jami johnson's scheffe 2019 slides€¦ · tasteless gas why co binds tightly to hemoglobin...

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Toxicology Take‐AwaysWalter P. Scheffe 2019 CPE Series

Jami Johnson, PharmD, DABATAssistant Director, Oklahoma Center for Poison & Drug Information

Assistant Adjunct Professor, OU College of Pharmacy

Financial Disclosure and ResolutionUnder guidelines established by the Accreditation Council for Pharmacy Education (ACPE), disclosure must be made regarding financial relationships with commercial interests within the last 12 months.

Jami Johnson

Commercial Interest

Nature of Relevant Financial Relationship

What was received? For what role?

Boston Scientific (BTG International, Inc.) Speaker Fee Speaker’s Bureau

The conflict was resolved by Dr. Johnson agreeing to refrain from making recommendations on topics in which the conflict exists and agreeing that the presentation will not include discussion of any products or services from the listed commercial interest. Presentation slides were reviewed for content validation and bias by the Continuing Education Administrator.

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At the completion of this activity, pharmacists will be able to:

1. Identify toxins known to cause serious adverse effects with small, inadvertent exposures

2. Recognize common substances not likely to cause serious adverse effects

3. Outline an appropriate management strategy for a patient exposed to a 'red flag' substance

4. Describe the mechanism of action of kratom

5. Identify the potential adverse effects from loperamide overdose

Learning Objectives

Pre‐Assessment Question #1

Which of the following substances may cause severe toxic effects following ingestion of just one tablet in a child?

A. Famotidine

B. Glipizide

C. Ibuprofen

D. Lisinopril

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Pre‐Assessment Question #2

Kratom has effects on which of the following receptors?

A. µ opioid receptors

B. D1 receptors

C. Κ opioid receptors

D. All of the above

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Non‐Toxic StuffNo worries

Very Toxic StuffWho

What

Why

What (to do‐immediate actions)

Opioids (I know)Kratom

Loperamide

Omeprazole + methadone

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OCPDI’s ‘Non‐Toxic’ List

OTC Medications• < 200 mg/kg acetaminophen/ibuprofen• melatonin• antacids• multivitamins• bulk‐forming laxatives• simethicone• calamine lotion• teething tablets• guaifenesin• homeopathy• < 10 mg/kg elemental iron

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OCPDI’s ‘Non‐Toxic’ List

• Prescription Medications

• birth control tablets

• cephalosporins

• corticosteroids

• levothyroxine

• montelukast

• penicillin/amoxicillin

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OCPDI’s ‘Non‐Toxic’ ListHousehold Products

• diaper rash ointment

• deodorant

• petroleum jelly

• art supplies (glues, pencils, pens, chalk)

• glow sticks

• Play‐Doh® (not home‐made)

• shampoo & conditioner

• candles

• make up

• lotions

• nail polish

• thermometers

• desiccants

• motor oil

• caulk/spackle 9

OCPDI’s ‘Red Flag’ List

calcium channel blockers (CCB)calcium channel blockers (CCB)

beta blockers (BB)

beta blockers (BB)

centrally acting alpha‐2 agonistscentrally acting alpha‐2 agonists

stimulantsstimulants antiarrhythmicsantiarrhythmics antimalarialsantimalarials

bupropionbupropion colchicinecolchicine opioidsopioidstricyclic

antidepressantstricyclic

antidepressantssulfonylureassulfonylureas toxic alcoholstoxic alcohols

black widow bites

black widow bites

organophosphates & carbamates


cyanidecarbon monoxide

(CO)hydrogen sulfide

(H2S)

cyanidecarbon monoxide

(CO)hydrogen sulfide

(H2S)

Micotil® (tilmicosin)Micotil®

(tilmicosin)hydrocarbonshydrocarbons snake bitessnake bites

button batteriesbutton batterieshydrofluoric

acidhydrofluoric

acidoil of

wintergreenoil of

wintergreenchlorfenapyrchlorfenapyr local anestheticslocal anesthetics

plants

mushrooms

plants

mushrooms

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Hydrocarbons

Who?Children (assume for all)

Self‐Harm (assume for all)

Workers

Intentional abusers

What?Carbon + Hydrogen +/‐ Halogen

• Fuels, lighter fluid, paint thinners, solvents, Freon

• Essential oils

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Hydrocarbons

Pulmonary Aspiration pneumonitis, disruption of surfactant

CNS General depressant (GABA agonists)

Cardiac ‘Sudden sniffing death’

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Immediate Actions

• Dermal

• Decontaminate with mild soap and water

• Aspiration• Call 911

• Inhalation Abuse• Avoid stress, call 911

• All exposures• Call OCPDI

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calcium channel blockers


beta blockersbeta blockerscentrally acting alpha‐2 agonistscentrally acting alpha‐2 agonists





black widow bites

black widow bites



cyanide/CO/H2Scyanide/CO/H2SMicotil®

(tilmicosin)Micotil®



acidhydrofluoric

acidoil of

wintergreenoil of


Plants

Mushrooms

Plants

Mushrooms

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Hydrofluoric Acid

Who?Children

Workers (auto detailing, refineries)

Craftsmen

What?Hydrogen + Fluorine

Industry‐ High octane fuel, electroplating, cleaning, dissolves

silica

Household use‐ Glass etching, rust removers, wheel cleaners

Why?Fluorine‐most electronegative element

• Binds calcium, magnesium, manganese

Acid‐ coagulative necrosis, ocular burns, white discoloration

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Hydrofluoric Acid‐Immediate Actions

Dermal

1. Decontamination2. Apply calcium

10g carbonate tablets in20mL lubricating gel

3. Apply magnesiumIf no access to calcium

Exposure to highly concentrated (>~5%) product

Call 911

All exposures

Call OCPDI

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black widow bites

black widow bites







acidhydrofluoric

acidoil of

wintergreenoil of


Plants

Mushrooms

Plants

Mushrooms

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Micotil® (tilmicosin)

Who?Veterinarians

Ranchers/farmers

What?Veterinary antibiotic approved for metaphylaxis for Bovine Respiratory Disease

• Mannheimia haemolytica, Pasteurella multocida, Histophilus somni

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• Why?

• Macrolide class of antibiotic, parenteral administration only

• Calcium channel antagonist in human cardiac muscle

• Hypotension, dysrhythmias expected following intravenous (IV) injection

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• Immediate actions

• Dermal

• Decontaminate with soap and water

• Absorption poor

• Any parenteral exposure

• Call 911

• All exposures

• Call OCPDI

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black widow bites

black widow bites

organophosphate & carbamates

organophosphate & carbamates





acidhydrofluoric

acidoil of

wintergreenoil of


Plants

Mushrooms

Plants

Mushrooms

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Organophosphates (OP) & carbamates

Who?

Agricultural workersVictims of chemical terrorism

What?

Nerve agents• soman, sarin, tabun, VX, Novichok agents

Pesticides• OPs‐parathion, diazinon, malathion (Spectracide®) dichlorvos (Hot Shot®)

• Carbamates‐aldicarb (Temik®), carbaryl (Sevin®)

Why?

Excess build‐up of acetylcholine by inhibition of acetylcholinesterase• Enzyme aging• + OP• ‐ carbamates

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Autonomic Nervous System

(Parasympathetic)

Acetylcholine Nicotinic cholinergic receptors

Muscarinic cholinergic receptors

NorepinephrineAlpha receptors

Beta receptors

End‐Organ

Parasympathetic Ganglion

CNSParasympathetic

stimulation

Acetylcholine nicotinic receptors

Acetylcholine muscarinic receptors

Acetylcholine nicotinic receptors

Norepinephrine alpha/beta receptors

acetylcholinesterase

Breaks down acetylcholine to

acetic acid & choline

OPs & carbamates

acetylcholinesterase

Breaks down acetylcholine to

acetic acid & choline

Excess Acetylcholine

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Cholinergic Toxidrome

• D• Diarrhea

• U• Urination

• M• Miosis (small pupils)

• B• BRADYCARDIA• BRONCHORRHEA/BRONCHOSPASM

• E• Emesis

• L• Lacrimation

• S• Salivation

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Cholinergic Toxidrome

• M• Mydriasis (dilated pupils)

• T• Tachycardia

• W• Weakness

• tH• Hypertension

• F• Fasciculations

organophosphates & carbamates• Immediate Actions

• Dermal

• Decontaminate with soap and water

• May have significant absorption

• Any respiratory symptoms or seizures

• Call 911

• All exposures

• Call OCPDI

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black widow bites

black widow bites







acidhydrofluoric

acidoil of

wintergreenoil of


Plants

Mushrooms

Plants

Mushrooms

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Cyanide• Who?

• Fire victims, industrial accidents, laboratory workers

• What?• Inorganic salts‐ plastic manufacturing, fumigation, mining• Closed space fires‐ victims and rescuers• Plants‐Prunus species• Miscellaneous‐ sodium nitroprusside, homicide, laboratory exposures

• Why?• Inhibition of multiple enzymes‐primarily cytochrome oxidase

• Enzyme responsible for oxidative phosphorylation• The last step of the electron transport chain• Cells cannot utilize oxygen, hydrogen ions begin to accumulate

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Carbon Monoxide (CO)

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Who

Occupational

Environmental

Fire

What

Formed during incomplete combustion of carbon‐containing compounds

• Odorless, colorless, tasteless gas

Why

CO binds tightly to hemoglobin decreasing offloading of oxygen

CO binds to mitochondrial cytochrome oxidase

Hydrogen Sulfide (H2S)

• Workplace exposures

• Sulfur decay (sewers/manholes/lagoons), oil & gas, natural gas drilling

• Environmental disasters

• Volcanoes, caves, sulfur springs, natural gas deposits

Who?

• Colorless, dense gas

• ‘rotten egg’ smellWhat?

• Inhibition of cytochrome oxidase > interrupt oxidative phosphorylationWhy?

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Cyanide/CO/H2S

• Immediate Actions

• Environmental

• Remove patient from poison

• Any known exposure (non‐prunus related)• Call 911


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black widow bites

black widow bites







acidhydrofluoric

acidoil of

wintergreenoil of


Plants

Mushrooms

Plants

Mushrooms

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Sulfonylureas

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Who?Children!!

Therapeutic errors

What?glipizide (Glucotrol®)

glyburide (Diabeta®, Micronase®)

glimepiride (Amaryl®)

Why?Hypoglycemia

• Delayed/prolonged

glucose

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glucose

ATP ↑↑ K+

depol

↑↑Ca2+

insulin exocytosis

sulfonylureas

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Immediate Actions

• Hypoglycemia

• Oral glucose supplementation if safe

• Glucagon not recommended

• All exposure in naïve patients• Refer to emergency department


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black widow bites

black widow bites







acidhydrofluoric

acidoil of

wintergreenoil of


Plants

Mushrooms

Plants

Mushrooms

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Tricyclic Antidepressants

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Who?Suicidal patients (recent initiators)

Accidental ingestions (pain, children, etc.)

What?

Tertiary‐ imipramine, amitriptyline, clomipramine, doxepin, trimipramine

Secondary‐ amoxapine, desipramine, nortriptyline, protriptyline, maprotiline

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Tricyclic Antidepressants‐ why?

Serotonin & norepinephrine reuptake inhibitors

Anticholinergic activity

Alpha blocking activity

Sodium channel blocking activity

Seizure activity (multifactorial)

Immediate Actions

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All intentional exposures

Call 911 or take to nearest emergency department

All exposures

Call OCPDI

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black widow bites

black widow bites







acidhydrofluoric

acidoil of

wintergreenoil of


Plants

Mushrooms

Plants

Mushrooms

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colchicine

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• Who?• Therapeutic errors (pain)• Accidental exposures• Suicidal ingestions

• What?• Colchicum autumnale‐Autumn crocus, naked lady• Gloriosa superba‐Glory lily• Colchicine‐ utilized for gout

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colchicine

• Why?

• Inhibitor of microtubule formation/function

• Interferes with cellular mitosis, intracellular transport mechanisms, maintenance of cell structures and shape

• Cell dysfunction & death

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Immediate Actions


• Any intentional exposure• Call 911• Early intervention


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black widow bites

black widow bites







acidhydrofluoric

acidoil of

wintergreenoil of


Plants

Mushrooms

Plants

Mushrooms

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The Therapeutic Error

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• TID IR > Daily XR• Bupropion ER 450 mg tablets

• Initial thoughts?

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Bupropion

• Who?

• All‐comers

• What?

• Mechanism of action (MOA) not well understood

• Noradrenergic or dopamine activity

• Minimal effects on monoamine oxidase or serotonin uptake

• Why?

• Metabolite hydroxybupropion

• Cathinone‐sympathomimetic and alpha agonist properties

• Seizures, conduction disturbances

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• Retrospective Review

• 4 poison centers

• 2000‐2006

• Children < 6 years

• 407 bupropion exposures

• Clinical findings

• Seizure (0.7%)

• Sinus tachycardia (12.3%)

• Author Conclusions

• Mean dose (ST)= 24 mg/kg (11‐64)

• Mean dose (seizure)= 39 mg/kg (34‐44)

• Max dose (no effects)= 10 mg/kg (SD +/‐ 7.9)

• Versus 18.6 mg/kg (SD +/‐ 13.4), p<0.05

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• Retrospective Review• TESS database (2000‐2003)

• 476 bupropion therapeutic errors• Age: 13‐92 years (SD 40 +/‐ 16 years)

• 354 (74.4%) female

• 412 (86.6%) sustained release formulation

• Author Findings• Mean dose= 300 mg (75‐1,500 mg)

• All seizures= < 450 mg

• Moderate/major effects in >10%

• Clinical Findings (mild)• N/V (6.7%), drowsiness (6.1%)

• Clinical Findings (moderate)• Tachycardia (5.5%)

• Tremor (7.1%)

• Dizziness (7.4%)

• Clinical Findings (major)• Agitation (8.2%)

• Seizures (0.8%)

• Hallucinations (0.4%) 49

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Immediate Actions

Therapeutic Errors

• Refer all long acting formulations

Any intentional exposures

• Call 911 or take to nearest ED if safe

All exposures

• Call OCPDI









black widow bites

black widow bites







acidhydrofluoric

acidoil of

wintergreenoil of


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Mushrooms

Plants

Mushrooms

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Opioids

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• Who?• Anyone with access

• What?• Prescription medications• Illicit substances‐heroin, fentanyl derivatives• Miscellaneous sources‐ loperamide, kratom• Buprenorphine & diphenoxylate

• Why?• CNS/respiratory depression• Cardiac/CNS toxicity

Immediate Actions

• Administer antidote

• Naloxone

• Any CNS or respiratory depression• Call 911


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black widow bites

black widow bites







acidhydrofluoric

acidoil of

wintergreenoil of


Plants

Mushrooms

Plants

Mushrooms

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Antiarrhythmics & antimalarials

• Who?

• Therapeutic errors

• Inadvertent ingestions

• What?

• Antiarrhythmic‐ procainamide, disopyramide, flecainide, propafenone, dofetilide, amiodarone, dronedarone, sotalol

• Antimalarials‐ quinidine, chloroquine, hydroxychloroquine

• Why?

• Narrow therapeutic window

• Toxicity‐Extension of therapeutic effects

• Chloroquine cardiac toxicity >>> hydroxychloroquine

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• Any intentional exposure• Call 911 or take to nearest ED if safe










black widow bites

black widow bites







acidhydrofluoric

acidoil of

wintergreenoil of


Plants

Mushrooms

Plants

Mushrooms

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Stimulants

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Who?

• Inadvertent exposures, abuse/misuse

What?

• Pharmaceuticals‐ amphetamine salts, phentermine, ephedrine, pseudoephedrine, theophylline, vasopressors (norepinephrine, epinephrine, phenylephrine), ketamine, caffeine

• Drugs of abuse‐methamphetamine, MDMA, synthetic cannabinoids, synthetic cathinones, cocaine, PCP & derivatives, nicotine

Why?

• Alterations in neurotransmitters > end‐organ dysfunction

• CNS, cardiac, renal, autonomic dysfunction


• Therapeutic errors• Dependent upon agent and age/clinical picture

• Any parenteral exposure• Call 911 or take to nearest ED


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black widow bites

black widow bites







acidhydrofluoric

acidoil of

wintergreenoil of


Plants

Mushrooms

Plants

Mushrooms

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Calcium Channel Blockers (CCB) and Beta Blockers (BB)

• Who?

• Inadvertent ingestions

• Suicidal patients

• What?

• BB‐ bisoprolol, atenolol, nebivolol, metoprolol, acebutolol, nadolol, carvedilol, labetalol, penbutolol, propranolol

• CCB‐ diltiazem, verapamil, amlodipine, nicardipine, nimodipine, nifedipine, felodipine, nisoldipine, isradipine

• Why?

• Narrow therapeutic index

• Toxicity‐extension of therapeutic effects

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• Therapeutic errors• Dependent upon medication and situation

• Any intentional exposure• Call 911


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Toy Hall of Shame

Aquadots® and Bindeez®

• Beads coated with 1,4‐butanediol

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Sciencelab.com

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Daphne (1.2 mg)‐

15 minutes‐ ‘Don’t care one bit about the 9‐5 stuff that I was worrying about 15 minutes ago’

25 minutes‐ ‘Starting to ramp up a bit, feeling nauseous, getting dizzier’

35 minutes‐ ‘*very* dizzy’‘I kind of like the body‐high: legs feel wobbly and kind of vibrating”

Kamack (1.6 mL)‐

‘Take at cocktail hour for general relaxation & stimulation of growth hormone. Also take ¾ dose before exercise to increase endurance.’

Jason (5 mL)‐

0 min: 3mL‐ no effect

30 min: + 1 mL‐ ‘Remember, you can always take more drugs, but once you take too much, you’re f***ed’

60 min: + 1mL‐ ‘Feel like going for a walk’

~2 hours: ‘having a slightlyharder time keeping my balance walking around, but that's alright as I don't really have to go anywhere’

~6 hours: ‘My stomach is upset’

~8 hours: ‘I crash’

https://www.erowid.org/experiences/subs/exp_14Butanediol.shtml

https://www.erowid.org/experiences/exp.php?ID=29274https://www.google.com/search?q=sceptical+meme&rlz=1C1EODB enUS595US595&espv=2&biw=1280&bih=899&source=lnms&tbm=isch&sa=X&ved=0CAYQ AUoAWoVChMI2I 7wZ66xwIVhB8eCh0oQQrs#imgrc= YyF6QfuAUx xM%3A

Chromodynamix‐

“I am a qualified Pharmacologist, so I ‘should’ have known better…On a Sunday afternoon, I decided to have a ‘nap’. Instead of measuring the amount into some grapefruit juice, I ‘estimated’ the amount…BAD MOVE! …Next thing I remember were paramedics checking me out and coming round in emergency resuscitation. I had already had a brain scan as they suspected a stroke and I had been intubated. They started discussing doing a lumbar puncture and possible ‘brain surgery,’ and all this time I am trying to explain I was a qualified Pharmacologist and I was not in any danger.

Addendum‐ I mentioned mixing the 1,4‐Butanedoil with grapefruit juice. There are many drug ‘interactions’ with grapefruit juice, which inhibits an enzyme Cytochrome P 450 in the intestinal wall. This can cause much higher concentrations of a drug to get to the blood stream with dangerous results. I am convinced this led to the ‘OD reaction.’”

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Pharmacology‐Pharmacology‐ Schep, et al. Clin Tox. 2012; 50: 458‐470.




beta blockersbeta blockerscentrally acting

alpha‐2 agonists

centrally acting alpha‐2 agonists





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black widow bites







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acidoil of

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Centrally acting alpha2 agonists

• Who?

• Children, therapeutic errors, intentional ingestions, malicious intent

• What?

• Clonidine, tizanidine, guanfacine, dexmedetomidine, tetrahydrozoline, oxymetazoline

• Why?

• Act on alpha‐2 receptors in the CNS to decrease sympathetic tone

• CNS/respiratory depression, hypotension, bradycardia

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Immediate Action


• Therapeutic errors• Dependent upon medication and situation

• Any intentional exposure• Call 911


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black widow bites

black widow bites







acidhydrofluoric

acidoil of

wintergreenoil of


Plants

Mushrooms

Plants

Mushrooms

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Oil of Wintergreen

• Methyl salicylate• 100% is most common formulation• 5mL (1 mouthful) = 5g methyl salicylate• 1.5g aspirin equivalents per 1g methyl salicylate

• 7.5g aspirin (equivalent) per 5mL• For a 30lb child (13.6kg)

• 551.5 mg/kg• Threshold for referral is 150 mg/kg

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black widow bites

black widow bites







acidhydrofluoric

acidoil of

wintergreenoil of


Plants

Mushrooms

Plants

Mushrooms

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The U.S. Opioid Epidemic

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Prescription opioids

Alternative Prescription Opioids

Traditional illicit opioids

Non‐Traditional illicit opioids

Opioid alternatives

The ‘Roots’ of Kratom

• Family: Rubiaciae

• Genus: Mitragyna

• Species: speciosa

Indigenous to:• Southeast Asia• The Philippines• New Guinea

White CM. Am J Health Syst Pharm. 2018; 75(5): 261‐267.Kaye et al. Best Pract Res Clin Anaesthesiol. 2018; 32(2): 125‐136.

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• Thai kratom extract composition:

• Mitragynine (66%)

• Paynantheine (9%)

• Hydroxymitragynine (2%)

• Speciogynine (7%)

• Speciociliatine (1%)

• 40 structurally related alkaloids, also flavonoids, terpenoid saponins, polyphenols and glycosides

White CM. Am J Health Syst Pharm. 2018; 75(5): 261‐267.Kaye et al. Best Pract Res Clin Anaesthesiol. 2018; 32(2): 125‐136.Feng et al. J Food Drug Anal. 2017; 25(3): 461‐471.


• Ketum

• Kakuam

• Ithang

• Thom

• Mambog

Kaye et al. Best Pract Res Clin Anaesthesiol. 2018; 32(2): 125‐136.

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Kratom Use

• Fresh or dried leaves• Chewed• Made into a tea

• Traditional Uses• Improve productivity• Fight fatigue• Religious ceremonies

• Modern Uses• Opioid dependence• Opioid substitute• “Enhancer”• 4x100 (kratom, cough syrup, Coca‐Cola, ice)


1943 Prohibited in Thailand

1952 Prohibited in Malaysia

2011 Controlled in Denmark, Poland, Sweden, Latvia and Romania

2014 FDA banned importation & manufacturing (Schedule I status‐ did not stick)

2015 Australia & New Zealand

Considered a narcotic

2016 UK prohibited sale, import and export

2017 Schedule I substance in Republic of Ireland

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Mitragynine

Active at δ, μ, and κ opioid receptors

No structural similarity to morphine

Broad binding capacity

dopaminergic, serotonergic, gabaminergicand adrenergic pathways, COX inhibition

Ponglux, et al. Planta Medica. 1994; 60(6): 580–581. Horie, et al. Planta Medica. 2005; 71(3): 231–236. Takayama, et al. Chemical and Pharm Bulletin. 2004; 52(8): 916– 928.

7‐hydroxymitragynine

Active at μ, and κ opioid receptors and alpha‐2 receptors

No structural similarity to morphine

Broad binding capacity

dopaminergic, serotonergic, gabaminergic and adrenergic pathways, COX inhibition

Consideration for standardizationPonglux, et al. Planta Medica. 1994; 60(6): 580–581. Horie, et al. Planta Medica. 2005; 71(3): 231–236. Takayama, et al. Chemical and Pharm Bulletin. 2004; 52(8): 916– 928.

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Speciociliatine

Active at μ and κ opioid receptors

Not inhibited by naloxone

Takayama, et al. Chemical and Pharm Bulletin. 2004; 52(8): 916– 928.

Mild stimulant effects

• Similar to caffeine/nicotine

Opioid‐like effects

• Analgesia

• Sedation

• Respiratory depression

5‐15 m

g (m

oderate/high dose)

1‐5 m

g (low/m

oderate

dosin

g)


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• Bitter taste

• Feeling hot/sweaty

• Itchiness

• Hangover (similar to alcohol)

• Mild depressed mood

• Desire to repeat use

• Difficulty controlling use

• Building tolerance quickly

• Empathy• Euphoria• ‘Nodding’• ↓ opioid withdrawal symptoms

• Aphrodisiac• Increased sociability • Increased talkativeness

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Drug Interactions

Stimulants

Sedatives

Hypnotics

Disease Interactions

Depression

Addiction

Liver disease

White CM. Am J Health Syst Pharm. 2018; 75(5): 261‐267.

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Loperamide‐ 'poor man's methadone'

Binds to mu opioid receptors on the intestinal wall > decrease peristalsis

Maximum daily dose 16mg Available OTC

Lee et al. Clin Toxicol. 2018. Epub ahead of print: doi 10.1080/15563650.2018. 1510128

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Loperamide

• Pharmacokinetics

• Low oral bioavailability (<1%)

• High first pass metabolism

• Metabolized via CYP3A4

• Poor penetration into the CNS • P‐glycoprotein efflux

Lee et al. Clin Toxicol. 2018. Epub ahead of print: doi 10.1080/15563650.2018. 1510128Wu et al. Ann Emerg Med. 2017; 70(2): 245‐252.

Crafty Chemists

Add CYP 3A4 inhibitors to increase serum concentration

Grapefruit juice

Cimetidine

Inhibit P‐glycoprotein to improve blood brain barrier penetration

Omeprazole

Ingestion of supratherapeutic doses

25‐800mg daily

Lee et al. Clin Toxicol. 2018. Epub ahead of print: doi 10.1080/15563650.2018. 1510128Wu et al. Ann Emerg Med. 2017; 70(2): 245‐252.

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Loperamide abuse & misuse

• Initially used as opioid alternative for euphoria

• Followed by reports of arrhythmias

• More commonly used for withdrawal symptoms

Loperamide abuse & misuse

• Loperamide= $0.09/mg• 200mg= $18.00/day

• Oxycodone= $1.00/mg

• Heroin= $0.02‐$0.40/mg

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Clinical Effects

Opioid Toxidrome

CNS & respiratory depression, miosis, constipation

Sodium Channel Blockade

Prolonged QRS interval, dysrhythmias

Potassium Channel Blockade

Prolonged QT interval, dysrhythmiasMacdonald et al. BMJ Case Rep. 2015.

Eggleston et al. Annals of Emergency Medicine. 2017; 69(1): 83‐86. Wu et al. Ann Emerg Med. 2017; 70(2): 245‐252.

Methadone Kinetics

Orally administered racemic mixture

Lipophilic, basic drug

Predominantly absorbed in small intestine

Oral bioavailability: 41‐99%

N‐demethylation via CYP450 to inactive metabolites

3A4, 2B6, 2C19, 2C9, 2D6

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“Anecdotal “Evidence”

“Well I took one omeprazole (whatever the regular dose is, 20 mg i think) about an hour before taking methadone. I only took 10 mg, and it's still kicking in, but already it feels more like I took 15 mg. Not a huge difference, and it's still within the realm of possible placebo effect, but I actually believe there is some definite potentiation going on here.”

‐ Indy

“ … prolongs the duration of action of methadone very well.”

‐t1rex

Omeprazole Thefts Spark Change

“More than $3,500 worth of Prilosec OTC was stolen from a Suffolk Walmart.” –WVEC

2010

“Wanted: Battery and retail theft of Prilosec OTC Jewl‐Osco on Roselle Rd, Hoffman Estates” – The Cardinal

2011

“Over‐the‐counter theft receives police attention in Boone, NC” – Charlotte Criminal Lawyer Blog

2013

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Post‐Assessment Question #1

Which of the following substances may cause severe toxic effects following ingestion of just one tablet in a child?

A. Famotidine

B. Glipizide

C. Ibuprofen

D. Lisinopril

103

Post‐Assessment Question #2

Kratom has effects on which of the following receptors?

A. µ opioid receptors

B. D1 receptors

C. Κ opioid receptors

D. All of the above

104

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Toxicology Take‐AwaysWalter P. Scheffe 2019 CPE Series

Jami Johnson, PharmD, DABATAssistant Director, Oklahoma Center for Poison & Drug Information

Assistant Adjunct Professor, OU College of Pharmacy

jami johnson's scheffe 2019 slides€¦ · tasteless gas why co binds tightly to hemoglobin...

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