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Melissa Ruble, Pharm.D., BCPS Assistant Professor University of South Florida College of Pharmacy

http://fluoridedetective.com/wp-content/uploads/2011/07/Doctor-Patient.jpg

I have nothing to disclose

Upon completion of this program, pharmacists will be able to

Analyze the six basic steps to approaching a poisoned patient Classify toxidromes using clinical signs and symptoms Demonstrate an understanding of common xenobiotics and their antidotes Formulate treatment plans for common overdose patients Describe common clinical presentations and treatment strategies of bites and envenomation including snakes and spiders

Upon completion of this program, pharmacy technicians will be able to

Identify the six basic steps to approaching a poisoned patient Classify toxidromes using clinical signs and symptoms Demonstrate an understanding of common xenobiotics and their antidotes Describe common clinical presentations and treatment strategies of bites and envenomation including snakes and spiders

BM is a 33 yo male who is found wandering the streets chasing a man he says owes him money. He appears altered and anxious. He is profusely sweating and yelling for a man named “Skinny” Pete. The police apprehend him and find blue methamphetamine in his pocket. As the police question him he begins to complain of chest pain and falls to the ground unresponsive. EMS is called immediately and he is brought emergently into your ED. What are the next steps in ensuring BM is treated appropriately?

1.Stabilization 2.Patient evaluation/diagnosis 3.Decontamination 4.Antidotes 5.Elimination enhancement 6.Continuous care/disposition

Brief examination to identify necessary measurements in preventing further deterioration of the patient CAB

Circulation/compressions Airway Breathing

Altered mental status Other complications

Check blood pressure, pulse rate, and rhythm If no pulse start CPR – ACLS

Begin ECG monitoring Check for arrhythmias, QT prolongation, QRS prolongation

Obtain IV/IO access ICU patients require two 18 gauge

Start fluids NS is fluid of choice for adults 5% dextrose in ¼ normal saline is used in children

Check for gag reflex Glascow coma scale (GCS) less than 8 INTUBATE!

Optimize the airway position Place neck and head in the sniffing position Apply jaw thrust to force the flaccid tongue forward Head-down, left-sided position ▪Allows tongue to fall forward and secretions to drain out of

mouth Remove any obstruction or secretions by suctioning

http://medipptx.blogspot.com/2010/07/airway-management_4650.html

Respiratory failure Failure of ventilatory muscles ▪Paralysis (neuromuscular blockers, botulinum toxin, organophosphates,

snakebites, warfare nerve gases) Central depression of respiratory drive ▪Antihistamines, barbiturates, clonidine, ethanol, opioids, TCAs Severe pneumonia/pulmonary edema Obtain arterial blood gases (ABG) ▪Estimate the adequacy of ventilation from pCO2 levels

▪> 60 mm Hg indicates a need for assisted ventilation Hypoxia/Hypercarbia

Brain damage, cardiac arrest, acidosis, dysrhythmias Administer supplemental oxygen as indicated ▪Consider hyperbaric oxygen (carbon monoxide poisoning)

Bronchospasms Administer supplemental oxygen as indicated

AMS can be accompanied by respiratory depression and thus airway is evaluated prior to CNS changes Maintain airway and assist ventilation when necessary Naloxone administration

All patients with respiratory depression should receive naloxone

Check blood sugar EMS and immediate bedside glucose determination Administer concentrated glucose if necessary ▪Adults 50% dextrose – 25g IV ▪Children 25% dextrose – 2 mL/kg IV

Check body (rectal) temperature If head trauma obtain CT scan If suspected meningitis or encephalitis, perform lumbar puncture Treat seizures

Benzodiazepines Control agitation

Sedatives (benzodiazepines, atypical antipsychotics)

Rhabdomyolysis Muscle cell necrosis is a common complication of poisoning Aggressively hydrate patient Alkalinize the urine by adding sodium bicarbonate to fluids Provide hemodialysis if needed

Allergy Dystonia/rigidity

Check for track marks, trauma

History Detailed physical examination Laboratory tests Toxin identification

Toxidrome

Frequently unreliable or incomplete Multiple xenobiotics

Ask patient what they took, how many, time of ingestion Ask family, friends, EMS about medications known to be used by the patient or found at the scene If information is available, call patient’s pharmacy to determine whether other prescription medications may have been taken

EFORCE

Autonomic physical examination Blood pressure Pulse rate Pupils ▪Size ▪Nystagmus Skin ▪Diaphoresis, pale, cyanosis Peristalsis

Neuropathy Odors

Cyanide – bitter almond Arsenic, organophospates – garlic Methyl salicylate - wintergreen

Electrolytes Serum glucose BUN/SCr LFTs CBC Urinalysis

ECG Serum acetaminophen, salicylate, and ethanol level Pregnancy test Serum osmolality Drug levels when necessary – phenytoin, digoxin

Skin Wear protective gear and wash exposed areas promptly Contact regional poison center for information about the hazards of the chemicals involved Remove contaminated clothing and flush exposed areas with copious amounts of lukewarm water or saline

Eyes Flush eyes with lukewarm water or saline ▪Remove contact lenses

Inhalant Remove victim from exposure Observe for upper respiratory tract edema ▪Assist ventilation when necessary

GI Controversial ▪Little support in the medical literature for gut-emptying procedures ▪Studies have shown that after 60 minutes very little of the ingested

dose is removed by emesis or gastric lavage Activated charcoal ▪Highly adsorbent powdered material ▪Large surface area – adsorbs most toxins when given in a 10 to 1

ratio (charcoal to toxin) ▪Many times it comes mixed with sorbitol ▪Dose – 1 g/kg Whole-bowel irrigation ▪Polyethylene glycol ▪High flow rates to wash intestinal contents

Administered after identification of specific agent or signs and symptoms of agents without contraindications Naloxone is recommended in any patient who presents with CNS depression Become familiar with antidotes and dosing as this is an emergency situation

Know where to find contraindications and monitoring parameters during treatment

Supportive care Seizure precautions Vomiting

Three critical questions to ask yourself Does the patient need enhanced removal? ▪Severe or critical intoxication with deteriorating condition despite

maximal supportive care ▪Normal or usual route of elimination impaired (hepatic or renal

failure) ▪Ingestion of lethal dose or lethal blood level Is the drug or toxin accessible to be removed? ▪Volume of distribution

▪Large Vd has very low plasma concentrations and will not be removed with HD

▪Protein binding ▪High protein binding makes it difficult to remove by dialysis

Will the method work? ▪Does the removal procedure efficiently extract the toxin from the

blood?

Urinary manipulation Relies on renal clearance of medication Alkalize the urine Especially helpful for salicylate poisoning

Hemodialysis What type of medications will this work for?

Activated charcoal If overdose is known to have been less than 1 hour Increased risk of aspiration if AMS

Adequate observation Usually a 6 hour minimal observation period Close monitoring requires ICU

Poison prevention consultation Determine need for further evaluation Educate patients on prevention especially if pediatrics are involved

Psychiatric counseling Baker act if intentional

Referral for follow-up treatment Specialists – cardio, renal, psych, OB

Definition Derived from the words toxic syndrome Group of signs and symptoms that are associated with exposure to a particular substance or class of substance Described by a combination of vital signs and clinically apparent end-organ manifestations

Central Nervous System (CNS)

Mental status Ophthalmic system

Pupil size Mucous membrane

Moist vs. dry

Gastrointestinal system Peristalsis

Genitourinary Urine retention vs. incontinence

Dermatology Skin dryness vs. diaphoresis

ALWAYS remember that the actual clinical manifestations of a poisoning are variable Most useful when looking at clinical presentation and preparing a framework for assessment Incomplete toxidromes may still provide clues to correct diagnosis

Be a detective! Partial presentations DO NOT imply less-severe disease

Anticholinergics Cholinergics Ethanol or sedative hypnotics Opioids Sympathomimetics

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BP P RR T Mental Status Pupils Peristalsis Diaphoresis

-/

±

Delirium

BP P RR T Mental Status

Pupils Peristalsis Diaphoresis

± ±

-/

- Normal to depressed

±

DUMBBELLS SLUDGE


Pupils Peristalsis Diaphoresis Other

-/

Depressed agitated

±

- Hyporeflexia, ataxia


Pupils Peristalsis Diaphoresis Other

Depressed

- Hyporeflexia


Pupil size

Peristalsis Diaphoresis Other

Agitated

-/

Tremor, seizure

56 yo agitated female is brought into the ED restrained by EMS. The patient is tachycardic, with an elevated core temperature, mydriasis, and delirium. Upon further assessment you notice a decrease in peristalsis and signs of dehydration. What toxidrome are you suspecting?

JR is a 32 yo male who is brought in by his girlfriend. He is very lethargic with pin point pupils (miosis). His blood pressure is 80/40 and pulse is 50. His respiratory rate is 8 breaths/min and he is having trouble keeping his airway. Upon further evaluation you notice he has decreased peristalsis. What toxidrome are you suspecting?

NT is a 19 yo female who presents to the ED via EMS with increased blood pressure, pulse, respiratory rate, and temperature. She is very agitated and must be restrained by 4 officers. Her pupils are dilated and she is sweating profusely. What toxidrome are you suspecting?

LW is a 68 yo male who presents to the ED with is wife. She states he has been sweating more than usual all day. He has had severe diarrhea for the past several hours, salivating more than normal, urinating often, and keeps coughing up phlegm. What toxidrome are you suspecting?

A 24-year-old man with a long-standing history of drug use (cocaine, alcohol) is admitted to the ED with a suspected cocaine overdose. His BP is 210/115 mm Hg. His laboratory values are within normal limits except for SCr 2.4 mg/dL and K 5.2 mEq/L. The patient’s cardiac enzymes are normal. In addition to a benzodiazepine, which one of the following agents would be the best recommendation for this patient? Why?

A.Sodium nitroprusside B.Esmolol C.Labetalol D.Nicardipine

Case adapted from ACCP Flip Cards Pharmacotherapy

Drug overdose (OD) was the leading cause of injury death in 2012

More than doubled from 1999 to 2013 81% of drug OD deaths were unintentional

Patients unaware of max doses/combination medications

Of the 43,982 drug OD deaths in 2013, 71.3% involved opioids and 30.6% involved benzodiazepines

Centers for Disease Control and Prevention (CDC). http://www.cdc.gov/media/releases/2013/p0220_drug_overdose_deaths.html

Men were 59% more likely than women to die Whites had highest death rate

American Indians/Alaska Natives Blacks

Age 45-49 years

Centers for Disease Control and Prevention (CDC). http://www.cdc.gov/homeandrecreationalsafety/overdose/facts.html

Clinically used to treat both acute or chronic pain Available in various formulations

Epidural, inhalation, intranasal, intrathecal, oral, parenteral (SC, IV, IM), rectal, transdermal, and transmucosal

Has both euphoric and addictive potentials

Estimated that 69,000 people die from opioid overdose each year

15 million people suffer from opioid dependence Derived from opium poppy or synthetic analogues with similar effects

Examples: morphine, heroin, tramadol, oxycodone and methadone

Opioid triad Pinpoint pupils, unconsciousness, respiratory depression

World Health Organization (WHO). http://www.who.int/substance_abuse/information-sheet/en/

People with opioid dependence Especially patients following detoxicication, incarceration, cessation of treatment

People who inject opioids People taking high doses of opioids People with medical conditions such as HIV, liver or lung disease, depression

World Health Organization (WHO). http://www.who.int/substance_abuse/information-sheet/en/

Appearance White or brownish powder Black sticky substance “black tar heroin”

Physical symptoms “toxidrome” Euphoria, drowsiness (CNS depression), respiratory depression, miosis, nausea, and dry mouth

SAMHSA. http://www.samhsa.gov/atod/opioids

CAB Supportive care Antidote Labs Continuous care

Monitoring

Opioid antagonist at all receptors (U, K, D) Mechanism

Prevents action of opioid receptors Reverses effects of both endogenous and exogenous opioids Causes opioid withdrawal in opioid dependent patients

Nelson LS. Goldfrank's Toxicologic Emergencies. 10th ed. 2014. http://accesspharmacy.mhmedical.com

Dosing 0.4 – 2 mg IV Dependent patient dose: 0.04 IV Repeat every 3 minutes until improved respirations

Does the dose matter? Increased risk for acute withdrawal symptoms ▪Aspiration, pain, agitation

Goal is NOT complete arousal but to provide adequate spontaneous ventilation

ALWAYS use lowest dose initially IV NOT SC due to unpredictable onset


Long acting opioids Heroin is short acting so should not be used

Body packers Recommended dosing

2/3 initial reversal dose per hour Titrate per clinical presentation Confusing protocols


Retail (street-level) heroin always contains adulterants Historically quinine and strychnine used

Mimic bitter taste of heroin Cardiac arrhythmias

1995 – scopolamine Acute psychosis, anticholinergic crisis

2005 – Clenbuterol (B2-adrenergic agonist) Tachycardia, hypotension, hypokalemia


Inhalation of white pyrolysate Pharmacokinetics similar to IV Avoids injection drug use

Fentanyl Regional epidemics of substitution for heroin Super potent activity ▪Dramatic increase in deaths

Higher doses of naloxone may be necessary

Desomorphine 15 x more potent than morphine

Heroin substitute Less expensive Easily manufactured ▪Two-step synthetic process

Contaminated with corrosive by-products or residuals

Responsible for undesired or toxic effects

Katselou M, et al. Life Sci. 2014 May 2;102(2):81-7.

True or false Naloxone comes as a prescription for patients to administer at home that is interactive to prevent overdose in chronic opioid/high risk patients?

First synthesized as nasal decongestant Later used to treat narcolepsy

Supplied as stimulants to soldiers and prisoners of war in World War II 1980’s use increased and derivatives MDMA and MDEA were produced

“Ice” Easy to produce and low cost

Sympathomimetics – “toxidrome” Hyperadrenergic state Amphetamine > cocaine in duration of action

Acidosis Rhabdomyolysis Status epilepticus

Direct result or secondary from hyponatremia Hyperthermia – CNS alterations Intracerebral hemorrhage/cerebral infarct

CAB IV access

Sedation Benzodiazepines, propofol

Hydration and cooling Labs

CK, lactate Supportive care

Historically adulterants were inert Starches, sympathomimetic agents, local anesthetics

Levamisole Antihelminthic immunomodulator Withdrawn from market due to agranulocytosis 2009 over 69% of cocaine contained levamisole Patient presentation ▪Neutropenia, agranulocytosis, vasculitis, and purpura

JP is a 26 yo male who presents to the ED following a binge use of cocaine. He is complaining of anhedonia and lethargy. He is having trouble initiating and sustaining movement. He is cognitively intact. Is this normal and if so what is the term? Washed – out syndrome

Also known as Ecstasy, Adam, Beans, and Rolls Stimulant/Psychoactive agent Thought to be the “pure MDMA”

Infrequently found to contain MDMA Other chemicals such as methylone are also sold under this name Typically contains 1+ stimulants

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JD is a 56 yo male who has been drinking for the past few hours with his friends. As he was walking to his car to get his next case of beer, when he notices a snake on the ground. He calls his friends over and they decide to play “who can catch the snake first”. Being the competitive person he is, JD dives at the snake and grabs him by what he thought was the head. Instead he grabs the tail and ends up getting bit by the rattlesnake. His friends laugh at first but then panic and decide to bring him in to your ED. Where do you start?

VENOMOUS

Southern copperhead Cottonmouth, Water moccasin Eastern diamondback rattlesnake Timber rattlesnake Dusky pigmy Eastern coral snake

NON-VENOMOUS

Eastern rat snake, yellow rat snake Florida water snake Kingsnake Black racer

http://www.flmnh.ufl.edu/herpetology/fl-snakes/venomous-snakes

Peak number of bites in July Men comprise of 75% of cases

Children represent 10-15% Over half of reported bites occur when individual is purposefully handling the snake Herpetologists are at highest risk

Mark leading edge of swelling every 15-30 minutes Immobilize and elevate extremity Treat pain Obtain initial lab studies

PT/INR, Hgb, platelets, fibrinogen Update tetanus vaccine Contact poison control center (1-800-222-1222)

Swelling, tenderness, redness Elevated PT/INR Decreased fibrinogen or platelets Systemic signs

Hypotension, excessive bleeding, refractory vomiting, diarrhea, angioedema, neurotoxicity

BTG International Inc. http://www.supplements.annemergmed.com/PDF/Treatment-Algorithm.pdf

Establish IV access and provide fluids Mix 4 to 6 vials of crotaline Fab antivenom (CroFab®) in 250 mL NS

Infuse over 1 hour Re-examine patient for response within 1 hour

If initial control is not achieved, repeat dose of antivenom


Perform serial examinations Consider maintenance antivenom therapy Observe patient for 18 – 24 hours after initial control Labs 6 – 12 hours after initial control and prior to discharge


Do NOT administer antivenom Observe the patient for at least 8 hours Repeat labs prior to discharge If patient develops signs of envenomation, then check for indications for antivenom and proceed


Live in temperate and tropical latitudes Stone walls, crevices, wood piles, outhouses, barns, stables

Classic red hourglass-shaped marking is noted in only L. mactans

Pinprick when bitten Pair of red spots at site (uncommon)

Systemic toxicity Neuromuscular symptoms within 30 – 60 minutes Progressive pain

Sweating, contorted/grimaced face, muscle cramping, hypertension

Laboratory data is not helpful in the management Leukocytosis and CKP elevations are mostly found but do not predict outcomes

CAB Support respirations when indicated

Wound evaluation Tetanus prophylaxis

Pain management Grade 1 – cold packs/NSAIDS Grade 2 and 3 – IV opioids and benzodiazepines

Risk of anaphylaxis and serum sickness Latrodectus antivenom

Rapidly effective and curative Reserved for severe reaction and designated as a grade 3

1 to 2 vials in 50 – 100 mL 5% dextrose or 0.9% NS infused over 1 hour

Antivenoms in the works Analatro ▪Less chance of anaphylaxis

Evaluation of a poisoned patient should be thorough, systematic, and performed quickly It is important to understand the mechanisms of toxicity and recognize the signs and symptoms of presenting patients Many times toxicity occurs quickly and supportive care and administration of an antidote in a timely manner is crucial Pharmacists play an essential role in identifying toxicities, monitoring patients, and dosing medications in ALL poisoned patients

Hoffman RS, Howland M, Lewin NA, Nelson LS, Goldfrank LR. Principles of Managing the Acutely Poisoned or Overdosed Patient. In: Hoffman RS, Howland M, Lewin NA, Nelson LS, Goldfrank LR. eds. Goldfrank's Toxicologic Emergencies, 10e. New York, NY: McGraw-Hill; 2015.http://accesspharmacy.mhmedical.com.ezproxy.hsc.usf.edu/content.aspx?bookid=1163&Sectionid=65089354. Accessed February 15, 2015.. Hoffman R.S., Nelson L.S., Goldfrank L.R., Howland M, Lewin N.A., Flomenbaum N.E.(2011). Chapter 3. Initial Evaluation of the Patient: Vital Signs and Toxic Syndromes. In Nelson L.S., Lewin N.A., Howland M, Hoffman R.S., Goldfrank L.R., Flomenbaum N.E.(Eds), Goldfrank's Toxicologic Emergencies, 9e . Retrieved March 15, 2014 fromhttp://accesspharmacy.mhmedical.com.ezproxy.hsc.usf.edu/content.aspx?bookid=454&Sectionid=40199367. Chyka P.A. (2011). Chapter 14. Clinical Toxicology. In DiPiro J.T., Talbert R.L., Yee G.C., Matzke G.R., Wells B.G., Posey L (Eds), Pharmacotherapy: A Pathophysiologic Approach, 8e. Retrieved March 15, 2014 fromhttp://accesspharmacy.mhmedical.com.ezproxy.hsc.usf.edu/content.aspx?bookid=462&Sectionid=41100780.

Olson KR. Chapter 1. Emergency Evaluation and Treatment. In: Olson KR. eds.Poisoning & Drug Overdose, 6e. New York, NY: McGraw-Hill; 2012.http://accessmedicine.mhmedical.com.ezproxy.hsc.usf.edu/content.aspx?bookid=391&Sectionid=42069814. Accessed February 15, 2015. Hoffman R.S., Nelson L.S., Goldfrank L.R., Howland M, Lewin N.A., Flomenbaum N.E.(2011). Chapter 3. Initial Evaluation of the Patient: Vital Signs and Toxic Syndromes. InNelson L.S., Lewin N.A., Howland M, Hoffman R.S., Goldfrank L.R., Flomenbaum N.E.(Eds), Goldfrank's Toxicologic Emergencies, 9e . Retrieved March 15, 2014 fromhttp://accesspharmacy.mhmedical.com.ezproxy.hsc.usf.edu/content.aspx?bookid=454&Sectionid=40199367. Denshaw-Burke M. (2013). Methemoglobinemia. Medscape. Retrieved from http://emedicine.medscape.com/article/204178-overview Katselou M, Papoutsis I, Nikolaou P, et al. A “Krokodil” emerges from the murky waters of addiction. Abuse trends of an old drug. Life Sci. 2014; 102 (2); 81-7. doi: 10.1016/j.lfs.2014.03.008 Hahn I. Arthropods. In: Hoffman RS, Howland M, Lewin NA, Nelson LS, Goldfrank LR. eds. Goldfrank's Toxicologic Emergencies, 10e. New York, NY: McGraw-Hill; 2015.http://accesspharmacy.mhmedical.com.ezproxy.hsc.usf.edu/content.aspx?bookid=1163&Sectionid=65101715. Accessed February 18, 2015.

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