Sulfonylureas

• Sulfonylureas cause insuline release via cAMP/protein kinase C
• All sulfonylurea overdoses should be admitted for 24 hrs regardless of symptoms
• Antidote for recurrent hypoglycemia due to sulfonylureas (overdose or therapeutic misadventure) is octreotide, after your glucose
• Octreotide, a somatostatin analogue, turns of insulin secretion completely
• Octreotide 50 mcg SQ q 6 hrs for 24 hrs then observe for hypoglycemia 12-24 hrs

Fasono et al. Comparison of Octreotide and Standard Therapy Versus Standard Therapy Alone for the Treatment of Sulfonylurea-Induced Hypoglycemia. Ann Emerg Med 2007 Aug 29.

Carbamazepine

• Anticonvulsant that can be monitored (you can draw a level)
• Toxicity resembles a TCA with seizures and cardiac conduction delays
• > 40 mcg/mL assoc with coma, seizures, respiratory failure and cardiac toxicity
• Treat widened QRS comples with sodium bicarbonate
• Adsorbs very well to activated charcoal, multi-dose may be required

SSRI Toxicity

Things to watch for in patients that are taking SSRI:

• Therapeutic administration usually safe
• Hyponatremia is a common adverse effect (ADH secretion regulated by serotonin)
• Serotonin Syndrome is a possibilty in combination with other serotnergic drugs
• One SSRI is more problematic than the rest => Citalopram and Escitalopram
  • The only SSRI that can cause QT prolongation (even 24hrs after OD) and can cause seizures
  • This is the only SSRI with significant toxicity and unfortunately is the most commonly Rx by psych

GHB

• Sedating and amnestic, has become notorious in chemical submission (date rape)
• Very fast onset and rapid resolution though respiratory depression can occur 
• Difficult to test for with few labs and quickly eliminated through urine 
• Best chance to catch it is if the patient's first urine void is collected and tested

Valproic Acid (Depakote) - Increased use for both seizure disorder, migraine prophylaxis and bipolar disorder - Causes hyperammonemia with or without hepatic insufficiency (Liver enzymes could be normal!) - Hyperammonemia can occur at therapeutic concentrations and overdose - If the patient is sedated and has hyperammonemia, consider carnitine therapy antidotal - Carnitine IV or PO: 50-100 mg/kg bolus or divided bid, safe to give

Isopropanol (Commonly Rubbing Alcohol)

• Rubbing alcohol is 70% isopropanol, like drinking Bacardi 151 (151 proof)
• This is NOT a toxic alcohol in the traditional sense
• This causes a large ketosis, large osmol gap but NO anion gap and no acidosis
• This is because isopropanol is metabolized to acetone (a ketone) not an acid
• Toxicity: inebriation, hemorrhagic gastritis, sedation to the point of death/intubation

Ciguatera Poisoning - The most commonly reported cause of fishborne poisoning - Most commonly big-game fish: sea bass, grouper, red snapper, yellow-tail, kingfish and sturgeon - Ciguatoxin is bioaccumulated (thus big fish) and is heat and acid stable (unaffected by cooking) - Symptoms: 6-12 hrs post-ingestion GI, paresthesias, metallic taste, ataxia and paresis of legs are possible - The classic symptom is dysesthesias (sensory reversal where cold gives intense burning sensation) - Treatment: Supportive, consider mannitol, calcium, gabapentin - Avoid the following as it may exacerbate symptoms: opioids, barbiturates, steroids

Ethanol withdrawal can be measure objectively with the CIWA-Ar Scale. It is a prospectively validated tool to measure whether or not a patient is in ethanol withdrawal and can assist with management. Score Treatment <10 Does not require treatment 10-15 Treatment with either oral or intravenous benzodiazepines, outpatient > 15 Intravenous benzodiazepines with likely admission You must also take into account the patient's history, comorbidities and previous history of ethanol withdrawal/delirium tremens. ***The CIWA Score Sheet has been attached to this pearl***

Attachments

• 0709201013_ciwa-ar.pdf (10 Kb)

There are few medications/toxins that can cause clinically significant diabetes or hyperglycemia, here is the list: Vacor (PNU, an off the market rat poison) Streptozocin Alloxan Pentamidine Quinolones (gatifloxacin>moxifloxacin>ciprofloxacin) Olanzapine Antidote for Vacor, streptozocin, Alloxan: Niacinamide Antidote for Quinolones, Olanzapine: Remove agent, supportive care

Scombroid is one of the most common seafood poisonings. A classic EM board question. - Caused by ingestion of histamine in fish muscle - Naturally occurring histidine is converted to histamine by bacteria in unrefrigerated fish - Most common fish: tuna, mackerel, bonito, mahi mahi, blue fish and yellow tail - Symptoms: Within minutes to hours - flushing, urticaria, perioral burning, N/V/D - Treatment: Antihistamines, fluids, bronchodilators. Epinephrine and steroid for severe reactions.

- Classic Clinical Finding: Cyanosis out of proportion to clinical symptoms (look real blue but not SOB) - Causative Agents: Benzocaine (and other local anesthetics), dapsone, nitrites, phenazopyridine (Pyridium) - When do you treat: significant tissue hypoxia (MI, CVA, Dysrhythmias), and if MetHb >20% asymptomatic - Treatment: Methylene Blue 1-2 mg/kg (0.1 -0.2 mL/kg of 1% methylene blue) over minutes

- Few medications are uniformly lethal after a certain amount is ingested. - Colchicine is one of those medications, >0.8 mg/kg ingested=100%mortality regardless of treatment. - Many people prescribe it without knowing the adverse effect profile. - In fact, the prescribing instructions tell you to take the patient to toxicity (nausea and vomiting). - After an acute overdose this would be the sequence of events assuming surivival: Phase Signs & Symptoms i Nausea, vomiting, diarrhea, dehydration, leukocytosis (0-24hrs) II Sudden cardiac death (24-36hrs), pancytopenia, renal failure sepsis, ARDS, rhabdo (1-7d) III Alopecia, myopathy, neuropathy, myoneuropathy (>7d) - Colchicine prevents/destroys microtubule spindle formation and thus acts like a chemotherapeutic agent killing the cells that replicate most. - Think twice when prescribing this medication to someone, especially a patient at risk for suicide or medication noncompliance (where they think a little is good so more is better).

- Allergic reactions are extremely rare to local anesthetics but may occur with the "Amides". - If they occur, it is more likely due to a preservative found in some multi-dose vials: methylparaben. - Either switch to a single dose vial without preservative or change to an "Ester" where there is no cross-reactivity Amides: Bupivacaine, Etidocaine, Lidocaine, Mepivacaine, Prilocaine, Ropivacaine Esters: Chloroprocaine, cocaine, procaine, tetracaine

Here are some chest x-ray findings and cool toxins that can cause them (not an all-inclusive list): Diffuse airspace filling: salicylates, opioids, paraquat, phospgene, doxorubicin - Disease Process: Acute Lung Injury Focal airspace filling: hydrocarbons - Disease Process: Aspiration pneumonitis Pleural Effusion: Procainamide, hydralazine, INH, methyldopa - Disease Process: Drug-induced SLE Pneumothorax/Pneumomediastinum: "crack" cocaine and marijuana, IVDA into subclavian vein - Disease Process: Barotrauma Lymphadenopathy: Phenytoin, methotrexate - Disease Process: Pseudolymphoma Interstitial Patterns: Amiodarone - Disease Process: Phospholipidosis [Adapated from Goldfrank's Textbook of Toxicologic Emergencies, 8th Edition, Table 6-3, p. 74]

Opioids Opioids in general cause respiratory depression, miotic pupils and some mild hypotensions and bradycardia when the patient is comatose. All opioids can cause varying degrees of histamine release. However, not all opioids are similiar, here are the unique toxicities of some various opioids - keep them in mind when you prescribe them: 1) Propoxyphene - seizures and TCA like effects, also not very effect analgesic 2) Meperidine - seizures, serotonergic (thus increased abuse potential) 3) Methadone - long half-life (30+hrs) and QT prolongation 4) Hydromorphone - rare seizures and most common opioid that causes iatrogenic overdose because of its potency. (Easy to write 2 mg of "Dilaudid" but that is equivalent to 14 mg of morphine!) 5) Tramadol - seizure (common) and serotonergic, this is only 20% opioid 6) Fentanyl - rigid chest syndrome with rapid IV administration causes intercostal muscle contraction - not good

Chemical Weapons of Mass Destruction There are a variety of chemicals utilized as WMD and can be categorized as: nerve agent, blistering agent or incapacitating agent: Nerve Agents: (Sarin, VX) cause a parasympathetic toxidrome due to inhibition of Acetylcholinesterase. Antidote is pralidoxime, benzodiazepines and atropine. Blistering Agents: (Mustard Gas) Must be treated like a severe burn patient causing extreme pain and sloughing of the skin. Incapacitating Agents: (BZ) Causes anticholinergic toxidrome, your whole army starts to hallucinate and develop urinary retention. People armed, hallucinating and needing to pee makes for a highly ineffective military force.

Gastrointestinal Decontamination - Activated Charcoal Pharmacist P.f. Touery, in 1831, making a demonstration of the effectiveness of charcoal before the French academy of Medicine, survived after swallowing 15 g of strychnine (10x lethal dose) and an equal amount of charcoal - 3 tablespoons. (That's for you Dr. Rolnick) - Assess the patients' chance of becoming unresponsive or vomiting in relation to the ingestion if known. - Maximal benefit if given within 1 hour of ingestion, drug is likely still in the stomach. - No study has yet to show decrease in morbidity or mortality when empirically given to all ingestions. - Only one study has shown multi-dose activated charcoal to decrease morbidity and mortality and that was with a drug (oleander is like digoxin) that is enterohepatically metabolized. de Silva HA, et al. Multiple-dose activated charcoal for treatment of yellow oleander poisoning: a single-blind, randomised, placebo-controlled trial. Lancet. 2003 Jun 7;361(9373):1935-8.

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.

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.

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