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…and that is what an antiseptic is. Clearly

different than a disinfectant.

He never shuts up. I’ll give him

something to disinfect.

The Toxic House

Kurt Kleinschmidt, MD Professor of Emergency Medicine Section Chief and Program Director; Medical Toxicology UT Southwestern Medical Center

•  Antiseptic •  Applied to living tissue •  Kills or inhibits microorganism •  Iodophores, Chlorhexidine, Alcohols

•  Disinfectant •  Applied to inanimate objects to kill microorganisms •  Hypochlorites, Phenolic agents, Formaldehyde

•  Sterilant •  Applied to inanimate object to kill all living organisms

(including spores) •  Ethylene oxide •  Glutaraldehyde

Household ���Cleaners

Phased out b/c of Toxicity: Iodine; Phenol; Mercuric chloride

Antiseptics – Disinfectants - Sterilants

•  Acids •  Boric Acid

•  Alchohols •  Aldehydes

•  Formaldehyde •  Glutaraldehyde

•  Chlorhexidine •  Chlorinated Items •  Ethylene Oxide •  Iodinated Items

•  Iodine •  Iodophores

•  Oxidants •  Hydrogen peroxide •  Potassium permanganate

•  Phenols •  Nonsubstituted •  Substituted

(Hexachlorophene) •  Quaternary Ammonium

Compounds •  Benzalkonium chloride

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Questions...

How toxic is iodine vs. iodide vs. Iodophore?

Iodine / Iodophores / Iodides

•  Iodine (I2; Free, Elemental, or Molecular) –  Active item in iodine based antiseptics –  Poorly soluble

•  Adding Iodide (I-) è é solubility •  Ethanol è é concentration

Tincture (2 g free iodine per 100 mL) •  Iodophores

–  Iodine è Attached to a carrier / solubilizer –  Povidone-Iodine (Betadine) –  Only 1% of iodine in a 10% solution of Betadine is freely

soluble (0.001% is free iodine) –  Free iodine…~ 80-120 mcg/100mL

Iodine / Iodophores / Iodides

Iodides (Reduced iodine (I-)) • Salts…Potassium or Sodium iodide • Potassium iodide è Treat hyperthyroidism & radiation exposure

• Sodium iodide è Dietary supplement (table salt) • Not an antiseptic itself…

• Combined with iodine (the antiseptic) • Tincture: EtOH + 2% iodine + 2.4% sodium iodide

• Saturated solution of potassium iodide (SSKI)has1g/mL • Clinical AE - parotitis

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Iodine / Iodophores / Iodides •  Iodine toxicity > > Iodide

•  Clinical: Caustic & Oxidant (Cytotoxic) •  Systemic (Acute)        

•  GI   (N/V & Pain)       •  Multiorgan

•  CNS with coma to seizures          •  Metabolic acidosis (Many causes

including ê clearance of H+; Not é Lactate)         

•  Hemolytic anemia          •  Hyperthyroidism          •  Secretions é all around          •  Respiratory, Renal, CV Crash         

Can see much é I- blood levels

with topical Irrigation of open wounds or mucosal surfaces

Iodine / Iodophores / Iodides

•  Laboratory è Iodide measured as Chloride • ê anion gap •  Diagnostic: ê anion gap + Acidosis        

•  Treatment: •  Dilute with Starch, Milk, or sodium thiosulfate

(May Δ Iodine to Iodide) •  Lavage?

•  Classically NO … b/c is caustic •  But it does è significant systemic symptoms

•  Observe for Caustic &/or Systemic injuries

Some Analyzers…

Question…

A classic approach to decontamination of phenol exposure?

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Phenols •  Found: •  Surface Disinfectant (Uncommonly used today) •  Fertilizers & Paints •  Chemical intermediary (Plastics) •  Campho-Phenique (4.7%), Chloraseptic (1.4%)

•  Sticky and Oily (Lipid soluble) è Excellent skin penetration •  Clinical:

•  Painless, Caustic (Burns) local effects (Coagulation Necrosis) èè Hypopigmented skin

•  Bradycardia and Hypotension •  CNS

•  Stimulant…Seizures •  Coma •  Tardive dyskinesia-like syndrome (Rabbit Syndrome – repetitive perioral movements)

Phenols •  No gastric emptying •  Charcoal absorbs phenol…but… Interferes with endoscopy

•  Ingestions, Ocular, Dermal è Dilution!!! •  Polyethylene glycol

•  Better than water in some (but not all) animal series (Is poorly soluble in water)

•  Vegetable (or any?) oil •  Water (…add Soap)

•  Start with it •  Problem: Spreads caustic agent to other skin

areas

(Low MW i.e. 300 or 400; Not

the high molecular

weight stuff used for WBI)

Substituted Phenols •  Hexachlorophene (pHisohex)

–  Less caustic than phenol…but… –  Premature infants washing (washing too much)

with 3% solution è Vacuolar Encephalopathy Cerebral edema

–  Neuro toxicity after ingestion •  Sodium octylphenoxyethoxyethyl

ether sulfonate and lanolin (pHisoDerm) –  Irritant –  Safe

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The ultimate home child cleaning Product...

Detergent Toxicity…

Soaps & Detergents •  Groups

•  Hand & Liquid wash soaps •  Automatic Dishwashing detergent •  Hard surface cleaners •  Scouring powders / Liquids •  Enzyme containing cleaners (proteins)

•  Soap: Salt of a fatty acid (An alkali + fat/oil) •  Detergent

•  Defined: A non-soap cleaner •  Includes Surfactants & Builders

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Detergents •  Surfactants (êsurface tension è wetting)

•  Anionic…. common •  Nonionic .. common •  Cationic … Problem

•  Builders (Water softeners) •  Inorganic salts ècleaning in hard water (by binding Ca++ / Other metals)

•  Alkaline (High concentrations è Corrosive) •  Granular (Automatic Dishwashing Detergent) •  Silicates & Carbonates (Common) •  Sodium phosphates (gone since 1970s)

Irritants è Minor GI upset Rx: Dilution

Detergents

•  Classic Examples •  Sodium laurel sulfate & other sulfates •  Dodecyl trimethyl ammonium bromide •  Dioctyl sodium sulfosuccinate

•  #1 Occupational problems - Contact Dermatitis

•  Quaternary amines è Dermal hypersensitivity Respiratory hypersensitivity

Anionic

Cationic Detergents •  Types

•  Quaternary ammonium amines Benzalkonium chloride – classic (Infrequent today)

•  Pyridinium compounds •  Corrosive if > 7.5%

•  Severe GI distress •  Pulmonary edema •  Ocular damage •  Hypotension

•  Treatment: Dilution/irrigation

• Automatic Dishwashing detergents • Disinfectants • Fabric softeners (low conc)

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Question...

Do you lavage a hydrogen peroxide

exposure?

Hydrogen Peroxide •  Two toxicities: (1) Irritant/Caustic (2) Gas formation

•  Ocular exposure è Irritation •  Treatment:

•  Dilution/irrigation •  Consider nasogastric aspiration if recent exposure

Percent Injury Gas from 1 mL CCs Household 3-9% Irritant 10 mL GI, N/V Bleaching Agents 35% Caustic 100 mL Rocket Fuel 80-90% Industrial > 10% Caustic 100 mL GI pain,

Air embolism

Hydrogen Peroxide

•  Local Tissue Injury •  Low concentration – Usually irritation alone, but has è

Ulcers & Hematemesis •  Subcutaneous Emphysema – from wound irrigation with 3%

solution •  Portal Gas…even with 3% solutions (Rare when is low

concentration) •  Oxygen Embolization

•  Cerebral infarction •  Mesenteric infarction

•  Acute Colitis – After 3% Colonic Enemas

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…and another cleaning group “I promise to never

ask for a raise, again!!!” said the

fellow to the program director

Chlorhexidine (4%, Hibiclens)

•  Poor enteral or topical absorption •  Low toxicity in general •  Contact Dermatitis (up to 8%) •  Anaphylaxis – Rare with dermal use

Potassium Permanganate (KMnO4) •  Uses Old: abortifacient, irrigant •  Current: Dermal antiseptic…eczema •  Strong oxidizer •  Poorly absorbed…but my be… Life

Threatening (Liver, Renal, CV ê Hemolysis, Pancreatitis, DIC)

•  Manganese Toxicity •  Chronic exposure •  Behavioral change, Hallucinations, Parkinsonism

KMnO4 + H2O èKOH + MnO2 + O2

Caustic Brown/Black

staining of tissues

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Formaldehyde

•  H2O soluble, highly reactive gas •  Formalin – Formaldehyde (37%) + Methanol

(12-15%) •  Potent Caustic •  Ingestion

•  Local tissue injury •  Metabolic Acidosis … Due to both tissue

injury & Formic Acid metabolite

•  CV collapse …death with 30-60 mL formalin ingestion •  Methanol - up to 40 mg/dL…but no blindness found

Toxic House ���Medication Topics

Gastrointesinal •  Anti-Diarrheals •  Anti-Emetics •  Acid Meds •  Laxatives •  Pro-Motilics

Antidiarrheal Meds Three Classes •  AntiMotility agents (Opioids)

•  Diphenoxylate •  Loperamide

•  Intraluminal agents •  Silicates •  Bulk-forming fibers •  Agents that alter

microflora •  AntiSecretory agents

•  Somatostatin •  Octreotide

The Focus

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Diphenoxylate •  Derived from meperidine (water insoluble) •  Rapidly absorbed •  Metabolite: Diphenoxylic acid is 5 Xs more active &

twice serum half-lifeè (Classic problem: Delayed toxicity)

•  Combined with atropine in Lomotil •  Onset: Avg 4.5 hrs (Range: 1-8 hrs) •  Toxicity: ~ 50% Anticholinergic

100% Opioid effects •  Be aware of

–  Delayed onset Opioid effects –  Duration of 24 hrs

Does Narcan work?

Yes; but only on the opioid effects

Loperamide •  Derived from diphenoxylate è Further ê in

opioid side effects •  40% absorbed, but < 1% becomes systemic •  Poor CNS penetration •  Most toxicity due to old concentrate •  Large safety profile •  Toxicity: Coma, N/V, Abdominal pain,

Constipation Rare: bradycardia, apnea

•  Reversed with naloxone

Other Opioids

•  Paregoric (Camphorated Tincture of Opium) •  Morphine (0.4 mg/mL) •  Essential oils •  Benzoic Acid •  Ethanol (45%) •  Glycerol

•  Tincture of Opium (Deodorized Tincture of Opium; Laudanum; Sometimes called “Paregoric”…not good) •  Morphine (10 mg/mL) •  Confusion between this and above…Overdose!

Greek paregorikos for soothing or

encouraging words

Camphor for taste

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Anti-Emetics

AntiEmetics •  Phenothiazine meds

•  Promethazine (Phenergan) •  Prochlorperazine (Compazine)

•  Butyrophenones

•  Ondansetron (Zofran) •  Mechanism: 5-HT3 antagonism •  90% metabolized via CYP •  Rare AEs: EPS, akathisia, HA •  Also èê Gut Motility (Anti-Diarrhea) •  Also – QT é

•  Metoclopramide (See Promotilic section)

NMS Temp Reg ↓ Anti-Everything •  Dopa (EPS) •  Muscarinic •  Alpha •  Histamine •  Membrane

(QRS, QT) •  Awake

Stomach Acid Meds

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Acid Meds: H2-Blockers

• Acute Overdose •  Generally benign •  Drowsy, Dizzy, Slurred, Confused, •  H2 Rs in Heart (? è rare Bradycardia & ê BP in OD)

• Adverse Effects: •  HA, Tired, Dizzy, AMS (elderly), Diarrhea/Constipation [Cimetidine]

•  Rare: Platelets , Hepatitis, Vasculites, Involuntary movements [Ranitidine]

•  Antiandrogenic (Gynecomastia, galactorrhea, Impotence) [Cimetidine]

Histamine Caffeine Cholinergics Food

H2 Receptors in Gastric parietal cell

Acid Secretion

Acid Meds ���Proton Pump Inhibitors

•  ProDrug (Weak Base) è Accmulates in acidic spaces (Secretory canaliculus of gastric parietal cell)èPronated in acid area; becomes activatedèBinds H+K+-ATPase è Irreversible Inhibition of Acid secretion

•  Mechanism is key because is the “final common path” •  Highly protein bound and very large VD •  Time Onset varies with pKa

(Rabeprazole with higher pKa and thus activated at higher pH)

•  Metabolism CYP 2C19 and 3A4 (…but few Drug interactions)

Esomeprazole (Nexium) Lansoprazole (Prevacid) Omeprazole (Prilosec) Pantoprazole (Protonix) Rabeprazole (Acephex)

Acid Meds ���Proton Pump Inhibitors

•  Adverse Effect: Diarrhea (bowel alkali è Flora Δ) •  Altered Absorption of Meds due to alkaline stomach

•  Griseofulvin •  Ketoconazole, Itraconazole •  Iron

•  Acute Overdose è Minor effects

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Acid Meds���Antacids

•  Gastric pH increased •  Altered GI motility (Mg è diarrhea; Al è constipation) •  Alter absorption by creating insoluble compounds •  Aluminum •  Magnesium •  Sodium •  Calcium

Few Adverse Effects Little Toxicity

Acute Overdose •  Osmotic Diuresis

è Fluid & Electrolyte Loss •  Hypermagnesemia

Acid Meds ���Antacids Systemic toxicity:

•  Chronic Use •  Renal Function ê

Accumulation Calcium è Stones, Bones,

Abd. Groans Aluminum è Bone Resorption

& Encephalopathy Magnesium èêDTR; êHR, êBP Weak, Nausea

Depletion Phosphate

Acid Meds ���Antacids

Milk-Alkali Syndrome •  Triad

•  Hypercalcemia •  Alkalosis

(èCa++ precipitationè ARF) •  Renal Impairment

•  Due to combined ingestion of: •  Absorbable alkalinizing agent (Sodium

Bicarb or Calcium Carbonate) •  Calcium

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Acid Meds���Misoprostol

•  Prostaglandin analog (PGE1) è •  Acid secretion ê •  Uterine Contractions ↑ •  Mucous and bicarb ↑ •  Dilate blood vessels

•  Adverse Effects •  Diarrhea (5-13%) and cramping (17%) •  Headache, Fatigue, Dizzy, •  Uterine bleeding & Rupture (Abortifacient) •  Deaths due to uterine complications and

Fetal Deaths due to delivery

Pregnancy Category X

Laxatives

Latin laxātus, to relax,

Laxus- loose

Laxatives Bulk •  Mechanism: Fiber retains fluid in colon •  Onset: Many hours – to - Days •  Most gentle group •  Examples – Fiber!

Agar Methylcellulose (Cetucil) Bran Psyllium (Metamucil)

Lubricant (no change in peristalsis) •  Next in strength •  Causes water & oils to penetrate stool •  Docusate (Colace) •  Mineral oil (Big use èê Absorption of fat-soluble Vit’s)

Proteins from Plantago ovata

…allergic reactions occur

Upset Tummy

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Laxatives Osmotic •  Onset: Days •  Examples

•  Glycerin •  Lactulose •  Sorbitol

Saline Osmotic •  Onset: 1-6 hrs (High – to - low dose) •  These increase intestinal volume which thus stimulates

peristalsis •  Examples

•  Magnesium citrate •  Magnesium hydroxide (Milk of Magnesia) •  Magnesium sulfate (Epsom salts) •  Sodium phosphate

Beware of electrolyte Hell…

Dehydration and Electrolyte Hell…

These é motility indirectly; by é gut volume and then motility starts up

Laxatives��� Anthraquinones

•  Naturally occurs in some plants Fungi, Lichens, and Insects

•  Serves as a basic skeleton for their pigments •  Natural derivates have stimulant laxative effects. •  Mechanisms

•  Gut Prostaglandins è Secretion and motility ↑ •  Inhibit colon Na+-K+ ATPase èê Na+ absorption •  cAMP ↑ secretion of Cl- and K+ & ê Na uptake •  Nitric oxide synthase è Fluid secretion ↑ •  Damaging mucosal cells

•  Onset: 6-8 days Supportive care and Discharge

Laxatives���Anthraquinones

• Aloe (Aloe vera) • Cascara (Buckhorn) • Phenolphthalein • Bisacodyl • Senna pods (Cassia alexandrina)

• Rhubarb root (Rheum palmatum)

Fixed drug eruption & Carcinogenicity (and thus going

bye-bye…)

Hydrolyzed by pancreatic lipase into glycerol and ricinoleic acid (anionic

surfactant) è peristalsis

Anthraquinone

Senna èRed / Brown Urine

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Laxatives: Acute Overdose •  Stimulants

•  N/V & Abdominal cramps mostly •  Dehydration and electrolyte changes unusual •  Massive phenolphthalein è Shock, pulmonary edema,

metabolic acidosis, Multisystem failure •  Saline / Osmotic

•  Phosphate •  Sxs of Hypocalcemia •  Bad Sxs è QT ↑, Cardiac arrest

•  Magnesium •  Kidneys usually save you •  Massive OD Problem •  CNS and Respiratory depression

Laxatives: Chronic Abuse •  Dehydration •  Hypokalemia •  Cathartic Colon

•  Atrophic mucosa & Atony •  Colonic musculature ê

•  Psuedomelanosis coli •  Anthraquinones è Damage mucosal

cells → Macrophage uptake è Form dark brown pigment (melanosis coli) within intestinal wall

•  Harmless •  Mostly clears w/i 1-year of stopping

Dehydration è Na+ loss è Aldosterone èé Na+ & Water resorption from the colon & ↑ K+ secretion è Hypokalemia

Promotilics

“Can you account for your movements?”

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ProMotilics (Prokinetics) Metoclopramide •  5-HT3 Agonist èé Motility •  It é Lower esophageal tone •  Adverse Events

•  No dose-related deaths •  EPS: Dystonias, Tardive Dyskinesia!!! •  NMS!!! •  Acute OD è Somnolence •  Hematologic Events

•  MetHemoglobinemia (therapeutic or OD) •  Neutropenia, Leukopenia, Agranulocytosis

Bethanechol •  Muscarinic agonist èéContractions •  Quaternary amine

D2-Antagonist

ProMotilic: Cisapride •  Introduced 1993; Pulled later •  Metabolism: 3A4 to an active, renally eliminated item (Parent

compound NOT renally eliminated) •  Actions: 5HT4 è Gut Smooth Muscle Activity Blocks K+ channels è Muscle Depole

•  No dose-related deaths •  Acute Overdose Mild GI effects •  Adverse events: HA, Diarrhea, Nausea, Abd. pain •  The QT Issue

•  QT è Torsades and Death

•  Related to CYP 3A4 meds (Inhibitors)

Monosodium Glutamate (MSG) •  Flavor Enhancer…classically associated with Chinese Food and meats

and poultry. •  Onset: 10-20 min •  Not immune related; 1-2% people affected •  Self Limited •  Clinical

•  Headache, a burning sensation on the back of the neck, chest tightness, nausea, diarrhea and sweating

•  Palpitations •  Bronchospasm •  Hypotension •  Numbness & Weak & Dizzy

•  Treatment - Beta agonists (?)���

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Nitrates •  Routes of exposure include MM, intact skin, lung •  Used to preserve foods, however, most comes to us via vegetables

that have been fertilized. Used has decreased much •  CLIN/PATH:

•  Vasodilation è HA, dizzy, N/V, SOB •  Withdrawal Vasospasm; occurs when away from the nitrate

intense work environment. Affects any person. Bad clinical outcomes have included MI

•  Met-hemoglobinemia •  Dermatitis •  Cataracts, sensory neuropathy, joint pain •  Converted to Nitrites in our body •  Group 2A: Probably carcinogenic to humans ���

Sulfites

•  Preservatives in wine, salad bars, fruit, juice, shrimp.

•  Is immune related. •  Onset in minutes •  Population: 5-10% w/ RAD get ill •  Clinical

•  Anaphylaxis (Rare) •  More common: chest tightness, bronchospasms hives, stomach

cramps, diarrhea,

Azo Dyes & Yellow Dye #5 (Tartrazine)

•  Azo compounds are compounds bearing the functional group R-N=N-R‘

•  Aryl azo compounds è vivid colors (reds, oranges, and yellows)

•  Azo dyes derived from benzidine are carcinogens (IARC I for bladder cancer)

•  Tartrazine •  synthetic lemon yellow azo dye used as a food coloring •  It causes the most allergic and intolerance reactions of all the

azo dyes, especially in asthmatics and those with an aspirin intolerance

•  Clinical Sxs •  Urticaria, angioedema, bronchospasm

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Artificial Sweeteners Acute Effects Chronic Effects

Aspartame

Headache, dry mouth, dizziness, mood change, nausea, vomiting, reduced seizure threshold, thrombocytopenia

Lymphomas, leukemias in rats (IARC – Not listed at all)

Saccharine Nausea, vomiting, diarrhea

Cancer in offspring of breast-fed animals, low birth weight, bladder cancer, Hepatotoxicity (IARC Group 3: Not classifiable as to its carcinogenicity to humans)

Mothballs •  Camphor: Not used now (Cinnamomum camphora, very lipid soluble, Seizures)

•  Naphthalene & Paradichlorobenzene Also: Toilet bowl & diaper pail deodorizers

•  Toxicity: •  Both è GI upset; N/V •  Napthalene

•  Toxicity infrequent but 1 ball has è Hemolysis •  Hemolysis & Met-Hemoglobinemia •  Sxs – Within 1-2 days; Anemia worst at 3 days •  G6PD deficiency èé Risk •  Treatment:

•  Ipecac if early; Charcoal ? •  Transfuse; Methylene Blue

Paradichlorobenzene #1 Used today Fairly benign

How do you know the type of mothball it is?

•  Concentrated salt solution (3 tbls in 4 oz. Water): •  Floats è Napthalene •  Sinks è Paradichlorobenzene

•  Sensation •  Drier - Naphthalene •  Oily – Paradichlorobenzene

•  X-Ray •  Faint / Not opaque Naphthalene •  Radio-opaque with Paradichloro.

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Diethyltoluamide (DEET) •  Classic Mosquito Repellant •  Concentrations vary from 5-100% (thus tough to assess)

•  Large safety margin •  Absorb: 5-15% (topical) •  Peaks: 1-2 hours •  Clinical

•  Similar with topical or ingestion •  Prodrome: Restless, Slurred, Ataxic •  Seizures & Coma (Occurred w/ 2 uses of 90% concentration)

•  Disposition: Symptoms within 2 hours

Radon (222Rn) •  Heaviest radioactive noble gas •  Product of the natural decay of uranium & thorium •  Largest component of background radiation – enters homes

via cracks in building structures

Radon •  Has short T ½ ~ 4 days èProblem if forms solid daughter

isotopes while in respiratory space èdeposits on respiratory tissues è Emit α particles as they decay

• é incidence of lung cancer (IARC I) •  (EPA estimates 21,000 deaths/yr) •  Avoidance:

•  Ventilate enclosed spaces •  Detectors, don’t smoke

•  Some areas of the country have higher concentrations such as new York, New Jersey, and Pennsylvania.