UMEM Educational Pearls - Toxicology

One Pill Killers for Children Drug Class Mechanism of Action that Kills Sulfonylureas These hypoglycemic agents (ie. Glyburide) also have a long t Opioids Respiratory depression Imidazoline Clonidine and Oxymetazolone (nasal spray) cause bradycardia and respiratory depression Ca Channel Blockers Bradycardia & hypotension, especially diltiazem and verapamil Beta Blockers Extended release preparations are problematic There are some others but these are the most commonly prescribed pharmaceuticals. Remember, children under age 6 will not be able to swallow a pill and the pill itself is choking hazard. Proper poison prevention education for the parents is also needed.

Heavy Metal Poisoning Clues for Diagnosis Mees lines, indication of arrested nail growth, occurs in lead, arsenic and others Most heavy metals will cause a proteinuria Microcytic anemia and basophilic stippling seen in lead, arsenic, mercury Peripheral neuropathies in otherwise healthy person Thallium causes classic painful paresthesias in lower extremities

Urine Drug Screens Though we order them often, be sure you know what your results mean: Cannabinoids: an accurate test though clinically not important information, positive for 5 days to a full month with chronic users. Cocaine: the most accurate and precise test, positive for 3-5 days. Amphetamine: the most imprecise with many false positives and false negatives. Cough/cold preparations that contain pseudephedrine, phenylephrine or other decongestants can turn it falsely positive. BDZ: only benzodiazepines that are metabolized to oxazepam will turn positive. You can see false negatives with alprazolam and even lorazepam. Opioids: Semisynthetics like oxycodone and hydrocodone may give false negatives at low levels. This screen will NOT catch methadone, meperidine, fentanyl, propoxyphene, tramadol. PCP: False positives from dextromethorphan and ketamine

Tricyclic Antidepressants (TCA) - Lack of terminal 40msec R wave (R wave in AvR, S wave in I, AvL) means the patient is NOT TCA toxic. - 40msec R wave + QRS >100msec = possible TCA toxicity, treat with NaHCO3 and recheck ECG. - TCA toxicity defined by ECG; if QRS > 100msec, 33% seizures; if QRS > 160msec, 50% v tach Boehnert MT, Lovejoy FH Jr. Value of the QRS duration versus the serum drug level in predicting seizures and ventricular arrhythmias after an acute overdose of tricyclic antidepressants. N Engl J Med. 1985 Aug 22;313(8):474-9.

Digoxin Toxicity Most common finding on ECG when digoxin toxic: PVCs Most classic ECG in digoxin toxicity: PAT with block Pathognomonic finding (RARE): Bidirectional ventricular tachycardia Easy formula for administration of digoxin specific Fab (Digibind?? or DigiFab?). Remember to round up even if its 2.3 vials, give 3. [(Dig Serum Concentration(ng/mL)) x wt(kg)] / 100 = # vials

Lithium Toxicity Management Initial Therapy: 2x maintenance fluid with normal saline Hemodialysis is controversial but will remove lithium quickly Association of permanent neurologic sequelae with elevated lithium level(1) o Looks like a cerebellar stroke 1- Adityanjee. The syndrome of irreversible lithium-effectuated neurotoxicity (SILENT). Pharmacopsychiatry. 1989 Mar;22(2):81-3.

Hyperthermia Neuroleptic Malignant Syndrome (Dopamine Inhibition): treat with bromocriptine Serotonin Syndrome (5-HT1A agonism): treat with serotonin antagonist Malignant Hyperthermia (Genetic): treat with dantrolene

Diagnosing Salicylate Toxicity - Acute ingestion can initiially present with nausea, vomiting and a respiratory alkalosis - Toxicity defined by an anion gap metabolic acidosis with ketosis and normal glucose - Ferric chloride test (can get from chemistry set): couple of drops into urine, if it changes color to deep purple sensitive positive for presence of salicylate (sensitive but not specific)

Botulinum Toxin Most potent toxin on the planet where 7 picograms IV are lethal to a human Characterized by a descending flaccid paralysis w/o fever bulbar findings 1st Weapon of Mass Destruction but also seen in the IVDA Heroin population Black Tar Heroin outbreak with necrotic ulcers that produced C. botulinum o Most recently in Washington DC 2003 Centers for Disease Control and Prevention (CDC). Wound botulism among black tar heroin users--Washington, 2003. MMWR Morb Mortal Wkly Rep. 2003;52(37):885-6.

Acetaminophen Toxicity Hepatoxicity defined by AST >1000 King s College Criteria to prognosticate hepatic failure and need for transplant: o pH <7.3 o Creatinine >3.4 mg/dL o INR >6.5 o Hepatic encephalopathy Grade III or IV Low phosphate (<1.2 mmol/L) may be predictor of survival and elevated may be indicator of impending hepatic failure. (Especially 48 96 hrs post-ingestion) o Theory is phosphate used in regeneration/healing liver Gow PJ, Sood S, Angus PW. Serum phosphate as a predictor of outcome in acetaminophen-induced fulminant hepatic failure. Hepatology. 2003; 37(3):711.

Toxic Alcohols Unexplained anion gap metabolic acidosis => give fomepizole (antidote) Hypokalemia, hypocalcemia, elevated creatinine => think ethlylene glycol Visual disturbances => think methanol Ketosis without acidosis and high osmol gap => think isopropanol If osmol gap is >70; high specificity for a toxic alcohol ingestion

Hydrofluoric Acid (HF) Used in glass etching, brick/porcelain cleaning and available in hardware stores Death has been reported after JUST 2-3% body surface area exposure! Systemic toxicity: hypocalcemia, hyperkalemia and hypomagensemia Local effects: paucity of skin findings with tremendous pain Treatment: skin decontamination, correct electrolyte abnormalities and topical calcium gel for local pain Mayer TG, GrossPI. Fatal systemic fluoride due to hydrofluoric acid burns. Ann Emerg Med 1985; 14: 149-153.

Cyanide Presents with arterialization of venous blood (venous blood draw looks like ABG) Reason: o Hemoglobin is not able to offload oxygen o CN poisons cytochrome c oxidase preventing conversion of oxygen to water and thus production of ATP Old antidote: sodium thiosulfate New antidote: hydroxycobalamin binds CN producing cyanocobalamin (Vit B12) When you give it expects a dip in pulse because of its blue color. Remember CN will give you a beautiful 100% pulse all the way to death. Lee J, et al. Potential interference by hydroxocobalamin on cooximetry hemoglobin measurements during cyanide and smoke inhalation treatments. Ann Emerg Med. 2007 Jun;49(6):802-5. Epub 2007 Jan 8.

Hydrofluoric acid is a weak acid used primarily in industrial applications for glass etching and metal cleaning/plating. It is contained in home rust removers. Although technically a weak acid, it is very dangerous and burns can be subtle in appearance while having severe consequences.

Wilkes G. Hydrofluoric Acid Burns. Jan 28, 2010. 
http://emedicine.medscape.com/article/773304-overview

• 2 mechanisms that cause tissue damage*
  • corrosive burn from the free hydrogen ions
  • chemical burn from tissue penetration of the fluoride ions
• Clinical features*
  • Cutaneous burns - absent findings to white-blue appearance
  • Pulmonary edema
  • Hypocalcemia, hyperkalemia, hypomagnesemia
• Treatment*
  • Decontaminate by irrigation with copious amounts of water.
  • With any evidence of hypocalcemia, immediately administer 10% calcium gluconate IV.
  • Cutaneous burns:
    • Apply 2.5% calcium gluconate gel to the affected area. If the proprietary gel is not available, constitute by dissolving 10% calcium gluconate solution in 3 times the volume of a water-soluble lubricant (eg, KY gel). For burns to the fingers, retain gel in a latex glove.
    • If pain persists for more than 30 minutes after application of calcium gluconate gel, further treatment is required. Subcutaneous infiltration of calcium gluconate is recommended at a dose of 0.5 mL of a 5% solution per square centimeter of surface burn extending 0.5 cm beyond the margin of involved tissue (10% calcium gluconate solution can be irritating to the tissue).
      • Do not use the chloride salt because it is an irritant and may cause tissue damage.

*Extracted from emedicine article.

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Methods: A large retrospective case series evaluated 121 children under 6 years old with hypoglycemia from a sulfonylurea ingestion.

Results:

• In addition to dextrose, patients who received octreotide had a median of zero hypoglycemic episodes after octreotide (compared to 2 before treatment, p < 0.0001).
• Median blood glucose concentrations after receiving octreotide were also higher (62 mg/dL vs 44, p < 0.001).
• Most required only 1 dose of octreotide with no reported adverse effects.

Authors' Conclusion: Octreotide administration decreases the number of hypoglycemic events and increases blood glucose concentrations in children with sulfonylurea ingestion.

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Valproic acid (VPA) is often used to treat seizure disorder and mania as a mood stabilizer. The mechanism of action involves enhancing GABA effect by preventing its degradation and slows the recovery from inactivation of neuronal Na⁺ channels (blockade effect).

VPA normally undergoes beta-oxidation (same as fatty acid metabolism) in the liver mitochondria, where VPA is transported into the mitochondria by carnitine shuttle pathway.

In setting of an overdose, carnitine is depleted and VPA undergoes omega-oxidation in the cytosol, resulting in a toxic metabolite.

Elevation NH₃ occurs as the toxic metabolite inhibits the carbomyl phosphate synthase I, preventing the incorporation of NH₃ into the urea cycle.

Signs and symptoms of acute toxicity include:

• GI: nausea/vomiting, hepatitis
• CNS: sedation, respiratory depression, ataxia, seizure and coma/encephalopathy (with serum concentration VPA: > 500 mg/mL)

Laboratory abnormalities

• Serum VPA level: signs of symptoms of toxicity does not correlate well with serum level.
• NH₃: elevated
• Liver function test: elevated AST/ALT
• Basic metabolic panel: hypernatremia, metabolic acidosis
• Complete blood count: pancytopenia

Treatment: L-carnitine

• Indication: hyperammonemia or hepatotoxicity
• Symptomatic patients: 100 mg/kg (max 6 gm) IV (over 30 min) followed by 15 mg/kg IV Q 4 hours until normalization of NH3 or improving LFT
• Asymptomatic patients: 100 mg/kg/day (max 3 mg) divided Q 6 hours.

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The pattern of prescription drug abuse continues to center around semisynthetic opioids like oxycodone and hydrocodone. Federal regulations have now raised hydrocodone to a schedule II drug like oxycodone. Despite efforts, the slope for natural and semisynthetic opioids remains steep.  The ED measures of education, limit prescriptions for acute pain, minimize number of days/pills prescribed and utlize the prescription drug monitoring program are some basics that can assist you in better prescribing habits.

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The pattern of prescription drug abuse continues to center around semisynthetic opioids like oxycodone and hydrocodone. Federal regulations have now raised hydrocodone to a schedule II drug like oxycodone. Despite efforts, the slope for natural and semisynthetic opioids remains steep.  The ED measures of education, limit prescriptions for acute pain, minimize number of days/pills prescribed and utlize the prescription drug monitoring program are some basics that can assist you in better prescribing habits.

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Question

A 3 year old is bitten by a spider on his right ear which is causing him intense pain, tachycardia, and muscle cramping. Identify the spider.  What is the treatment?

 

 

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