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It's Over the Counter So It Must Be Safe Nancy Denke DNP, ACNP-BC

It's Over the Counter So It Must Be Safe Nancy Denke DNP, ACNP-BC

It’s Over the Counter So It Must Be Safe Pre 7 Nancy Denke DNP, ACNP-BC, FNP-BC, FAEN

Disclosures It's Over the Counter So It • Nancy Denke DNP, ACNP-BC, FNP-BC, Must Be Safe FAEN has no financial relationships with commercial interests to disclose • Any unlabeled/unapproved uses of or products referenced will be disclosed

Nancy Denke DNP, ACNP-BC, FNP-BC, FAEN

Objectives Introduction • Discuss the general approach to the "poisoned" OTC overexposure is common in patient the U.S. due to ease of availability and lack of • Evaluate the risks, benefits, and safe use of provider oversight common • Explain reasons for patient-related medication errors, strategies to prevent overdose, symptoms of overdose, and strategies to treat acute

Prompt recognition & tx may prevent morbidity/mortality R/T analgesic OD

The Approach to the Ingestion Patient • Patients with problems are common in general medical practices • No age or socioeconomic group is not touched • Initial dx & tx of addiction problems are often done by the PCP before referral • You can be a powerful influence for getting a patient to accept tx, especially when you Gummin D.D., et. al. (2018). 2017 Annual report of the American association of are empathic without being judgmental poison control centers’ National Poison data system (NPDS): 35th annual report. Clinical Toxicology, 56(12), 1-200.

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Sedative Intoxication Clinical PEARLS Physical Symptoms Psychiatric Symptoms Slurred speech Inappropriate Behavior

Incoordination Mood Liability

Unsteady Gait Impaired Judgement

Nystagmus Impaired Social Functioning

Decreased Reflexes Impaired Occupational Functioning Impaired Attention or Memory

Stupor or Coma

Symptom Intoxication Withdrawal Cardiac- Heart Rate Tachy, CP, arrhythmias Normal BP Normal or increased Normal Temp Chills/hot flashes Normal GI/Wt N & V, weight loss Increased appetite Psychomotor Agitation Decreased Muscular Weakness Normal

Neurological Seizure Vivid dreams, hypersomnia Affect Euphoric to blunted Fatigued

Vigilance Hyper Normal

Emotion Irritable, angry Dysphoric

Reaction to others Sensitive, paranoid Normal

Judgement Impaired Normal for the patient

Social Impaired Normal for the patient

Now Lets Talk About What Can You Can By at Your Local Pharmacy or “Drugstore”

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Why Buy When You It Affects the CNS Can Get This!!! • Might stagger when they walk, speak The vanilla extract without making sense, or seem sleepy is usually 35 • They might vomit because alcohol can percent or 70 proof. irritate the stomach • Breathing and HR might decrease, along Vodka is usually 70 with BP or 80 percent proof

It’s Everywhere!! Tylenol Extended Release

=

Tylenol Emergency Room

APAP Fun Facts! Pharmacokinetics • #1 for overdoses in the world! Absorption • Found in >600 different Rx and OTC med, • Rapidly absorbed from the GI tract including: • Peak concentration occurs between 60 -120 min – pain relievers, reducers, sleep aids • Peak plasma levels occur within 4 hours cough, cold, and allergy medicines Metabolism • Listed in ingredients as acetaminophen, • Occurs via several pathways in the liver APAP or actem! Excreted by the kidneys • Max dose 4000 mg/day Half Life • Acetaminophen Awareness Coalition- •2 hr https://www.knowyourdose.org/common- • With liver dysfunction, may ↑to 17 hr medicines/

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How Do I Know If My Patient Rumack-Matthew Nomogram Took a Toxic Dose? Factors involved in predicting hepatotoxicity • total quantity ingested • time from ingestion to treatment 150 mg/dl at • age of the patient hihours is • alcoholism 4 possibly toxic • enzyme inducing medications

 Serum concentration related to Rumack nomogram • Adult threshold for liver damage is 150 mg/kg • Children under 10 appear to be more resistant

When to Treat? Why NAC (Acetadote)?

90% to 95% of acetaminophen metabolism takes place in the liver

Acetaminophen Case Study The Labs

• MR is a 21 yo female with chronic abdominal pain due to gastroparesis. • Recently she began having increases pain dtthldue to the placemen tfGtb5t of a G tube 5 week s ago • To deal with the pain she has taken 120 tabs of Percocet • 4 infusions of NAC

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Treatment Treatment 4 hour post-ingestion level- one time only! 4 hour post ingestion APAP level • levels drawn earlier may be erroneous • levels may be accurate out to 18 hours • levels drawn earlier may be • Labs erroneous – Baseline CBC • levels may be accurate out to 18 – Creatinine, BUN, blood sugar, electrolytes hours – PT/INR, AST, ALT • elevations typically seen 24-36 hrs post ingestion

N-acetylcysteine APAP Summary Lovingly known as NAC • APAP may overwhelm the livers stores of • If APAP level plots above the possible risk glutathione. line administer N-acetylcysteine (NAC) • Rise in liver enzymes may occur, which reflects • If NAC is indicated, full regimen should be the hepatic toxicity followed • Timely administration of NAC may protect the – 2 or 3 bag infusion patient from hepatic damage • NAC loading dose is 140 mg/kg • Therapy should be initiated as soon as possible, but NAC is beneficial at any time • NAC maintenance doses are 70 mg/kg • If APAP levels can not be obtained, assume a toxic dose has been ingested, initiate NAC, and continue until regimen complete

What Should I Remember? • APAP present in polypharmacy ingestions – OTC meds to treat insomnia, allergic disease, & cold symptoms. – Consequential risk of unintended diph enh yd rami ne OD i n child ren • No symptoms may be present…screen • 150 mcg/ml at 4 hours is a “treat” level • Metoclopramide (Reglan) 0.1-1.0 mg/kg is very effective in controlling nausea/vomiting associated with APAP toxicity

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Hooked on Benadryl Can Diphenhydramine be Abused? • More than a harmless dependency • Usually not, BUT if you quit you may have – Some use as an OTC sleep aid, while others some adverse symptoms if enjoy the sedative & euphoric effects it diphenhydramine has not been taken at provides as a result of dopamine release the usual recommended dose • It’s li n ke d to s hor t-tlterm memory loss. • If t ak en fldidftitfor a prolonged period of time at a • It’s an larger than usual dose, there may be some symptoms of withdrawal including insomnia, irritability, picking even severe confusion

Symptoms of Benadryl Diphenhydramine Case Study Withdrawal • 17 yo guy • May not be as bad as ETOH or , but • Ingested entire bottle (40 tabs) Benadryl™ they are very real and need to be monitored (diphenhydramine) 50 mg • Symptoms of withdrawal include: • Mom found him acting strangely (agitated, – IidtlInsomnia and restlessness confused, with jerking and picking – Nausea and diarrhea movements) ≈ 2 hrs later & called EMS – Hot and cold sweats • No co-ingestants – Cold-like symptoms • Displaying typical anticholinergic S & S • ECG shows wide-complex tachycardia & just had a Sz

Anticholinergic Initial Symptoms • Use of has a long hx which includes ritual, recreational & therapeutic use of Blind as a bat (dilated pupils) containing , and Dry as a bone

• Antagonist of the histamine H1 receptor with Full as a flask (can’t urinate) anticholinergic properties Hot as a hare (or hell, or Hades) • Classic anticholinergic syndrome is a Red as a beet manifestation of competitive antagonism of Mad as a hatter (easily describable, ) acetylcholine at peripheral and central muscarinic receptors Tacky (tachycardic) as a leisure suit – Systems affected Phantom behaviors (“woolgathering”- “picking”) • CNS, & the Autonomic Nervous System (parasympathetic portion)

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Diphenhydramine-Induced Progression of Symptoms Symptoms & Treatment Initial peripheral parasympathetic signs and • Rhabdomyolysis symptoms (“blind as a bat, . . .”) Then confusion with hallucinations and agitated •Sz delirium – benzodiazepines • MtbliMetabolic ac idiidosis – Sodium bicarb • Toxic Psychosis – ID can be difficult since its presents as delirium Eventually stupor and coma • Physostigmine Finally recovery of consciousness with paranoia

Dextromethorphan (DXM) Things to Do! Popular Street Names • Obtain an ECG (to rule out prolonged • Purple drank QTc) • • Administer benzodiazepines (for sz or • Sizzurp agitation) • DblDouble cup • Consider physostigmine (for altered • Skittles mental status) • Orange crush • Obtain APAP level •Dex • Consult toxicologist • Red devils •Velvet

DXM • 1/10 teens has used DXM to get high – also known as “robotripping” • effects prompt some teens to use it for anxiety- get a powerful buzz – dose for dissociative effect is around 1000mg or about 500mL of cough syrup • Many mix with ETOH or weed or to intensify the effect

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3977765/?report=printable

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Serotonin Syndrome • can act as a non- selective serotonin reuptake inhibitor • Important to recognize serotonin syndrome so you avoid adding another serotoninergic agent such as ondt(Zf)!dansetron (Zofran)! • Hallmark of serotonin syndrome is clonus • Treatment – Cool them – IV fluids and benzodiazepines

Triple C One Teens Thoughts • Coricidin® products have high prevalence of abuse in the adolescents “After the first time I did it I just really loved – Dextromethorphan & chlorpheniramine maleate it. I would take them when I got up in the morning, before school, during school, after • Poor man’s PCP school, before I went to bed. I hallucinated a • The street terms for illicit use are skittling lot. It was kind of like I was in a dream or and robo-tripping something, like so disassociated. I liked that feeling of not being in reality. And I just kept using it after that.”

Toxic Effects • It is a strong non-competitive N-methyl-D- aspartate (NMDA) receptor antagonist. When it binds to and blocks these recepppptors, it can produce , hyperactivity, and psychosis • Serotonin syndrome a likely result of abusing the drug https://www.ashwoodrecovery.com/bl – sharp ↑ in HR, diaphoresis, extreme anxiety, og/addicted-triple-c-means-life/ hyperthermia

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Case • 17 yo found at Albertson’s exhibiting bizarre Things to Remember behavior after he had stolen & rapidly ingested • Dextromethorphan at high doses acts as a about 30 tablets of Coricidin HBP “to get high” dissociative general and • ED: tremulous, diaphoretic demonstrating a similar to and clouded sensorium, euphoric mood, & paranoid thought process (PCP) by antagonizing the NMDA receptor in a dose dependent • He stated that he could “look at people and know exactly what they were thinking” manner – VS : 187/112, 116, 16, 98.9, 100% RA • Appealing to teens as they are easily – Awake with eyes open but slowly responsive available (OTC), legal, inexpensive, and –GCS was 12 – Pupils were dilated and slowly reactive preceived as safe – The rest of the exam was essentially negative

Imodium (Lope Dope!) Treatment Plan Or Poor Man’s Methadone • Dextromethorphan not detected by basic drug • Loperamide a common OTC anti-diarrheal screens and should be considered when – Considered safe 2-16 mg daily- need to take very evaluating patients with a dissociative toxidrome large amounts, 50-100 2 mg caps to get high • Always get a Acetaminophen levels !!!!! – Within these levels, rapid metabolism & poor – Consider liver panel and INR blood-brain barrier penetration • No specific antidote exists for dextromethorphan – Active ingredients: diphenoxylate (similar to toxicity- symptomatic care! Demerol) and atropine (anti-cholinergic) • Benzodiazepines should be administered for • Potent mu- receptor agonist & seizures and aggressive cooling measures for anticholinergic agent hyperthermia • Poison control centers reported that overdoses doubled between 2009 and 2015

Loperamide Will Stop You Up Drug Abusers Are Very Smart! But It Can Also Bring You • Discover effects accidentally Down!!! • Institute for Safe Medication Practices notes- • Hard to believe that people will chug down – “Imodium is actually an opioid & 40-50x more potent than in the gut” 30- 40 pills to get high – Former heroin addict was taking 60-100 Lomotil pills with alcohol to achieve euphoria “People figured out that if they took loperamide in high amounts, or in combination with • Ingestion of higher (> 50 mg) associated medicines that alter the stomach’s [acidity], it with euphoria, CNS depression, & can be absorbed more systemically across the cardiotoxicity barriers and act on opioid receptors” Carla Marienfeld, MD

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Signs & Symptoms A Quick Look at Supplements • Urinary retention • Ileus • The worldwide market for herbal and dietary supplements is booming. • Extreme dehydration due to severe N & V and diarrhea • Over ½ adults in the US report consuming dietary supplements • Liver dfdysfuncti on • US FDA has warned of numerous dietary • Cardiac conduction abnormalities/events supplements containing undeclared, • Depressed CNS & respiratory dysfunction unapproved pharmaceutical ingredients & • Stupor is responsible for eliminating potentially • Lack of coordination hazardous dietary supplements from the • Seizures marketplace

JAMA Pediatr. 2016;170(9) doi:10.1001/jamapediatrics.2016.0971

Acute Toxicity Some Quick Thoughts

• Tachycardia and neuroexcitation were most likely symptoms following inhalation • Edibles most common products to cause symptoms in all age groups • TX- treat the symptoms!

10 It’s Over the Counter So It Must Be Safe Pre 7 Nancy Denke DNP, ACNP-BC, FNP-BC, FAEN

Herbs with Anticholinergic Even More Effects • Plants with anticholinergic activity include: – stramonium (jimson weed) – A belladonna (deadly nightshade) – HiHyoscyamus niger (hen ) – Ginseng may be contaminated with (scopolamine-containing mandrake) produced anticholinergic toxicity. • St. John's wort (Hypericum perforatum) weak MAOI and serotonin agonist

CV Effects Hepatotoxic • Ephedra and ephedrine-containing • Kava-kava (Piper methysticum)- hepatoxic products (eg, Ma Huang) may produce: • Mentha pulegium (ie, pennyroyal oil, – cardiac stimulation, HTN, peripheral "squaw" mint) teas have been mistaken for vasoconstriction, MI, & intracerebral other mint teas hhhemorrhage • Sho-saiko-to (a mixture of 7 herbs), a Rx • FDA to ban ephedra products for use in med in Japan, for tx of hepatitis weight loss. However, ephedra is available • Kombucha tea. Case reports describe a for sale as an asthma preparation and syndrome characterized by hepatotoxicity, should still be considered for abuse. It is pulmonary edema, & DIC after ingestion. still promoted in body-building circles.

Hematologic System Other Things • Licorice root may cause renal K+ loss • Ginkgo biloba reported to ↑ bleeding times • Echinacea & chamomile tea can cause & may contributed to ICH anaphylaxis • Yohimbine use associated with • Royal jelly & yohimbine can cause allergic agranulocytosis reactions • Shiitake mushrooms can cause severe dermatitis • Garlic, chamomile tea, and capsicum may produce contact dermatitis

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Contamination Herbal Assault: • Chinese herbal medications have been an Liver Toxicity of Herbal and incredible source of contamination Dietary Supplements – Find high concentrations of heavy metals: Lancet Gastroenterol Hepatol. 2018 Mar;3(3):141 • Lead, mercury , and arsenic (also found in kelp) • ppp With mounting evidence of the health risks associated with herbal and dietary supplements, it is clear that increased awareness and education—among both physicians and patients—is essential

Can Apricot Seeds Treat Cancer? • An apricot kernel is a single seed found inside the apricot stone & promoted as a Apricot seeds and Kernels “superfood” supplement for many different types of CA • Inhabitants of the North-West Himalayas believe wild apricots & their kernels have both nutritional & medicinal uses • Amygdalin, found in apricot kernels, may be a way to eradicate tumors and prevent cancer by stopping cells from reproducing

Case What is Amygdalin? • BB stood in the doorway of MG’s room, munching • Also called Laetrile and Vitamin B 17 away on something as they discussed the day • Amygdaline is not only found in the stone • “Those better not be almonds,” MG said. “You know of an apricot, it can also be found in the I’m allergic to those” seeds of such fruits as: • “No, no,” BB replied, “I would never do that. These are apricot pits.” – apples, cherries, plums, & peaches • “What?!? Don’t eat those! They’re poisonous!” • Amygdalin is a cyanogenic glycoside • BB pooh-poohed the warning, arguing the kernels • That means when someone eats were organic and he’d bought them at the health amygdalin, it is converted to CYANIDE food store. • “Look! It’s the superseed of the Hunza people, with Vitamin B17!”

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Highly Dangerous Appeal of Read the Ingredients Eating Apricot Kernels • Then he turned the bag over and read the • This is the story of an Australian man fine print. His face went grey: • A seemingly well 67-yo man” in a 15-minute routine procedure, suddenly experienced severe “Caution: Do not consume more than 2-3 hypoxia kernels per day. Keep out of the reach of • Battery of tests done to find the case & all WNL children. Pregnant and nursing women • His level of cyanide was 1.6 mg/L should not consume apricot kernels. • In interview, he revealed he consumed apricot Health Canada warns that eating too kernels Q day for the past 5 yr many apricot kernels can lead to acute – His self-medication routine-3 tablets of a commercially manufactured kernel product cyanide poisoning.” – 2 teaspoons of a homemade preparation

Did You Say Cyanide? •HA •N & V • Abdominal cramps • Dizziness & weakness • Altered Mental Status • Seizures • CV effects and cardiac arrest • Respiratory difficulties • Coma & death

So How Much He Consuming? What to Remember • Overall, he was consuming 17 mg cyanide “Physicians should be aware that self- per day prescription with complementary medicines • 0.5-3.5 mg/kg of cyanide can be lethal!!!! can result in potentially harmful , • Exposure can lead to long-term neuro and and mayyy be more common that currently CV effects understood” • Rules restricting the promotion of unproven health claims for non-medical Alex Konstantatos MD products in many countries mean that kernel products are often sold simply as general tonics to aid health and digestion

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References • Gummin D.D., Mowry J.B., Spyker D.A., Brooks D.E., Osterthaler K.M. & Banner W. (2018). 2017 Annual report of the American association of poison control centers’ National Poison data system (NPDS): 35th annual report. Clinical Toxicology, 56(12), 1-200. • Konstantatos A., Shiv Kumar M., Burrell A. & Smith J. (2017). An Thank You unusual presentation of chronic cyanide toxicity from self-prescribed apricot kernel extract. BMJ Case Reports. doi: 10.1136/bcr-2017- 220740 • Noble M.J., Hedberg K., & Hendrickson R.G. (2019). Acute cannibals toxicity. Clinical Toxicology, 24,1-8 • Teschke R, Zhang L, Long H, Schwarzenboeck A, Schmidt-Taenzer W, Genthner A, et al. (2015). Traditional chinese medicine and herbal hepatotoxicity: A tabular compilation of reported cases. Ann Hepatol, 14 (1),7-19

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