES