Basic Toxicology

Abdulaziz Saddique Pharm.D., CPHQ

11/12/2012

Epidemiology

2 million calls 52% of poison center calls < 6years Peak age 18 months - 3 years

11/12/2012

Epidemiology

Unintentional (1-2 years)

Exploratory Boys > girls

Purposeful Girls > boys

Intentional (adolescent)

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Children are different

Unable to discriminate safe from unsafe liquid Fail to recognize the suitability of the drink

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Epidemiology

Around Meal time Grand parents home Kerosene or gasoline in a soda bottle Older sibling can pharmaceutically treat younger sibling

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Very toxic!

Prenatal vitamin supplements Antidepressants Hydrocarbons

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Most often reported

Cleaning products Analgesics Cosmetics Cough & cold preparation Insecticides

10.4% 10.3% 9% 5.1% 4%

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ICU Admission

TCA Anticonvulsants Digitalis Opiates Hydrocarbon-based house-hold products

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Toxic Exposures/Death

Analgesics Sedative-hypnotics Alcohols Gases & fumes Cleaning substances

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Fatal Sip

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Fatal Sip

Camphor (100mg/kg) Methyl Salicylate (200 mg/kg)

1gm/5 ml 1.4gm/ml 1/2 tsp

11/12/2012

Fatal Sip

Benzocaine

2 ml

Methemoglobinemia Seizure

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Malignant Swallow

Chloroquine (20 mg/kg) Theophylline (8.4 mg/kg) Imipramine (15 mg/kg) Chlorpromazine (25 mg/kg)

500 mg 500 mg 150 mg 200 mg

11/12/2012

Malignant Swallow

Clonidine

0.3 mg tablet

Bradycardia CNS depression

11/12/2012

Highly Toxic

Acetonitrile Ammonium Fluoride Benzocaine Camphor Pennyroyal Oil

11/12/2012

Acetonitriles

Artificial Nail Tip remover Methemolobinemia Delayed presentation (4-12 hours) Must be hospitalized

11/12/2012

Ammonium Fluoride

Glass etching, de-rusting and wheel cleaning commercial products Armoral Quick Silver Wheel cleaner (17% ammonium fluoride) only 2 ml

11/12/2012

Ammonium Fluoride

Inactivates proteolytic & glycolytic enzymes Binds with Ca & Mg

Acidosis, Dysrhythmia & coagulopathy Seizures

Direct effect on CNS

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Benzocaine

Teething gels (Orajel), first aid cream hemorrhoidal preparations Methemoglobinemia < 6 months (methemoglobin reductase)

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Camphor

Vicks VapoRub Only 5 ml CNS effects

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Pennyroyal Oil

Health food products, herbal preparations Depletes glutathione Toxicity to liver & lung < a teaspoon A tablespoon (fatal)

11/12/2012

Look-Alike, Sound-A-Like

Albuterol Celebrex Oruvail Lamictal Lotrimin Plendil

Atenolol Cerebrex Elavil Lomotil Lotensin Pindolol

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Look-Alike, Sound-A-Like

Hydralazine Hydrocodone

Hydroxyzine Hydrocortisone

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Plant Toxidromes

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Digitalis Effects

Lily-of-the-valley Foxglove Oleander Yew

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Nicotinic Effects

Poison hemlock

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Atropinic Effects

Jimsonweed

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Non-Toxic Products

Ball point ink Bubble bath soaps Candles (beeswax or paraffin) Chalk Cigarettes (< 3 butts) Crayons

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Non-Toxic Products

Deodorants Lipstick Pencil (graphite) Toothpaste Water colors

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Evaluation

History of poisoning Toxicologic physical examination Laboratory studies Gastrointestinal decontamination

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History
What? When? How much?

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What ?
Medication Illicit

drug Hazardous chemical

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What form?
Pill Solid Liquid Gaseous

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What route ?
Ingestion Inhalation Topical Intravenous

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When ?
Elapsed

time

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How much ?
Estimate

amount Concentration

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Vital signs

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Bradycardia
Digoxin Narcotics Organophosphates Carbon

monoxide Beta-blocker
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Tachycardia
Alcohol/amphetamine Atropine/tricyclic Theophylline Salicylates,

Iron Cocaine/PCP
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Slow Respiration
Alcohol Narcotics Clonidine Sedatives

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Tachypnea
Amphetamines Salicylates Carbon

monoxide

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Hypotension
Methemoglobinemia Carbon

monoxide Cyanide Iron Narcotics

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Hypertension
OTC

cold remedies Amphetamine PCP TCA Cocaine

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Ventricular Tachycardia
Amphetamines Carbamzepine Chloral hydrate Cocaine Digitalis Theophylline

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Torsades de Pointes
Chloral hydrate Cisapride Organophosphates Terfenadine Phenothiazines

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Hypoglycemia (HOBBIES)

H-Hypoglycemia O-Oral hypoglycemic agents B-Beta-Blockers I-Insulin E-Ethanol S-Salicylates

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Hypothermia
Ethanol Narcotics Carbon

monoxide

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Hyperpyrexia
Atropine Salicylates Theophylline Cocaine TCA

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Mental Status

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Coma
Narcotic Anticholinergic Carbon

monoxide

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Delirium/Psychosis
Alcohol PCP/marijuana LSD

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Convulsion
Cocaine/Amphetamine Lead Salicylate Isoniazid Theophylline

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Pupil size

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Miosis (COPS)
Cholinergics,

Clonidine Opiates, Organophosphates Phenothiazine, Pilocarpine Sedatives (Barbiturates)

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Mydriasis (AAAS)

Antihistamine Antidepressant Anticholinergics (atropine) Sympathomimetics

Amphetamine, Cocaine, PCP

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Caution!
Polydrug overdoses with opposite pupillary actions Nontoxin diagnoses

Head trauma CNS hemorrhage

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Cyanosis
Unresponsive to oxygen

methemoglobinemia

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Cyanosis
Aniline Nitrites Benzocaine Dapsone

dyes

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Dry Skin
Anticholinergic

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Breath Odors

Arsenic Camphor Cyanide Methyl salicylate Paraldehyde

Garlic Mothballs Bitter almond Wintergreen Pears

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Toxidromes

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Cholinergic
DUMBBEL SLUDGE
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DUMBBELS
D

Diarrhea U Urination M Miosis, muscle fasiculation B Bradycardia B Bronchospasm

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DUMBBELS
E

Emesis L Lacrimation S Salivation

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SLUDGE
S

Salivation L Lacrimation U Urination D Diarrhea

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SLUDGE
G

GI complaint E Emesis

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Anticholinergic Syndrome

Dry mouth Flushed appearance Dilated pupils Fever Ileus Urinary retention Disorientation

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Anticholinergic
Hot as a hare Blind as a bat Dry as a bone Red as a beet Mad as a hatter

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Anticholinergic

Full as a flask

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Anticholinergic

Anticholinergic

Sympathomimetic

Wet Bowel sound +

Dry Absent bowel sound

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Narcotic
Pinpoint Coma Respiratory

pupils depression

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Salicylates
Fever Tachypnea & hyperpnea Lethargy Metabolic acidosis

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Theophylline
Protracted Vomiting Tremors Tachycardia Seizures Hypotension

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Isoniazid
Seizures Metabolic acidosis Hyperglycemia

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Phencyclidine (4 Cs)
Combative Catatonia Convulsion Coma Nystagmus

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TCA
Metabolic acidosis Prolonged QRS Seizures Dilated pupils Dysrhythmia

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Cyanide
Feeling of impending doom Sudden coma Metabolic acidosis Hypotension Bitter almond odor

11/12/2012

Carbon monoxide
Headache Lethargy Dizziness Influenza like syndrome Coma

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Ethanol
Hypoglycemia Lethargy Ataxia Seizure Characteristic breath odor

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Methanol
Severe Metabolic acidosis Sluggish pupils Hyperemic retina Blurred vision

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Ethylene Glycol
Lethargy or coma Metabolic acidosis Urinary sediment Crystalluria

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Clonidine

Hypothermia Bradycardia Miosis Respiratory depression

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Elevated anion gap

Methanol Paraldehyde & phenformin Iron & isoniazid Ethylene glycol & ethanol Salicylate

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ABCs
Anticipate Before

Complications

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ABC
Airway
C-spine

immobilization

Breathing Circulation
secure

IV access

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ABC
Disability
consciousness

Drugs Decontamination

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consciousness
A:

Alert V: Responsive to verbal stimuli P:Responsive to pain U: Unresponsive

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Drugs
Dextrose Oxygen

Naloxone

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Decontamination
Ocular-

copious saline lavage Skin- copious water GI-consider options

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Lab Evaluation
No tox panel that is uniformly helpful
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Urine Screen

Marijuana Amphetamines Barbiturates Cocaine Opiates PCP

5-10 days 48 hours 24 h-2 wks 2-4 days 2 days 8 days

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EKG
All suspected ingestion Tricyclics
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Pulse oximetry
Measure of oxygen saturation of normal hemoglobin
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Pulse oximetry
Does not differentiate COHB
from oxyhemoglobin

11/12/2012

False low Saturation

Blue

nail polish Methylene blue Poor distal perfusion

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Blood gas
Salicylates

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Chest X-ray
Hydrocarbons

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Esophagoscopy
Caustics

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Emergent Lab Analyses

Acetaminophen Salicylates Methanol Ethylene glycol Iron

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Emergent Lab Analyses

Theophylline Carbon monoxide Lithium

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Optimum time
Actaminophen Salicylates Iron Carboxyhemoglobin Methemoglobin

4 hours 2-4 hours 4 hours Immediate Immediate

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Optimum time
Ethanol Ethylene glycol Methanol Digoxin

1/2-1 hour 1/2-1 hour 1/2-1 hour 4-6 hour

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Serial Levels

Salicylates Carbamazepine Digoxin Phenobarbital Theophylline Valproic acid

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Radiopaque (CHIPS)
Chloral hydrate Heavy metals Iron Phenothiazine Slow release

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GI. Decontamination
Preventing absorption

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GI decontamination in a symptomatic patient?

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Decontamination
Syrup

of Ipecac Gastric lavage Activated Charcoal Cathartics WBI (bowel irrigation)

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Syrup of ipecac

11/12/2012

Syrup of Ipecac
Nonprescription CTZ

stimulant use only under poison control direction

11/12/2012

Syrup of Ipecac
No evidence of improved outcome Delays AC or antidote for 2 hours No role in hospital setting

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Adverse effect
Protracted Sedation Diarrhea Bradycardia

vomiting

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Contraindications
Altered Seizure Hemetemesis hydrocarbon corrosives

mental status

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Contraindications
Anticipated

use of oral antidote or WBI < 6 months old

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Gastric Lavage

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Gastric Lavage

one hour (golden hour)

threatening ingestion

Life

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NG tube is not adequate

11/12/2012

Gastric Lavage
Large

bore orogastric tube (36 - 40 French) 0.9% saline 15 ml/kg max 200-400 ml/cycle

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Gastric Lavage
<

30% by 20-30 min < 13% by 60 minutes

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Gastric Lavage
Not a routine With in one hour Life-threatening ingestion Absence of pill fragments does not rule out toxic ingestion

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Gastric Lavage
TCA Calcium-blocker Colchicine

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Complications
Pulmonary

aspiration

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Contraindications
Caustic Hydrocarbon Sharp

co-ingestion

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Activated Charcoal
Universal antidote

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Single dose AC
adsorbing the ingested substance
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Activated Charcoal
Oxidizing process Increases the adsorptive capacity Inert substance Reduce the bioavailability of drug

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Activated Charcoal
Surface area 2/g 950-2000m
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Poorly bound by AC

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CHEMICaL CamP

C H E M I C L

Cyanide Hydrocarbon Ethanol Metals Iron Caustics Lithium

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CHEMICaL CamP

C Camphor P Phosphorus

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Recommended Dose
Up

to 1 year year
gm

1g/kg

1-12

25-50

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Complications
Pulmonary Emesis Constipation

aspiration

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Contraindications
Hydrocarbon Corrosive Ileus

11/12/2012

Home AC?

1,208,860 exposure in < 6 year 16 fatalities 4 might have benefited from early administration of AC American Association of Poison Control Centers Toxic Exposure Surveillance System (1998)

11/12/2012

Benefits of Home AC
Early administration Reduced morbidity & mortality

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Risks of Home AC
Inappropriate administration Inadequate dosing Pulmonary aspiration

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Multiple-Dose AC
Gastrointestinal Dialysis

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Multiple-Dose AC

Continue to adsorb remaining toxin Interfere with enterohepatic circulation Lower the free drug concentration

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Multiple-Dose AC

Phenobarbital Carbamazepine Phenytoin Digoxin Salicylates Theophylline TCA

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Cathartics
Decrease transit time

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Cathartics
Sorbitol

70%(0.5g/kg) 10 - 20 ml (children) 50-100ml(adolescent)

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Complications
Nausea Abdominal Vomiting Transient

cramps

hypotension

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Contraindications
Unprotected Ileus Absent

airway

bowel sounds Intestinal obstruction

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WBI
Decontaminate entire gastrointestinal tract
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WBI
Commonly used for agents not bound to activated charcoal
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WBI

polethylene glycol

No fluid abnormality No electrolyte imbalance End point clear rectal effluent Sustained release preparation

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WBI
9

months to 6 years
ml/hr

500

6-12

years (1000 ml/hr) over 12 years

1500-2000

ml/hr

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WBI
Calcium-channel-blockers Iron Arsenic Lead/zinc Packets

of illicit drugs

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Complications
Nausea

& vomiting Bloating / cramps Pulmonary aspiration

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Urinary Alkalinization
Salicylates Phenobarbital Chlorpropamide

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Urinary Acidification
Never indicated Systemic acidosis Renal impairment in myoglobinuria

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Extracorporeal Clearance

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Hemodialysis
Severe poisoning Renal failure

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Hemodialysis
8-10 fold increased clearance Corrects acid-base imbalance Corrects electrolyte imbalance

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Hemodialysis
Small molecular weight Non-ionized, uncharged molecule Low plasma protein binding Small volume of distribution (<1.0L/kg)

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Hemodialysis
Lithium 4 mEq/L Ethylene glycol 50 mg/dl Methanol 50 mg/dl Salicylates 100 mg/dl

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Hemoperfusion

A charcoal or resin cartridge More effective in selected poisonings Not limited by plasma protein binding Not limited by molecular size

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Hemoperfusion

Not effective for acid-base & electrolyte imbalance correction Ineffective in patients with renal failure

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Hemoperfusion
Phenobarbital Theophylline Paraquat Glutethimide Meprobamate

100 mg/L 60-100mg/L 0.1 mg/dl 4 mg/dl 10 mg/dl

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Antidotes

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Antidotes
Use only if specific criteria met
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Immediate use
Oxygen
carbon

monoxide

Naloxone
Opioids

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Immediate use
Methylene
severe >

blue 1%

cyanosis

40%

11/12/2012

Immediate use
Sodium
Cyanide

nitrite

Deferoxamine
Iron

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Antidotes

Acetaminophen - N-Acetylcysteine
140 mg/kg PO 70 mg/kg q4h for 17 doses

Anticholinergics - Physostigmine

0.5 mg IV

11/12/2012

Antidotes

Organophosphates
Atropine 0.05-0.1 mg IM or IV Pralidoxime 25-50 mg/kg IV

11/12/2012

Antidotes

Benzodiazepine - Flumazenil

0.01 mg/kg IV

Beta Blockers

- Glucagon

50 ug/kg IV

11/12/2012

Antidotes

Isoniazid

Pyridoxine 5-10% NaHCO3 Vitamin K

1 gm/gm of INH ingested IV

TCA

1-2 mEq/kg IM or IV 1-5 mg IV or IM

Warfarin

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New Antidotes

11/12/2012

New Antidotes

Glucagon

Beta-blocker & Ca-channel blocker

Insulin & glucose ?

Ca-channel blocker Octreotide Sulfonylureas induced hypoglycemia

11/12/2012

New Antidotes

Tricyclic antidepressant antibodies

TCA
Methanol & ethylene glycol Opioid poisoning Benzodiazepine

Fomepizole (Antizol)

Nalmefene

Flumazenil (Romazicon)

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Take home message

Basic supportive care has saved more lives than all the antidotes put together Small quantities can have significant consequences Most pediatric ingestion are trivial

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If you watch these kids, you may not have to do anything

11/12/2012

Resources
Drug Information (AHFS) Poisindex computer database

Regional poison center

212-POISONS

11/12/2012