Inspired by Dr. Benjamin Bralove
Conference 2/3/2016
SULFONYLUREAS
CASE
- 52 yo M PMH type II DM BIBEMS after being found by wife unconscious.
- Initial FS 20. Given D50 in the field. Initial FS 20 in ED.
- Given additional amp D50 with improvement in MS but becomes obtunded 20 minutes later.
Mechanism of Toxicity
- Meds: Glyburide, glipizide, glimepiride
- Promotes pancreatic B-cell release of insulin through closing Katp channel/opening Ca channel → membrane depolarization → insulin vesicle exocytosis
Treatment
- Glucose
- Important to understand caloric equivalent of interventions
- Amp D50 = 100 calories = 1 oreo
- D5 1/2 NS @ 250 mL/hr = 50 calories/hour = 1 ritz cracker/hour
- Give D10
- Give starchy food if tolerating PO
- Important to understand caloric equivalent of interventions
- Octreotide
- Blocks voltage dependent Ca channel → prevents insulin release
- Prevents recurrent hypoglycemia
- Consider in patients with inadequate response to dextrose
PHENYTOIN
CASE
- 23 yo F with PMH HbSS, epilepsy p/w vertigo
- Difficulty ambulating over past 3 days, decreased visual acuity, dysarthria
- Patient in phenytoin and no history of overdose
Clinical presentation
- Symptoms dose dependent:
- Nystagmus (>15 mg/L)
- Ataxia (>30 mg/L)
- Lethargy (>50 mg/L)
- Mechanism of toxicity
- Inhibits post-synaptic Na channels → blocks burst of action potentials associated with seizures
- Cerebellum and hippocampus exhibit physiologic spontaneous neuronal burst activity
- Class 1b antiarrhythmic agent
- Case reports of bradydysrhythmias in patients taking medications that raise phenytoin levels
- Diluent
- Propylene glycol depresses myocardial tissue and decreases PVR
- Hypotension, dysrhythmias correlate with dose and rate of administration
- Loading dose should be given on cardiac monitor
- Inhibits post-synaptic Na channels → blocks burst of action potentials associated with seizures
- Treatment
- Mainly supportive
- Activated charcoal may be useful if <24h post-ingestion
- HD ineffective due to heavy-protein binding of phenytoin
CLONIDINE
CASE
- 42 yo M found unconscious, bradypneic following argument with girlfriend
- Empty bottle of Clonidine found in room
- VS: HR 50, BP 80/60, RR 8, O2 96%
Bradycardia + Hypotension Tox Causes (ABCDS):
- A: Alpha-2 agonists, antiarrhythmics
- B: Beta-blockers
- C: Calcium channel blockers
- D: Digoxin
- S: Sedatives, severe opioid toxicity
Mechanism of Toxicity
- Direct acting α2-adrenergic agonist
- Acts centrally and peripherally
- Central: Stimulates central α2-adrenergic receptors → inhibits catecholamine release in periphery → sedation and reduction of BP and HR
- Peripheral: Stimulates peripheral α2-adrenergic receptors on vascular smooth muscle → vasoconstriction
- Abuse
- Possesses opioid agonist properties at the μ-receptor
- Provides similar “nod effect” as heroin
- Typical dose for abuse: 1-3 mg PO
- Usually only seen in heroin/methadone abusers
Treatment
- Supportive care
- Atropine
- IVF
- Theoretically, phenylephrine may be used if hypotension refractory to fluid resuscitation
- Ventilatory support as clinically warranted
- If severely hypertensive:
- May use nitro gtt
- Naloxone
- Some supporting evidence at case report and case series level
- May provide benefit if given early
- Minimal harm in opioid-naive patient
VALPROIC ACID
CASE
- 3 yo M BIB mom for lethargy
- Mom tried to wake him up this morning with difficulty
- No PMH; went to bed last night normal
- VSS, PERRL, skin exam normal, 2 mm sluggish pupils, diminished DTRs throughout, no e/o trauma
- Labs: Na 158, HCO3 7, Glucose 54, Ca 6.3, PO4 7.7, VPA level 801, AG 34
Mechanism of Toxicity
- Suppresses neuronal firing by blocking Na channels
- Increases GABA concentrations
- Metabolized by liver → elevations in LFTs and NH3 levels common
- Typically clinically insignificant at therapeutic VPA levels
- Class I antiarrhythmic; can affect QT
Clinical Features
- Lethargy/cerebral edema
- Acute pancreatitis
- Fanconi’s syndrome (pediatrics)
- Heart block
- AKI
- Alopecia
- Coagulopathy
- Pancytopenia
- Optic nerve atrophy
- ARDS
Laboratory Abnormalities
- AG metabolic acidosis
- Hypocalcemia
- Hyperammonemia (metabolized in the liver)
- Hypoglycemia (compounded with sodium salts)
- Hypoglycemia
- Hyper/Hypophosphatemia
Treatment
- Activated charcoal
- Hypotension
- IVF
- Pressors as necessary
- Consider HD
- Carnitine
- If associated hyperammonemia
- Hyperammonemia thought to be worsened in setting of carnitine depletion
- If associated hyperammonemia
- Naloxone
- Give if CNS and respiratory depression
- Minimal risk if patient not opiate dependent
REFERENCES
Chu, Jason. “Sulfonylurea agent poisoning.” Up To Date. http://www.uptodate.com, 03 Feb. 2016. Web. 12 Mar. 2016. http://www.uptodate.com/contents/sulfonylurea-agent-poisoning
Goldfrank, Lewis R. Goldfrank’s Toxicologic Emergencies. 9th Ed. New York: McGraw-Hill, 2011
Osterhoudt, Kevin. “Clonidine and related imidazoline poisoning.” Up To Date. http://www.uptodate.com, 29 Sep. 2014. Web. 12 Mar. 2016. http://www.uptodate.com/contents/clonidine-and-related-imidazoline-poisoning
Rivers, Colleen. “Valproic Acid Poisoning.” Up To Date. http://www.uptodate.com, 17 Apr. 2014. Web. 12 Mar. 2016. http://www.uptodate.com/contents/valproic-acid-poisoning
Su, Mark. “Phenytoin poisoning.” Up To Date. http://www.uptodate.com, 27 Oct. 2015. Web. 12 Mar. 2016. http://www.uptodate.com/contents/phenytoin-poisoning
Tintinalli, Judith E., and J. Stephan. Stapczynski. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide. 7th ed. New York: McGraw-Hill, 2011.