UMEM Educational Pearls - By Kathy Prybys

Category: Toxicology

Title: Hunan Hand

Keywords: Capsaicin, hunan hand, chili peppers (PubMed Search)

Posted: 10/6/2017 by Kathy Prybys, MD
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Hunan hand syndrome is a painful contact dermatitis that frequently presents in cooks and chili pepper workers after preparing or handling chili peppers. Contact with other body parts gives rise to the terms: "Hunan nose" ''Hunan eye",and "Chili Willie". Capsaicin, found in the fruit of plants from the genus Capsicum such as red chili peppers, jalapeños, and habaneros, is a hydrophobic, colorless, odorless compound that binds with pain receptors causing the sensation of intense heat or burning. The "heat" or pungency of a peppers is measured in Scoville heat units (SHU), the number of times a chili extract must be diluted with water to lose heat. Habanero peppers generate 30,000 SHU. Even at low concentrations capsaicin is a skin irritant. It is the primary ingredient in pepper spray used in law enforcement and in personal defense sprays.   

Treatment consists of decontamination with water irrigation for opthalmic exposure and milk or antacids for dermal or gastrointestinal exposure. Burning can be recurrent and of of long duration depending on tissue penetration. Topical anesthetic especially for the eye and cool compresses for the skin can relieve pain.  Parodoxically capsaicin is used as a topical analgesic medication for local pain relief from muscle pain, itching,  and painful neuropathies (diabetic, postherpetic). Capsaicin initially causes neuronal excitation followed by a long-lasting refractory period due to depletion of substance P, during which neurons are no longer responsive to a large range of stimuli and thus are desensitized.

 

 

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Category: Toxicology

Title: Drug Induced Hyperkalemia

Keywords: Hyperkalemia (PubMed Search)

Posted: 9/22/2017 by Kathy Prybys, MD (Updated: 10/5/2017)
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Hyperkalemia is a potentially life threatening problem which can lead to cardiac dysrhythmias and death.  Drug interactions inducing hyperkalemia are extremely common such as the combination of ACE inhibitors and spironolactone or ACE inhibitors and trimehoprim sulfamethoxazole. Hyperkalemia can also occur with a  single agent and is a relatively common complication of therapy with trimethoprim sulfamethoxazole. The following drugs can cause hyperkalemia:

  • Ace inhibitors
  • Beta blockers
  • Cyclosporine
  • Digitalis
  • Non-steroidal Anti-inflammatory Drugs
  • Pentamidine
  • Potassium supplement
  • Succinylcholine
  • Tacrolimus
  • Trimethoprim sulfamethoxazole 

 

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Category: Toxicology

Title: X-rays in poisoning diagnosis?

Keywords: Radiographs, poisoning (PubMed Search)

Posted: 9/7/2017 by Kathy Prybys, MD (Emailed: 9/8/2017) (Updated: 9/8/2017)
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Question

Radiographs studies can be valuable in poisoning diagnosis, management, and prognosis.  Radiographic imaging should be utilized for the following toxins:

Heavy metals 
  • Iron (gastrointestinal)
  • Mercury (gastrointestinal, intravenous or subcutaneous)
  • Lead (bullets intraarticular, gastrointestinal foreign bodies, lead lines)
  • Zinc phosphide (gastrointestinal)

Container toxins - Body packers

  • Drug packets and vials

Sustained Released preparations

  • Potassium Chloride
Button Batteries and Coins

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Category: Toxicology

Title: Deadly in a drop!

Keywords: Botulinum, Dimethylmercury, VX, Tetrodotoxin (PubMed Search)

Posted: 8/17/2017 by Kathy Prybys, MD (Emailed: 8/31/2017) (Updated: 8/31/2017)
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Botulinum
  • Most poisonous substance known to man
  • LD50 oral dose 1 mcg/kg
  • Heat labile single polypeptide chain undergoes proteolytic clevage irreverisibly binds  and blocks cholinergic transmission causing a deadly neuroparalytic syndrome
  • Rx: Botulin antitoxin (equine derived against Clostriduim botulinum A,B,E)
Dimethylmercury (CH3)2 Hg
  • Highly toxic, restricted availability is rapidly absorbed and metabolized to methylmercury crosses CNS
  • LD50 of 50 mcg/kg means a dose as little as 0.1ml can result in severe poisoning
  • Death of Darmouth inorganic chemist Karen Wetterhahn who spilled a few drops on back of her latex gloved hand, quickly permeated, and absorbed causing severe neurotoxocity and death 10 months later
  • Rx: Chelation

VX ("venomous agent X") 

  • Organophosphate nerve agent has been used as chemical weapon
  • Colorless, odorless, low volatility, and high lipophilicity
  • LD50 of 0.04mg/kg (10 mg). Death can occur within 15 minutes after absorption
  • Blocks acetylcholinesterase enzyme causing excess accumulation of acetylcholine at the neurojunction and cholinergic poisoning
  • Rx: Decontamination, Atropine, 2-PAM
Tetrodotoxin
  • 100 fresh and salt water varieties (pufferlike fish/blue ringed octopus, frogs)
  • Heat stable, water soluble found in fish skin, liver, ovaries,intestine, and muscle
  • 25 mg (0.000881 oz) expected to be lethal to a 75 kg person
  • Neurotoxicity by inhibition of Na-K pump and blockade neuromuscular transmission
  • Rx: Supportive measures

LD50 expresses the dose at which 50% of exposed population will die as a result of exposure.

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Category: Toxicology

Title: Vaginal Detox?

Keywords: Vaginal pearls, intravaginal foreign bodies (PubMed Search)

Posted: 7/20/2017 by Kathy Prybys, MD (Emailed: 7/21/2017) (Updated: 7/21/2017)
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Question

Vaginal douching is a common and potentially dangerous practice. Women engage in this practice predominately for personal hygiene reasons but also with the false belief it will prevent or treat infections and for contraception. Numerous public health agencies and medical societies discourage douching as it has been associated with many adverse outcomes including pelvic inflammatory disease, bacterial vaginosis, cervical cancer, low birth weight, preterm birth, human immunodeficiency virus transmission, sexually transmitted diseases, ectopic pregnancy, recurrent vulvovaginal candidiasis, and infertility.

An increasing fad is the use of intravaginal detox products. Claiming to enhance female health by removing toxins, these mesh cloth-covered balls containing herbs such as mothersworth, osthol, angelica, borneol, and rhizoma, not FDA-approved, are inserted into the vagina for 3 days. Clinical experience demonstrates these products decompose into numerous pieces which become scattered retained intravaginal foreign bodies, cause mucosal irritation, and thereotically could serve as a nidus for serious infections.

 

 

 

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Serious outcomes after overdose or nonintentional exposures to medications used to treat depression have risen dramatically over the past 15 years. Morbidity and mortality associated with drugs used to treat depression were studied utilizing the National Poison Data System from 2000-2014. Tricyclic and monoamine oxidase inhibitor medications were associated with the highest morbidity and mortality. Newer agents such as Lithium, venlafaxine, bupropion, quetiapine, olanzapine, ziprasidone, valproic acid, carbamazepine, and citalopram were also associated with higher mortality indices.

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Category: Toxicology

Title: Black Widow Bite

Keywords: Lactrodectus (PubMed Search)

Posted: 6/29/2017 by Kathy Prybys, MD (Emailed: 6/30/2017) (Updated: 6/30/2017)
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 Black widow  spiders belong to the genus Latro dectus which include 31 species of widow spiders found throughout world. Approximately 1500-2500 black widow bites are reported to American poison control centers annually. A black widow can be identified by their hourglass pattern (red or orange) on the ventral aspect of their shiny globular abdomen. Fortunately, envenomation is rare but when it does occur it causes severe pain, muscle cramping, abdominal (may mimic acute abdomen) often refractory to traditional analgesics and antivenom (Antivenin Latrodectus mactans) is available and effective . Alpha-latrotoxin is the potent toxin causing presynaptic cation channels to open (calcium) and release of neurotransmitters such acetycholine. The neurological signs and symptoms caused by predominantly autonomic and include tachycardia and hypertension. The antivenom is equine based and infused over 20-30 minutes with pain relief in 20 minutes.

 

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Category: Toxicology

Title: "Triple C" Overdose

Keywords: Dextromethorphan, Robotripping (PubMed Search)

Posted: 4/20/2017 by Kathy Prybys, MD (Emailed: 4/27/2017)
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Question

A 17 y/o male presented for altered mental status. His mother stated she was contacted by neighbor concerned that her son was wandering down the middle of a local roadway. His friends stated he had taken 16-17 "triple C's" in an attempt to "get high". No other coingestants were identified. At presentation, the patient appeared to be in an toxic delirium. VS : 187/112, 116, 16, 98.9, 100% RA. Patient  was awake with eyes open but slowly responsive.GCS was 12. No evidence for trauma. Pupils were dilated and slowly reactive. The rest of the exam was essentially negative.
 
  • Coricidin Cough & Cold medicine also known by street name 'Triple C" is the most commonly reported abused dextromethorphan-containing product.
  • Dextromethorphan at high doses acts as a dissociative general anesthetic and hallucinogen similar to Ketamine and Phencyclidine (PCP) by antagonizing the NMDA receptor in a dose dependent manner.
  • Detromethorphan-containing products are appealing to teens as they are easily available (OTC), legal, inexpensive, and preceived as safe. 
  • Street names for dextromethorphan products include DXM, CCC, Trile C, Skittles, Robo, Poor Man's PCP,. Abuse of Robitussin products is referred to as "Robotripping"
  • Additional toxicity can occur from the coingredients (pseudoephedrine, acetaminophen, and antihistamines such as Chlorpheniramine) is a serious concern of taking large amounts of OTC cough and cold medications for the Dextromethorphan content. Chlorpheneriamine is a  first generation H1-histamine receptor antagonist with potent antimuscarinic properties.
  • Dextromethorphan is not detected by basic drug screens and should be considered when evaluating patients with a dissociative toxidrome. Acetaminophen levels should be obtained.
  • No specific antidote exists for dextromethorphan toxicity. Benzodiazepines should be administered for seizures and aggressive cooling measures for hyperthermia. Naloxone can be considered for use in patients in a coma or with respiratory depression but variable results are reported.
 

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Category: Toxicology

Title: Pediatric poisoning trends

Keywords: Pediatric poisoning, household , fatalities (PubMed Search)

Posted: 3/30/2017 by Kathy Prybys, MD
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Children less than 5 years of age account for the majority of poisoning exposures in the United States. As expected, accessible household items are the most frequently reported exposures and include cosmetics and personal care products, household cleaning substances, medications, and foreign bodies. Opioids are responsible for the highest incidence of hospitalizations followed by benzodiazepines, sulfonylureas, and cardiovascular drugs (beta & calcium channel blockers, and centrally acting antiadrenergic agents).  Rise in buprenorphine use has led to significant increases in pediatric exposures. The most common sources of prescription medications were pills found on the ground, in a purse or bag, night stand, or pillbox. The 2015 American Association of Poison Centers Annual report lists 28 fatalities in children less than 5 year of age. Fatalities occurred from exposures to the following: narcotics (9), disc and button batteries (5), carbon monoxide (4), and other substances (10). 

Highlighted AAPC cases include:

  •  20 month old with ingestion of 20 mm Lithuim disc battery with several previous ED visits for abdominal pain who developed an aorto-esophageal fistula 
  • 13 month old with ingestion of unknown amount of salicylate pills 4 hours earlier with nausea and vomiting
  • 2 year old with ingestion of 5 tablets of 30mg Oxycodone ER seen in ED and discharged 7 hours later. EMS called next morning found patient unresponsive and apneic
  • 11 month old with ingestion of 1 unknown strength methadone pill found unresponsive and apneic at home

Poison prevention education of patients prescribed opioids or other highly toxic "one pill killers"  who have young children in their household is recommended and could be potentially life saving.

 

 

 

 

 

 

 

 

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Category: Toxicology

Title: Acute Phenytoin Toxicity

Keywords: Dilantin, Ataxia (PubMed Search)

Posted: 3/16/2017 by Kathy Prybys, MD
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Phenytoin is a first line anticonvulsant agent for most seizure disorders with the exception of absence and toxin-induced seizures. It has erratic gastrointestinal absorption with peak serum levels occurring anywhere from 3-12 hours following a single oral dose. 90% of circulating phenytoin is bound to albumin but only the unbound free fraction is active to cross cell membranes and exert pharmacological effect. Measured serum phenytoin levels reflect the total serum concentration of both the free and protein bound portions. Therapeutic range is between 10-20 mg/L. Free phenytoin levels are not often measured but are normally between 1-2 mg/L. Individuals with decreased protein binding (elderly, malnourished, hypoalbuminemia, uremia, and competing drugs) may have clincial toxicity despite a normal total phenytoin level. Toxicity consists of predominantly ocular and neurologic manifestations involving the vestibular and cerebellar systems:

Plasma level, µg/mL    Clinical manifestations
<10     Usually none
10-20     Occasional mild nystagmus
20-30     Nystagmus
30-40     Ataxia, slurred speech, extrapyramindal effects 
40-50     Lethargy, confusion
>50     Coma, rare seizures

Treatment of overdose is primarily supportive with serial drug level testing and neurologic exams. There is no evidence that gastrointestinal decontamination improves outcome. Routine cardiac monitoring is not necessary for overdose following oral ingestions. Cardiac toxicity is rarely seen and only with parenteral administration. 

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Category: Toxicology

Title: Drug induced Excited Delirium

Keywords: EDS, Excited Delirium (PubMed Search)

Posted: 3/2/2017 by Kathy Prybys, MD
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Excited delirium syndrome (EDS) is a life-threatening condition caused by a variety of factors including drug intoxication.  EDS is defined as altered mental status, hyperadrenergic state, and combativeness or aggressiveness. It is characterized by tolerance to significant pain, tachypnea, diaphoresis, severe agitation, hyperthermia, non-compliance or poor awareness to direction from police or medical personnel, lack of fatigue, superhuman strength, and inappropriate clothing for the current environment. These patients are at high risk for sudden death. Toxins associated with this syndrome include:

  • Lysergic acid diethylamide (LSD)
  • Phencyclidine (PCP)
  • 3,4-methylenedioxymethamphetamine (Ecstasy)
  • Cocaine
  • Methamphetamine
  • Synthetic cathinones ("Bath salts")Mephedrone, Methylone,  Methylenedioxypyrovalerone (MDPV), designer drugs similar to amphetamine.
  • Synthetic cannbinoids

Ketamine at 4mg/kg dose can be given by intramuscular route and has been demonstrated to be safe and effective treatment for EDS.

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Category: Toxicology

Title: Suboxone for managing opioid addiction

Keywords: Buprenorphine, Suboxone (PubMed Search)

Posted: 2/16/2017 by Kathy Prybys, MD
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Question

The current opioid epidemic is considered the worst drug crisis in American history responsible for 50,000 deaths per year in the US from overdose of heroin and opioid prescription drugs. A 200% increase in the rate of overdose deaths involving opioids occurred between 2000 and 2014. The continued rise in opioid related deaths calls for an urgent need for treatment. Three types of medication-assisted therapies (MATs) are available for treating patients with opioid addiction:methadone, buprenorphine, and naltrexone. Suboxone a combination of buprenorphine and naloxone, is emerging as one of the best choices for the following reasons:

  • Buprenorphine is a partial agonist that suppresses opioid withdrawal and cravings.
  • Binds opioid receptors with high affinity but low intrinsic activity.
  • Lasts 24 hours. Binds opioid receptors to prevent full opioid agonists such as heroin or prescription opioids from binding.
  • Less risk for dependency as increasing doses does not result in full opioid effect.
  • Less respiratory depression in overdose due to partial effect.
  • Naloxone, an opioid antagonist is poorly absorbed by oral route and is added to discourage injecting or snorting of suboxone as it can precipitate severe withdrawal.
  • Precipitated withdrawal can occur if other opioids are present with administration of Suboxone. This is particularly important with long acting opioids such as methadone.
  • Can be prescribed in the primary care setting and does not require a specialized clinic.
  • Comes in 2 or 8 mg tablet or sublingual film.

 

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Category: Toxicology

Title: Urine drug testing

Keywords: Urine Drug Sreen (PubMed Search)

Posted: 1/19/2017 by Kathy Prybys, MD (Emailed: 1/20/2017) (Updated: 1/20/2017)
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Urine drug screens are most commonly performed by immunoassay technology utilizing monoclonal antibodies that recognizes a structural feature of a drug or its metabolites.  They are simple to perform. provide rapid screening, and qualitative results on up to 10 distinct drug classes with good sensitivity but imperfect specificity. This can lead to false positive results and the need for confirmatory testing. UDS  does not detect synthetic opiates or cannabinoids, bath salts (synthetic cathinones), and  gamma-hydroybutyrate. Most common drug classes detected are the following:

  • Opiates
  • Methadone
  • Benzodiazepines (not all)
  • Amphetamines 
  • Cocaine
  • THC metabolites
  • Barbituates
  • LSD
  • PCP
  • MDMA (Ecstasy)

 

 

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Category: Toxicology

Title: Unexplained Lactic Acidosis, a clue to poisoning

Keywords: Lactic acidosis (PubMed Search)

Posted: 1/5/2017 by Kathy Prybys, MD (Emailed: 1/6/2017) (Updated: 1/6/2017)
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Lactic acidosis is the most common cause of anion gap metabolic acidosis in all hospitalized patients. An elevated lactate level is an important marker of inadequate tissue perfusion causing subsequent shift to anaerobic metabolism and occuring in a variety of disease states such as sepsis. In patients with unexplained lactic acidosis without systemic hyoperfusion or seizure suspect  the following toxins:

  • Acetaminophen: Early on in massive ingestion usually associated with coma.
  • Cyanide
  • Metformin
  • HIV Drugs: Nucleotide reverse transcriptase inhibitors = Didanosine, stavudine, zidovudine due to mitochondrial toxicity.
  • Ethylene Glycol: Spuriously elevated lactate may occur with ethylene glycol toxicity due to the structural similarity between glycolic acid and lactate.Check for osmolar gap.
  • Kombucha ``mushroom'' tea 
 

 

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Category: Toxicology

Title: Acetaminophen induced liver failure

Keywords: Acetaminophen, Liver Failure (PubMed Search)

Posted: 12/16/2016 by Kathy Prybys, MD
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Acetaminophen is one of the most common pharmaceutical ingestions in overdose and a leading cause of acute of liver failure in the U.S.  Early recognition and treatment is critical for prevention of morbidity.

  • Vigilance and screening is required for this "silent poison", available in hundreds of OTC products and in combination with numerous prescription medications. Symptoms may not be present early in course (for up to 24 hours) in poisoning.
  • Maximal benefit with antidote treatment, n-acetylcysteine (NAC) is time dependent within 8 hours of ingestion. Fulminant hepatotoxicity is unusual in acute overdoses treated with NAC within 10 hours of ingestion.
  • Early prediction of poor prognosis is essential to identify patients who may require life-saving liver transplantation.  Kings College Criteria: Arterial pH less than 7.30, INR greater than 6.5, Creatinine greater than 3.4, Grade III or IV encephalopathy combined with Lactate greater than 3.5 and Phosphate greater than 3.75 may increase sensitivity.

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Category: Toxicology

Title: My patient really has all these drug allergies?

Keywords: Drug Allergy, ADR, ADE (PubMed Search)

Posted: 12/1/2016 by Kathy Prybys, MD (Emailed: 12/2/2016) (Updated: 12/2/2016)
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Question

Misclassification of adverse drug effects as allergy is commonly encountered in clinical practice and can lead to use of suboptimal alternate medications which are often less effective.

  • Nomenclature surrounding drug safety needs to be clear and unambiguous to avoid confusion. 
  • Adverse Drug Effect (ADE) = All drug induced disease. Majority are predictable based on drug's known pharmacology. Include harm related to medication errors and drug/food interactions. 
  • Adverse Drug Reaction (ADR) = Noxious or unintended reaction to a drug that is administered at therapeutic doses during normal use. Divided into predictable (majority 75-80%), related to pharmacologic actions of the drug in otherwise normal individuals) and unpredictable reactions (related to individual’s immunological response). 
  • "Drug allergies"  are relatively uncommon with cited incidence of 10%. Immunologically mediated reactions (type I to IV) to a pharmaceutical and/or formulation (excipient) in a sensitized person. They are dose independent and unrelated to pharmacological action of the drug. Most commonly, IgE-mediated type I (immediate) reactions caused by rapid release of vasoactive mediators from mast cells and peripheral basophils causing generalized reaction including urticaria, angioedema, stridor, wheezing, and cardiovascular collapse.
  • The skin is the most frequently and notably affected by drug induced allergic reactions.
  • Antibiotics, particuarly Beta-Lactams, are the most important cause of immediate hypersensitivity reactions. Approximately 10% of patients report a history of penicillin allergy, however after complete evaluation, up to 90% of these individuals are able to tolerate penicillin and are designated as having “penicillin allergy” unnecessarily.
  •  Pseudoallergy can occur with opioids due to histamine release. Codeine and morphine are most commonly associated with pseudoallergy. Coadministration of an antihistamine or use of a semi or synthethic opioid (Fentanyl, hydromorphone) can prevent this reaction.

 

 

 

 

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Category: Toxicology

Title: "Leaves of 3 let them be"

Keywords: Poison Ivy, Toxicodendron, Urushiol (PubMed Search)

Posted: 10/6/2016 by Kathy Prybys, MD (Emailed: 10/7/2016) (Updated: 10/7/2016)
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Question

Fall clean up = Poison Ivy, oak, sumac (Toxicodendron species) which is ubiquitous in North America but it can also be found in British Columbia, Mexico and in parts of Asia. These plants are truly the scourge of outdoor enthusiasts and agricultural workers responsible for up to 40 million cases of miserable often temporarily incapacitating rashes annually.

Fast Facts:

  • Grows as plant, vine, or shrub with leaves ranging in color from light or glossy green to red and yellow in fall.
  • Exposure by direct contact with plant, indirectly from oil resin on objects, clothes, pets, or airborne from burning plant.
  • Urushiol toxin induced type IV hypersensitivity allergic contact dermatitis. This oily resin toxin is excreted from all parts of plant (stems, leaves, flowers, roots, vines). and is extremely stable staying active even after plant dies.
  • Intensely itchy blistering rash starts 12-72 hours after contact and lasts up to 21 days. Characterized by red streaks or linear configuration where skin brushed up against plant sap. Inflammation (redness, swelling, hives, blistering) to thick leathery plagues depending on severity and vulnerability of skin location. Intense inflammation can mimic cellulitis.
  • Rash is Not contagious but spread of oil on clothes, pets, tools, objects is!
  • Delayed reaction accounts for seemingly "spread" of rash. Eruption rate depends on thickness of skin and dose of urushiol oil.

Treatment Tips:

  • Prevention. Avoidance and universal precautions when gardening. Clusters of 3 leaves each trio growing on their own stem, hairy vines, no thorns, white berries.
  • Cover skin to prevent exposure and if known contact immediately wash skin, clothes, objects.
  • Hot water relieves itch as does cool compresses.
  • Domeboro or witch hazel are astringents can reduce inflammation.
  • External analgesics (e.g., benzocaine, lidocaine, benzyl alcohol) can help itching.
  • Highly viscous or granular cream surfactant washes bind urushiol and can reduce exposure. Zanfel, Mean green, Gojo orange, various generic poison ivy removal scrubs now available. (Zanfel works wonders used every few hours and may alleviate need for steroids but is $$$ and several tubes are required).
  • In severe cases, Steriod burst followed by 2-3 week taper to prevent relapse flare.

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Drug-induced hypoglycemia is an often severe and symptomatic. It is a potentially preventable cause of significant morbidity. In one large study, it accounted for 23% for hospital admissions due to adverse drug events and 4.4% of overall admissions. The majority of hypoglycemic events occur with insulin and sulfonylureas. However, multiple drugs can affect glucose homeostasis and have been cited to cause hypoglycemia in therapeutic dose alone or in combination with other medications or illness. Factors that predispose to low blood sugar include reduced food intake, age, hepatic and renal disease, and severe infection. Beware of the possibility of inducing hypoglycemia in patients taking the following:

  • Ethanol
  • Insulin
  • Pentamidine
  • Quinine
  • Quinolones (Gatifloxin others rare)
  • Sulfonylureas

Agents with lesser quality evidence as predisposing medications or illnesses were present:

  • Ace Inhibitors (with diabetic agents)
  • Propanolol ( less likely in other beta blockers)
  • Trimethoprim/sulfamethoxazole (in renal compromise)
  • Salicylates (high dose or intoxication)

Drugs induced hypoglycemia should always be considered in the differential diagnosis of every patient presenting with low blood glucose. Octreotide antagonizes pancreatic insulin secretion and should be considered for first-line therapy in the treatment of sulfonylurea-induced hypoglycemia particularly when glucose levels cannot be maintained by dextrose infusions. Octreotide is administered 50 mcg subcutaneously (1-10 mcg in children) every 12 hours.

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Category: Toxicology

Title: Bupropion Toxicity

Keywords: Bupropion, Seizure, Cardivascular instability (PubMed Search)

Posted: 6/2/2016 by Kathy Prybys, MD (Emailed: 6/3/2016) (Updated: 6/3/2016)
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Bupropion (Wellbutrin, Zyban) is one of the most frequently prescribed antidepressants and smoking cessation agents. A lesser incidence of undesirable side effects such as weight gain and sexual dysfunction when compared to other antidepressants lends to its popularity. Bupropion's mechanism of action is only partially understood but it is known to be a norepinephine dopamine reuptake inhibitor and anticholinergic receptor blocker at certain nicotinic receptors. Bupropion has a monocyclic structure similar to amphetamines. Seizures are a major concern in overdose. When first released, Bupropion was initially withdrawn from the market due to its narrow therapeutic window with seizures occurring at doses as low as 450 mg.

  • Seizures are dose dependent and all types can occur. Incidence increases dramatically with higher doses. Benzodiazepines are first-line therapy.
  • Most patients experience seizure within 8 hours however, seizures can occur up to 24 hours after ingestion even without preceding symptoms.
  • Longer acting forms: SR, XL, ER cause prolonged toxicity and activated charcoal should be administered in the absence of contraindications (depressed mental status, lack of airway protection, seizure).
  • Myocardial sodium channel blocking properties occur and sodium bicarbonate should be administered when this occurs.
  • Cardiovascular effects including tachycardia, prolonged QT interval, QRS widening, arrhythmia, and cardiovasular collapse.
  • Bupropion is extremely lipid soluble and intravenous lipids should be considered in severe poisonings. Intralipid has been successfully used in several cases of Bupropion poisoning with cardiovascular instability or severe CNS symptom with good outcomes.

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Category: Toxicology

Title: Ketamine for Severe Undifferentiated Acute Agitation

Keywords: Ketamine, Benzodiazepines (PubMed Search)

Posted: 4/7/2016 by Kathy Prybys, MD (Emailed: 4/8/2016) (Updated: 4/8/2016)
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[CORRECTION]: Versed dose is 2-2.5 mg total not mg/kg

Patients with severe agitation present a unique challenge to the emergency department. Acute delirium is often due to psychostimulants such as cocaine, amphetamines, PCP, or synthetic cannabinoids, alcohol, or psychiatric illness. These patients require urgent evaluation necesssitating the use of physical and chemical restraints, not only for their own safety but also the hospital staff's. Fingerstick glucose, pulse oximetry, and vital signs must be expeditiously obtained. Severely agitated combative patients who are physically restrained are at high risk for morbidity from asphyxiation, hypermetabolic consequences (acidosis, hyperthermia, rhabdomyolysis), and death can occur.

Ketamine is phencyclidine derivative that causes dissociative state between the cortical and limbic systems which prevents the higher centers from preceiving visual, auditory, or painful stimuli. Ketamine has a wide safety profile and has been used worldwide for many years with few complications. It possesses ideal characteristics for rapid sedation of agitated patients:

  • Rapid onset of action 1-3 minutes
  • Preservation of airway reflexes
  • Lack of respiratory or cardiac depression or QT prolongation
  • Short half-life of 30-40 minutes
  • Safe in situations with minimal to no monitoring
  • Dose: Intravenous =1.5-2 mg/kg Intramuscular = 5-6 mg/kg (maximum 400 mg)

Experience with Ketamine in patients with excited delirium has shown good initial control of agitation however, patients often require additional medications for deeper or longer duration of sedation. Benzodiazepines are recommmended as second line agents particularly intravenous or intramuscular Midazolam 2-2.5 mg /kg.

 

 

 

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