UMEM Educational Pearls - Toxicology

Quinolone Induced Deliurim

Just to give you another reason NOT to give a quinolone - aside from the C. diff. This adverse effect occurs with quinolones unlike many other antibiotics. It can prolong hospital stay, cause falls and further medical work ups. Some risk factors are:

• Elderly
• Renal Insufficiency
• Benzodiazepine dependence (will actually precipitate withdrawal since quinolones displace the BDZ from the receptor - you have probably done this to a patient if you think about it, that may be why they went crazy)
• Epilepsy - can cause seizures especially with NSAIDs

As we are now into the winter months, exposures to ethylene glycol (antifreeze) and methanol (windshield washer fluid) increase.  Here is a good mnemonic for sorting through an anion gap metabolic acidosis:

C – cyanide, carbon monoxide
A – alcoholic ketoacidosis, acetaminophen (massive OD)
T – toluene (chronic from glue sniffing)
M – methanol, metformin
U – uremia
D – diabetic ketoacidosis
P – propofol infusion syndrome, propylene glycol, paraldehyde
I – iron, isoniazid, ibuprofen (massive OD)
L – lactic acidosis
E – ethylene glycol
S – salicylates, starvation ketoacidosis

SUCCIMER (DMSA)

• An oral agent used for the chelation of heavy metals, such as LEAD, ARSENIC and MERCURY
• Forms a water soluble agent that chelates the heavy metal, which are renally excreted
• Most common side effects are rashes, urticaria and GI
• A serious adverse effect is neutropenia, which is rare

A quick christmas one:

The Christmas Rose (Helleborus niger)

Actually containes cardioactive steroids - eating it will help your A fib with RVR as it will act like digoxin, as well as kill like it.

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Here is a table adapted from Goldfrank's Textbook of Toxicologic Emergencies 8th Edition - Drugs that May Induce Parkinsonism. MPTP is the story that everyone hears about and actually has links to Maryland. In 1976, Barry Kidston, a 23-year-old chemistry Maryland graduate student, synthesized MPPP (Meperidine or Demerol) incorrectly and injected the result. It was contaminated with MPTP, and within three days he began exhibiting symptoms of Parkinson's disease. Ooops - permanent.

Reversible

• Chemotherapeutics (several)
• Cyclosporine
• Calcium Channel Blockers
• Dopaminergic withdrawal
• Kava Kava (with manganese)
• Progesterone
• Sertraline
• Valproic Acid
• Trazodone

Irreversible

• Carbon Monoxide
• Cyanide
• Heroin
• Manganese
• MPTP

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NEW TREATMENT in diabetes

It was discovered that glucose given ORALLY caused more insulin release than glucose administered INTRAVENOUSLY. This led to the discovery of the incretin hormones, which are secreted by the gut (INtestinal SECRETion of INsulin), GIP and GLP-1.

The incretin-based therapies increase levels of GLP-1, either by providing an incretin mimetic (exenatide and liraglutide), or by inhibiting their breakdown by DPP-4 (sitagliptin, saxagliptin, vilagliptin)

Their administration results in:

• Stimulation of glucose dependent insulin secretion
• Suppression of glucagon secretion
• Slowing of gastric emptying
• Improvement if b-cell functioning

Causing:

• Improved glycemic control
• Decrease in A1C
• Mild weight loss
• Mild decrease in BP

                 STAY TUNED FOR DOSING AND ADVERSE EVENTS!

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The newest antidote for cyanide poisoning, hydroxocobalamin, has several advantages over the older Cyanide Antidote Kit (amyl nitrite, sodium nitrite, sodium thiosulfate).  Hydroxocobalamin works rapidly, does not induce methemoglobinemia, and does not cause vasodilation/hypotension.

• The first is self-limiting hypertension. However, think about the patient population you are treating.  They are most likely hypotensive from the cyanide/carbon monoxide poisoning.  Increased blood pressure is a welcome adverse effect in these cases.
• The second is red discoloration of the skin and urine, secondary to the red color of hydroxocobalamin (see attached picture).  This effect can be quite pronounced, especially if you aren’t prepared for it. There is no harm to the patient although it can last up to 8 days.

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 Toxicology Expert: Poisoning Of Harvard University Scientists "No Accident"

• 6 scientists in a Boston area lab drank coffee that was laced with sodium azide
• Presented with hypotension, nausea and vomiting - one had a syncopal episode
• Sodium Azide is a chemical compound (NaN3) that is used as a preservative at very low concentrations but in higher concentrations can be lethal. It is even found in the propellant that is found in automobile airbag mechanisms
• It acts similiar to cyanide where it inhibits cytochrome oxidase and presents like a cyanide poisoning.
• No antidote, cyanide antidote kit will not work

Zanamivir (Relenza) is another neuraminidase inhibitor effective against influenza strains A and B. We are currently reserving its use for patients with H1N1 that may develop resistance to oseltamivir (Tamiflu) since it has been effective in these situations with past influenza strains.

• Zanamivir is given by inhalation only (powder) and can therefore not be given to ventilated patients
• Treatment dose is 10 mg (two blister packs) BID for 5 days
• Prophylaxis is 10 mg (two blister packs) once daily for 10 days
• Most common adverse effects are respiratory related and include bronchospasm and cough
• Pregnancy category C (same as Tamiflu) and should be used in pregnant patients with suspected/confirmed H1N1 due to the increased risk of morbidity/mortality
  • In fact, zanamivir may be the preferable antiviral for pregnant women because of its limited systemic absorption

This is a semi-synthetic opiate with partial agonist activity at the mu receptor. For an example of what a partial agonist is - see attached illustration. It is used in opioid addiction but is not as regulated as methadone clinics. Take a small course and you are licensed to prescribed it.  Primary caregivers are now able to administer buprenorphine to assist addicts though it is not recommended if the patient is requiring more than 40mg of methadone (rules out everyone in Baltimore).

The tablets (Suboxone) also contain naloxone to prevent intravenous injection which would induce withdrawal. Naloxone is not orally bioavailable and thus can be mixed into the pill.

Overdose is treated like any other opioid and naloxone should work.

Buprenorphine can illicit an opioid withdrawal response if the patient is currently on an opioid and then takes buprenorphine. 

Suppose to be safer than methadone - no QT prolongation and less respiratory depression

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A 34 y/o m presents to the ED agitated and combative with the following vitals signs: T 104.6, P 136, BP 198/124. His urine toxicology screen is positive for amphetamines. 

• Controlled animal experience clearly contraindicates the use of phenothiazines (e.g. prochlorperazine, chlorpromazine) and butyrophenones (e.g. haloperidol, droperidol).
• In animal models, these drugs enhance toxicity (seizures) or lethality, or both.
• Additional concerns regarding these drugs include their ability to interfere with heat dissipation, exacerbate tachycardia, prolong the QTc interval, and induce torsades de pointes, or precipitate dystonic reactions.

Aripiprazole (Abilify): a new atypical antipsychotic partially agonizes D2 and serotonin receptors though its compelte mechanism is not known. Used in schizophrenia, in overdose you may see the following symptoms (from a retrospective study done over 4 years worth of calls to a PCC):

• Somnolence 89 (56%)
• Tachycardia 32 (20%, heart rate 102-186)
• Nausea/vomiting 29 (18%)
• Dystonic reactions 21 (13%)

The study was with over 255 patients. Though QT prolongation is listed, it is not common with this medication.

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     Most hand sanitizers contain ethanol, while some contain isopropyl alcohol. The concentration of alcohol in these products varies from 45% to 95%, with the most commonly used products containing 62%.  How much would a 15 kg child have to ingest to obtain a blood alcohol concentration of 100 mg/dL (or 0.1%)?

     Assuming a volume of distribution of 0.6 L/kg and 100% bioavailability, only 15-20 mL is required to produce this toxic level.  That is equivalent to 3-4 teaspoons or approximately 8-10 “squirts” of hand sanitizer!

WBI: whole bowel irrigation

Reminder from Poisondex:

OVERDOSE: SEVERE: Stupor, shock, acidosis, GI bleed, coagulopathy, hepatotoxicity, and coma. MILD/MODERATE: Nausea, vomiting, diarrhea, lethargy, leukocytosis, and hyperglycemia. Clinical phases: (1) 0-2 hours: Nausea, vomiting, diarrhea, and abdominal pain. Lethargy, shock, GI bleeding, and acidosis if severe; (2) Apparent recovery; (3) 2-12 hours: Acidosis, hypotension; (4) 2-4 days: Hepatotoxicity; (5) days-weeks: GI strictures.

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 Valproic Acid (Depakote)

• Can cause carnitine deficiency
• In overdose and therapeutic ingestions can cause hepatic enzyme elevation (idiosyncratic) but can also cause hyperammonemia without hepatic enyme elevation
• Have a patient with somnolence or altered mental status and is on valproic acid - check a level but also check an ammonia level
• Elevated ammonia levels can be treated with an antidote - carnitine (IV or PO)
• Very safe antidote (carnitine) since it is a nutritional supplement, consider in patients on valproic acid and decreased responsivness with elevated ammonia

Priapism - prolonged involuntary erection - is an adverse effect with some drugs. Here is a list of the more commonly reported:

• Androgens
• Anticoagulants
• Antihypertensives: Hydralazaine, labetolol, phentolamine, prazosin
• Antipsychotics
• Cantharidin
• Cocaine
• Diazepam
• Marijuana
• Sildenafil
• Trazadone
• Yohimbine

One of the treatment options for NYHA class III and IV pulmonary hypertension is prostanoids.  All of the prostanoid formulations have the limitations of a short half-life and a heterogeneous response to therapy.  Because the drugs need to be given by continuous infusion, patients may present to the ED due to pump failure.  Sudden cardiopulmonary collapse can occur with infusion interruption.  Here are some important points to remember regarding kinetics:

• Intravenous epoprostenol (Flolan®) has an extremely short half-life (2–3 min) and lacks stability at room temperature.  Interruption of the pump for even a short period can have drastic consequences.
• Treprostinil (Remodulin®) has theoretical advantages over epoprostenol because of its stability at room temperature, an elimination half-life of 4-6 hours (subcutaneous), and its ability to be administered by continuous subcutaneous infusion.

Vicks VapoRub Toxicity

With the removal of OTC product indications for children under the age of 2 for cough and colds, more parents are turning to other agents such as Vicks VapoRub for the relief of cough and cold symptoms. Unfortunately these agents are also associated with toxicities and the potential exists for an increased number of poisonings. The primary components of these agents are:

• Camphor
• Eucalyptus Oil
• Menthol

Menthol is used to relieve symptoms of chest congestion. There is NO data to support efficacy, and paradoxically, studies have indicated increased airflow resistance with application. There is a case report of an 18 month old who developed respiratory distress after application. Symptoms associated with overdose, or inappropriate route (mucosal, oral) are:

• Aspiration
• Apnea
• Laryngoconstriction
• Nausea
• Ataxia
• Cardiac and CNS toxicity (confusion, euphoria)

Camphor in products with higher concentrations such as Campho-phenique can cause additional toxicity with effects:

• GI symptoms
• CNS: confusion, hallucinations, excitation, coma, seizures
• Apnea
• Asystole

Treatment for both is supportive.
 

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To feed of off Dr. Liferidge's last pearl - a few more points relevant to your Emergency Department practice:

• Lidocaine toxicity ranges between 5-7mg/kg
• Typical vial used for suture repair is 10cc of 1% lidocaine. 
• 1% = (1g/100cc) thus 100mg lidocaine in one vial
• 70 kg x 5mg/kg = 350 mg typical adult toxic dose (3+vials)
• 10 kg x 5mg/kg = 50 mg peds toxic dose (<1vial)
• Case reports of viscous lidocaine (4%) causing seizures. Very classically in pediatric cases. Cause is from oral transmucosal absorption, bypassing the large first pass effect if absorbed from the stomach.
• Classic symptoms are termed "feeling drunk" progressing to seizure. Shortly after CNS effect can have suppression of intrinsic pacemaker leading to sinus arrest, AV block, hypotension and death

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