the toxic house kleinschmidt - acmt€“ neuro toxicity after ingestion • sodium...
TRANSCRIPT
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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.