UMEM Educational Pearls - Toxicology

Category: Toxicology

Title: Loperamide Cardiac Toxicity

Keywords: Loperamide, cardiotoxicity, QT prolongation (PubMed Search)

Posted: 12/7/2017 by Kathy Prybys, DO (Emailed: 12/8/2017) (Updated: 12/8/2017)
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Loperamide (Imodium) is a common inexpensive over-the counter antidiarrheal agent. It acts peripherally at the mu opioid receptor to slow gastrointestinal motility and has no CNS effects at therapeutic doses due to it's low bioavailability and limited abillity to cross the blood brain barrier dependent on glycoprotein transport. In the past few years, reports of loperamide abuse causing serious cardio toxicity began to appear in the literature. Abused at daily doses of 25-200 mg to get high or and to treat symptoms of withdrawal. (therapeutic dose: 2-4 mg with a maximun of 8mg for OTC and 16mg for prescription). Loperamide has been called the "poor man's methadone".

At large doses, loperamide effects the cardiac sodium, potassium and calcium channels which prolongs the QRS complex  and can lead to ventricular arrhythmias, hypotension, and death. Clinical features includes:

  • QT prolongation
  • QRS widening
  • Ventricular arrythmias
  • Hypotension
  • Syncope
  • CNS depression


Take Home Point:

Consider loperamide as a possible cause of unexplained cardiac events including QT interval prolongation, QRS widening, Torsades de Pointes, ventricular arrhythmias, syncope, and cardiac arrest. Intravenouse sodium bicarbonate should be utilized to overcome blockade and may temporize cardiotoxic events. Supportive measures necessary may include defibrillation, magnesium, lidocaine, isoproternol, pacing, and extracorporeal life support.



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Different chemical, food or pharmaceutical agent exposure can change the color of the urine.

What could cause this patient's urine to turn green?

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Category: Toxicology

Title: When to hemodialyze in Lithium Toxicity

Keywords: Hemodialysis, lithium (PubMed Search)

Posted: 11/16/2017 by Kathy Prybys, DO (Emailed: 11/17/2017) (Updated: 11/17/2017)
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Lithium salts have been used therapeutically for over a 150 years to sucessfully treat manic depressive symptoms, schizoaffective disorder, and cluster headaches. Lithium has a narrow therapeutic range (0.6-1.5 meq/L) and is 100% eliminated by the kidneys. Multisystem toxicity occurs however CNS toxicity is significant and consist of confusion, lethargy, ataxia,  neuromuscular excitability (tremor, fasciculations, myoclonic jerks, hyperreflexia). Since there is a poor relationship between serum concentration and toxicity in the brain, serum blood levels may not reflect extent of toxicity . The goal of enhanced elimination is to prevent irreversible lithium-effectuated neurotoxcity which causes persistant cerebellar dysfunction with prolonged exposure of the CNS to high lithium levels.

Decision for hemodialysis is determined by clinical judgement after considering factors such as lithium  concentration, clinical status of patient, pattern of lithium toxicity (acute vs. chronic), concurrent interacting drugs, comorbid illnesses, and kidney function. Strongly consider hemodialysis for the following: 

  • Manifestations of severe lithium poisoning
  • Impaired kidney function
  • Decreased level of consciousness, seizures, or life threatening dysrhythmias irrespective of lithium concentration
  • Lithium level greater than 5


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Category: Toxicology

Title: Do you have digoxin-like toxins growing in your backyard?

Keywords: cardioactive steroids, cardioactive glycoside (PubMed Search)

Posted: 11/9/2017 by Hong Kim, MD, MPH (Updated: 5/29/2023)
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Many medications are discovered from plants (quinine – cinchona trees) or organisms (penicillin – mold [penicillicum]).

Digoxin was isolated from foxglove (Digitalis lanata), a colorful floral plant often found in many gardens.  There are other sources of cardioactive steroids (aka cardiac glycosides) that have similar effect as digoxin.

  • Oleander (Nerium oleander)
  • Yellow orleaner (Thevetia peruviana) – frequently used for suicide in Southeast Asia
  • Lily of the valley (Convallari majalis) – use in wedding bouquet
  • Dogbane (Apocynum cannabinum)
  • Red squill (Urginea maritima)
  • Bufo toad (Bufo species)  


Non-digoxin cardioactive steroid exposure can result in a positive digoxin level due to cross reactivity. This confirms exposure; however, the “digoxin level” does not represent the true extent of the ingested dose or toxicity. 

Non-digoxin cardioactive steroid toxicity

  • Digibind also binds to non-digoxin cardioactive steroids.
  • However, larger doses are often required (initial dose: 10 to 20 vials) than doses required for digoxin toxicity.   

The cornerstone treatment of poisoning is removal of the toxin from the patient. This can be accomplished before absorption into the body by decontamination methods (dermal or gastrointestinal) or after absorption by blocking metabolism of parent compound, displacing drugs from receptors, binding toxins with neutralizing agents (chelators, Fab fragments), or enhancing elimination by dialysis. Toxins that are ideal candidates for dialysis include substances that are low molecular weight, have low volume of distribution (stay in the blood stream), or low protein binding. Toxins most commonly treated with dialysis are:

  • Lithium
  • Salicyclates
  • Ethylene glycol
  • Methanol
  • Acetaminophen

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Category: Toxicology

Title: Agatha Christie 2.0 Strychnine

Keywords: strychnine (PubMed Search)

Posted: 10/26/2017 by Hong Kim, MD, MPH (Emailed: 10/27/2017) (Updated: 10/27/2017)
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Her first book “The mysterious affair at Styles,” Agatha Christie introduced her lead detective in her novels, Hercule Poirot - the Belgian detective.  She also described the death of Mrs. Emily Inglethorp by strychnine.

Strychnine is found in a disc-like seed of strychnos nux-vomica, a tree native to tropical Asia and North Australia.

It is currently used as rodenticide (moles and gophers), in Chinese herbal medicine and a traditional remedy in Cambodia.

Strychnine inhibits binding of glycine (a major inhibitory neurotransmitter in spinal cord) to Cl-channel resulting in identical clinical syndrome – seizure-like generalized muscle contraction with normal mental status – as tetanus toxin. Tetanus toxin inhibits the release of presynaptic glycine in the spinal cord. 



Goal: decrease muscle hyperactivity

  • 1st line: benzodiazepine
  • 2nd line: barbiturates or propofol
  • 3rd line: paralysis by non-depolarizing agents

Category: Toxicology

Title: Arsenic and Agatha Christie

Keywords: Arsenic poisoning (PubMed Search)

Posted: 10/19/2017 by Hong Kim, MD, MPH
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Agatha Christie is an English crime novelist who frequently used poisons in her books to murder the victims. In her book, Murder is Easy, Ms. Christie uses arsenic/arsenic trioxide to kill several characters.


Primary source of arsenic in general population is contaminated food, water and soil. Arsenic exists in several forms: elemental, gaseous (arsine), organic and inorganic (trivalent or pentavalent).


Arsenic trioxide has also been used to treat acute promyelocytic leukemia in China; it’s use in other leukemia, lymphoma, and other solid tumors are currently being investigated.


Arsenic primarily inhibits the pyruvate dehydrogenase complex and multiple other enzymes involved in the citric cycle/oxidative phosphorylation, resulting in mitochondrial dysfunction.


Acute toxicity of arsenic after ingestion

  1. GI symptoms (minutes to several hours) – nausea, vomiting, abdominal pain and cholera like diarrhea.
  2. Cardiovascular: QT prolongation/torsade de pointes, orthostatic hypotension, ventricular dysrhythmias, myocardial dysfunction and shock.
  3. CNS (days): encephalopathy, delirium, coma, and seizure due to cerebral edema and microhemorrhages.
  4. Respiratory: ARDS, respiratory failure,
  5. Others: AKI, leukemoid reaction, hemolytic anemia, and hepatitis.



  1. Chelation: dimercaptrol (BAL) or succimer
  2. Whole bowel irrigation if radiopaque material is present (abdominal XR)
  3. Electrolyte and fluid management
  4. Cardiac monitoring and pressor support in hypotension

Category: Toxicology

Title: Cannabinoid Hyperemesis Syndrome

Keywords: Cannabinoid, cyclic vomiting, Capsaicin (PubMed Search)

Posted: 10/12/2017 by Kathy Prybys, DO
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Cannabinoid hyperemesis is a syndrome (CHS) characterized by severe intractable nausea, cyclical vomiting, and abdominal pain associated with chronic marijuana abuse. It is often a underrecognized cause of cyclic vomiting syndrome. Despite well established anti-emetic properties of marijuana, paradoxical effects on the GI tract exist through cannabinoid receptors which exert their neuromodulatory properties in the central nervous system and the enteric plexus. Multiple theories of mechanism of CHS are in the literature. Diagnosis is based on the following clinical criteria:

  • History of regular cannabis for any duration of time
  • Refractory nausea and vomiting
  • Gastrointestinal evaluations fail to identify other clear causes
  • Compulsive bathing in hot water temporarily alleviates symptoms often done several times a day. A red flag symptom.
  • Resolution of symptoms after cannabis is discontinued

Acute care goals are to treat dehydration and terminate nausea and vomiting. Administration of intravenous fluids, dopamine antagonists, topical capsaicin cream, and avoidance of narcotic medications are recommened treatment measures. Benzodiazepines followed by haloperidol and topical capsaicin are reported to be most effective. Capsaicin  activates the transient receptor potential vanilloid 1 receptors (TRPV1) which impairs substance P signalling in the area postrema and nucleus tract solitarius similar to noxious stimuli, such as heat. 

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Category: Toxicology

Title: Hunan Hand

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

Posted: 10/6/2017 by Kathy Prybys, DO
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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, DO (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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During the past several years, several new classes of diabetic medications were introduced for clinical use, including SGLT2 inhibitors (canagliflozin, dapagliflozin and empagliflozin).

SGLT2 inhibitors prevent reabsorption of glucose in the proximal convoluted tubules in the kidney and does not alter insulin release.

A recent retrospective study (n=88) of 13 poison center data from January 2013 to December 2016 showed

  1. 91% of the patients were asymptomatic.  
  2. 7% developed minor symptoms (tachycardia, nausea/vomiting, abdominal pain, & confusion)
  3. 2% developed moderate symptoms (metabolic acidosis, hypertension [166/101], & hypokalemia)
  4. Hypoglycemia was not reported.

49 patients were evaluated in a health care facility (HCF) with 18 admissions. Referral to HCF was more common in pediatric patients. This was likely due to unfamiliarity with a new mediation and lack of toxicity data.

Other case reports have shown higher incidence of DKA with the therapeutic use of SGLT2 vs. other classes of DM medications.


Bottom line:

Limit data is available regarding the toxicologic profile of SGLT2 inhibitors.

Based upon this small retrospective study, hypoglycemia may not occur and majority of the patient experience minimal symptoms.

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Category: Toxicology

Title: X-rays in poisoning diagnosis?

Keywords: Radiographs, poisoning (PubMed Search)

Posted: 9/7/2017 by Kathy Prybys, DO (Emailed: 9/8/2017) (Updated: 9/8/2017)
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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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There have been reports of “intoxication” or adverse effects among first responders and law enforcement due to exposure to a “powder” suspected to be fentanyl or its analog.


This has led to a significant concern among first responders and law enforcement when investigating or handling “powder” at the scene of overdose or drug enforcement related raids. (


American College of Medical Toxicology and American Association of Clinical Toxicology recently published a position statement to help clarify the potential health risk associated with exposure to fentanyl and its analogs.


  1. Opioid toxicity is unlikely from incidental dermal exposure.
  2. Nitrile gloves provide sufficient protection against dermal exposure.
  3. N95 respirator provide sufficient protection against aerosolize fentanyl/opioids.
  4. Naloxone should be administered for patients with objective signs of opioid toxicity - hypoventilation and CNS depression – not for vague or subjective symptoms.

Category: Toxicology

Title: Deadly in a drop!

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

Posted: 8/17/2017 by Kathy Prybys, DO (Emailed: 8/31/2017) (Updated: 8/31/2017)
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  • 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
  • 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: Idarucizumab for Dabigatran reversal 2.0

Keywords: dabigatran reversal, Idarucizumab (PubMed Search)

Posted: 8/25/2017 by Hong Kim, MD, MPH
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Full cohort analysis idarucizumab for dabigatran associated bleeding was recently published in NEJM.

This study evaluated the laboratory correction of elevated ecarin clotting time or diluted thrombin time induced by dabigatran and time to either cessation of bleeding (Group A: patients with GI bleeding, traumatic bleeding, or ICH) or time to surgery (Group B: patients requiring surgical intervention within 8 hours).


Group A (n=301): Median time to the cessation of bleeding was 2.5 hours in 134 patients.


  • Bleeding cessation could not be determined in 67 patients
  • Cessation of bleeding could not be assess in 98 patients with ICH
  • Bleeding stopped spontaneously in 2 patients.

Group B (n=202): Median time to intended surgery after infusion of idarucizumab was 1.6 hours.

  • Normal hemostasis in 184 patients (93.4%), mildly abnormal in 10, and moderately abnormal in 3.
  • Many received PRBC and other blood products during surgery

Laboratory markers:

100% reversal of abnormal ecarin clotting time or diluted thrombin time within 4 hours after the administration


  • 5 Day: Group A: 6.3% vs. Group B: 12.6%
  • 30 Day: Group A: 13.5% vs. Group B: 12.6%
  • 90 Day: Group A: 18.8% vs. Group B: 18.9%



Authors concluded thate idaurcizumab is an "effective" reversal agent for dabigatran.

Overall, the findings are more promising compared to the interim analysis that was published in 2015.


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Category: Toxicology

Title: Importance of hemodialysis in intubated salicylate poisoned patients

Keywords: salicylate poisoning, endotracheal intubation, hemodialysis (PubMed Search)

Posted: 7/27/2017 by Hong Kim, MD, MPH
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Patients with severe salicylate poisoning may require endotracheal intubation due to fatigue from hyperventilation or mental status change.

A previously published study (Stolbach et al. 2008) showed that mechanical ventilation increases the risk of acidemia and clinical deterioration.

A small retrospective study investigated the impact of hemodialysis (HD) in intubated patients with salicylate poisoning.



53 cases with overall survival rate of 73.2%

In patients with salicylate level > 50 mg/dL

  • No HD: 56% survival (14/25)
  • HD: 83.9% survival (0/9)

If salicylate level > 80 mg/dL

  • No HD: 0% survival (26/31)
  • HD: 83.3% survival (15/18)

Bottom Line:

There is moratality benefit of HD in intubated salicylate-poisoned patient.

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Category: Toxicology

Title: Vaginal Detox?

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

Posted: 7/20/2017 by Kathy Prybys, DO (Emailed: 7/21/2017) (Updated: 7/21/2017)
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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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Hydrogen peroxide (H2O2) is a common household liquid that is used for wound irrigation/antiseptic and cosmetic purposes. The concentration of household product is 3% to 5% and is considered to be relatively safe except in large volume ingestion.

High-concentration H2O2 (>10%) is commercially available as “food grade” (35%) that is diluted for household use or for alternative medicine therapy (i.e. hyperoxygenation).

Ingestion of high-concentration of H2O2 can result in caustic injury as well as ischemic injury from gas embolism.

Ingestion of 1 mL of 3% H2O2 produces 10 mL of O2 gas while 1 mL of 35% H2O2 produces 115 mL of O2 gas.

Common symptoms/findings of H2O2 ingestions includes:

  • Nausea/vomiting
  • Abdominal pain due to gas in portal venous system
  • Caustic injury of GI track (ingestion of > 10% H2O2)
  • Arterialization of O2 gas result in end-organ injury (e.g. CVA)

A retrospective review of  >10% H2O2 ingestion from National Poison Data System showed:

  • 13.9% developed gas embolic event
  • 6.8% experienced permanent disability, including 5 deaths.


  • Minor symptoms: primary supportive
  • CT ABD/Pelvis should be considerd if abdominal pain is present
  • If significant gas is present in portal vein or evidence of end-organ injury (i.e. CVA), HBO therapy is recommended (limited evidence).
  • Endoscopy should be considered in concentrated H2O2 ingestion to evaluate for caustic injury.

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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, DO (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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