UMEM Educational Pearls - By Katherine Prybys

Category: Toxicology

Title: Super Potent Opioid Street Drugs

Keywords: Fentanyl, W-18, Clandestine (PubMed Search)

Posted: 3/4/2016 by Katherine Prybys, MD
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Pure opioid agonists such as Morphine, Hydromorphone, and Fentanyl stimulate opioid receptors and are the most potent analgesics. Fentanyl and fentanyl analogues are up to 100 times more powerful than morphine and 30-50 times more powerful than heroin.

  • Fentanyl abuse is causing significant problems worldwide. In the U.S., age-adjusted rate of death involving Fentanyl has increased 80% in 2014.
  • Sources include production in illicit clandestine labs or diversion from legitimate pharmaceutical sales.
  • 12 different analogues of Fentanyl have been identified in the U.S. drug traffic market.
  • Commonly laced in heroin or cocaine or sold as fake Oxycodone or OxyContin tablets.

W-18 is a highly potent opioid agonist with a distinctive chemical structure which is not closely related to older established families of opioid drugs. While Fentanyl is approximately 100 times more powerful than Morphine, W-18 is about 100 times more powerful than Fentanyl.

  • First discovered at the University of Alberta in 1982 in hopes of producing a non-addictive analgesic, 32 compound series named from W-1 to W-32, with W-18 being the most potent.
  • Recently emerged on the streets of Canada when police in Calgary confiscated 110 green pills being sold as Fentanyl, known on the streets as "shady eighties" or "green beans pills" but chemical analysis revealed some pills containing W-18 instead.
  • W-18 has never been used clinically as drug companies did not pick the patent, which lapsed by 1992 so little clinical experience.
  • The effects of naloxone to reverse this synthetic opioid are unknown and higher doses are expected to to be required.
  • Illicit drug manufacturers research pharmacological history in search of the more powerful, exotic, and new opioids to circumvent current legal regulations.

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Category: Toxicology

Title: Activated Charcoal, Is it still useful?

Keywords: Activated Charcoal, Gastric decontamination, Antidote (PubMed Search)

Posted: 2/4/2016 by Katherine Prybys, MD
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Throughout medical history one of the basic tenets of poisoning therapy is to remove the poison from the patient. For hundreds of years, gastric decontamination has been the cornerstone treatment for acute poisonings by ingestion. This commonsense approach endeavors to remove as much of the the ingested toxin as possible before systemic absorption and organ toxicity occurs. Multiple GI decontamination methods have been utilized including gastric emptying by lavage and ipecac, toxin binding by activated charcoal, and increasing GI transit time with cathartics and bowel irrigation. Numerous studies have been conducted to assess the effectiveness of GI decontamination including measurement of amount of toxin removed by gastric retrieval, reduction of bioavailability by measuring blood levels, and finally comparison of clinical outcomes of patients treated with and without GI decontamination. Controlled studies have failed to show conclusive evidence of benefit and have even demonstrated resultant harm especially with use of gastric lavage. Activated charcoal has a tremendous surface area capable of binding many substances. Although viewed as relatively safe it does have risks in certain subsets of patients, pulmonary aspiration the most common, and is no longer routinely recommended.

Considerations for use of Activated charcoal (AC) use in acutely poisoned patients:

  • AC does not bind alcohols, hydrocarbons, heavy metals
  • Contraindications include diminished level of consciousness, seizure, emesis, unprotected airway, and intestinal obstruction
  • Consider AC use in cases where there is potential for toxin to remain in the gut longer such as with delayed-release formulations or slowed gastric emptying
  • Consider AC use in cases of expected severe toxicity with lack of effective antidote

The decision to use activated charcoal is no longer standard of care but should be individualized to each clinical situation weighing the risk versus clinical benefits.

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Category: Toxicology

Title: Caffeine: The socially acceptable psychoactive drug

Keywords: Caffeine, Energy drinks (PubMed Search)

Posted: 1/7/2016 by Katherine Prybys, MD (Emailed: 1/8/2016) (Updated: 1/8/2016)
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Caffeine is the most commonly used psychoactive substance in the world. It is widely available in coffee, tea, chocolate,soft drinks, OTC medicines, and energy drinks. The vast majority of people consuming caffeine appear to suffer no harm while enjoying it's stimulating effects. This has led to the widely held perspective that caffeine is a completely benign substance with no adverse health effects exists.

Although, children and adolescents are at particular risk, many caffeine containing products are specifically marketed at them. Alarmingly, statistics demonstrate that caffeine intake among children and adolescents has increased by 70% in the last 30 years. Energy drinks are of special concern as they represent the fastest growing component of the beverage industry, contain significant quantities of caffeine as well as high levels of sugar, and can place children at high risk for caffeine intoxication.

There are many negative health consequences documented with caffeine use which occur in a dose dependent manner with individuals differing in their susceptibility to caffeine-related adverse effects:

Acute Toxicity:
  • Arrhythmias
  • Anxiety
  • Agitation
  • Seizure
  • Nausea,vomiting, diarrhea
  • Diuresis
  • Metabolic disturbances
  • Hypotension
  • Rare fatalities

Chronic Effects:

  • Insomia
  • Palpitations
  • Headaches
  • Diuresis
  • Gastric acid secretion
  • Urinary incontinence in women
  • Adverse effect on wound healing process, the aging process of the human skin
  • Low birth weight babies
  • Withdrawal state
  • Increased risk of cardiovascular events (heart attack,strokes, peripheral artery disease and kidney failure) in young adults with mild hypertension.

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Carbon monoxide (CO) is a colorless, odorless, tasteless toxic gas produced by incomplete combustion in fuel-burning devices and is a leading cause of poisoning morbidity and mortality.

Symptoms can be easily misinterpreted (e.g., headache, nausea, dizziness, or confusion) thus victims may not realize they are being poisoned.

CO detectors use an audible alarm and are effective in alerting potential victims of presence of CO. Some versions offer a digital readout of the CO concentration. Detectors are not a simple alarm level (as in smoke detectors) but are a concentration-time function.

In the UL 2034 Standard, Underwriters Laboratories specifies response times for CO alarms:

  • 70 ppm sounds alarm within 60-240 minutes
  • 150 ppm sounds alarm within 10-50 minutes.
  • 400 ppm: sounds alarm within 4-15 minutes.

Current Occupational Safety and Health Administration permissible exposure limit for CO is 50 parts per million as an 8-hour time-weighted average concentration.

CO detectors have a limited lifespan of up to 7 years.

Forty percent of residential detectors studied failed to alarm in hazardous concentrations, despite outward indications that they were operating as intended.

CO detectors 10 years and older had the highest failure rates.

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Category: Toxicology

Title: Designer drugs & Synthetic Marijuana: Hijacking of chemical research for no good!

Keywords: THC, Spice, JWH (PubMed Search)

Posted: 11/5/2015 by Katherine Prybys, MD (Emailed: 11/6/2015) (Updated: 11/6/2015)
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Designer drugs are structural or functional analogs of controlled substances produced to mimic pharmacological effects of the original compound while circumventing legal restrictions and detection on drug screens. Considered "legal highs" by the public, these highly potent drugs are produced in clandestine laboratories with no regulations for quality control or clinical testing for phamacological effects and thus present major threat to public health. Examples include synthetic hallucinogens (DOM: STP), opiates ( methylfentanyl:china white), stimulants (methamphetamine:crank, MDMA: ecstasy, cathinones:bath salts) and synthetic cannabinoids (spice).

The synthetic cannabinoids are the newest designer drugs and numerous cases of intoxication are being reported including some fatalties.Cannabinoids fall into 3 classes: endocannabinoids, phytocannabinoids, synthetic. Marijuana, the best known cannabinoid is plant derived and its psychoactive effects are mainly due to delta-9-tetrahydrocannabinol (THC) which binds with the endocannabinoid receptors CB1 and CB2 found throughout the central and peripheral nervous system and peripheral organs. The CB receptors interact with opiate receptors which is likely responsible for the analgesic effect.

Since 1984, the John Huffman research group at Clemenson University synthesized over 450 cannabinoid compounds for biomedical reseach known as "JWH compounds". These compounds hold great promise in the investigation of multiple diseases and development of new novel therapies. Over the last several years, these cannabinoid compounds began cropping up sprayed onto herbs marketed in colorful packets and sold on the internet, convienence stores, and head shops. Although clearly labeled as "not for human consumption" considered on the street as a legal alternative to marijuana.

Key Points:

  • Common names: Spice, K2, Smoke, Skunk, Purple Haze, Scooby snax, Crazy Monkey.
  • JWH 018 (4-5 fold greater affinity for CB receptor than THC), JWH 081,122, 210
  • Exact composition of products unknown and ever changing to avoid legal restrictions.
  • Cannabinoid dose can vary greatly between products and even within same package "hot spots" are found where the drug is more concentrated.
  • Often shown to be contaminated with impurities like beta agonists clenbulterol
  • No clinical human studies on effects or any routine detection assays available.
  • Clinical effects can vary from commonly described anxiety agitation, tachycardia to sedation and somulence.

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The majority of prescriptions used for the treatment of nausea and vomiting in pregnancy (NVP) in the United States have been with medications not labeled for and not classified as safe in use during pregnancy by the Food and Drug Administration. Over the last decade, the extremely potent 5HT3 receptor antagonist, Ondansetron (Zofran) has been increasingly used for NVP. However, the FDA has cautioned against its use in pregnancy based on recent studies regarding the association between Zofran use in early pregnancy and congenital cardiac malformations and oral clefts (cleft lip and palate). In addition, Zofran poses maternal risk of arrhythmias from possible QT interval prolongation which can result in the potentially fatal arrhythmia (Torsades de pointes) and Serotonin syndrome. The American College of Obstetricians and Gynecologists (ACOG) has issued new guidelines for the diagnosis and management of NVP. A safe and effective category A drug is available in the U.S., Diclegis (doxylamine succinate and Vitamin B6, pyridoxine hydrochloride) which has been studied in hundreds of thousands of pregnant women. Unisom SleepTabs (Sanofi Aventis; oral vitamin B6 and doxylamine), which are available OTC in the U.S., have been studied in more than 6000 patients and control participants, with no evidence of teratogenicity. In randomized trials, this combination has been associated with a 70% reduction in nausea and vomiting. ACOG therefore recommends this combination as first-line therapy for NVP. Following treatment failure with dietary modifications and alternative therapy remedies such as ginger capsules (250 mg qid) and acupuncture, pharmacologic therapies should include: 1. Vitamin B6 (pyridoxine), 10 to 25 mg every 8 hours, and doxylamine, 25 mg at bedtime and 12.5 mg each in the morning and afternoon. 2. If parental antiemetics are required, phenothiazides such as prochlorperazine or promethazine or Ondansetron in refractory cases. 3. Prokinetic agent Metoclopramide (Reglan; tablets, Alaven; injection, Baxter) is a dopamine antagonist. The FDA has issued a black-box warning concerning the use of Reglan in general. Because the risk for exrapyramidal complications, tardive dyskinesia increases with the duration of treatment and the total cumulative dose, treatment duration should not exceed 12 weeks. 4. Intravenous fluid replacement with multivitamins, especially thiamine is indicated with use of dextrose containing solutions (to prevent Wernicke's encephalopathy) until ketosis resolves.

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Poison ivy, oak, and sumac (Toxicodendron sp) causes a highly puritic, allergic contact dermatitits (ACD) that affects between 10 and 50 million in the US every year. It is a significant occupational hazard as well a scourge for outdoor enthusiasts.

Toxicodendron species contain oleoresins, known as Urushiol compound, secreted by all parts of the plant. Contact with the oil usually occurs by brushing against or direct handling of the plant or contaminated items. This toxin triggers a type IV delayed hypersensitivity reaction in approximately 75% of the population. Within 12-24 hours an erythematous, often linear, vesicular rash develops but new lesions can occur up to 2 weeks later.

There is no ideal treatment for ACD induced by Toxicodendron species. Avoidance and barrier protection are the best strategies. Recommended medications include antihistamines, topical preparations, and systemic steroids. However, steroids require a 2-3 week course to prevent recrudescence of the rash and are not without undesirable side affects.

Zanfel, an OTC granular polyethlene paste, removes urushiol by binding with it to create an aggregate cluster that can be washed away with water. It is highly effective, providing rapid relief even as a sole agent but requires multiple initial applications and is expensive. Mean Green hand scrub has similar ingredients and is claimed to bond urushiol also. Excessive scrathing and abrasive scrubs can cause secondary cellulitis requiring antibiotics.

Category: Toxicology

Title: Spider bite

Posted: 9/5/2019 by Katherine Prybys, MD (Emailed: 6/24/2024) (Updated: 6/24/2024)
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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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