TOXICOLOGY HAND-OUTS PART 2 INSTRUCTOR: RALPH EPHRAIM S.

PALABRICA

TOXIN ELIMINATION

A. Forced Diuresis

B. Extracorporeal Methods

1. Hemodialysis

Diffusion – movement of solute particles from an area of higher solute concentration to a lower solute
concentration.

Indications for Hemodialysis:

• Acidosis (severe)
• Electrolyte imbalance (refractory hyperkalemia)
• Intoxication (salicylates, lithium, methanol, ethylene glycol)
• Overload (volume)
• Uremia (bleeding, altered mental status) Dialyzable Toxins

Water soluble:
• Volume of distribution <1L/kg
• Protein binding < 50% • MW < 500 Da

2. Hemoperfusion

Non-Dialyzable Toxins

• Lipid soluble
• Volume of distribution >1L/kg
• Protein binding ≥ 50%
• MW ≥ 500 Da

3. Peritoneal Dialysis • Only 10-15% as effective as hemodialysis.

III. INDUSTRIAL AND HOUSEHOLD TOXICANTS

Ethylene glycol
• Antifreeze preparation in car radiators, coolants, deicers
• Common in industrial solvents, detergents, corrosives, lacquer and paints
• Clear, odorless liquid

Treatment:

• Ethanol: competitive inhibition

• Fomepizole: 94-methylpyrazole: alcohol dehydrogenase inhibitor
• Vitamin B1 and B6

Methanol
• Colorless liquid, volatile at room temperature
• Common component of gasoline, antifreeze, perfume, wood alcohol, paint solvents, household cleaners

Treatment:

• Ethanol
• Fomepizole
Aldehydes

Formaldehyde (Formalin)
• Colorless liquid with pungent odor
• Embalming fluid, used in cosmetics, deodorants, detergents, dyes

Presentation Local effects:

mucosal irritation → oral, pharyngeal, conjunctival Metabolic acidosis (Bleeding).

Hydrocarbons

Hydrocarbon and Petroleum Distillates

Presentation:
• Burning sensation, cough
• Pneumonitis, atelectasis
• Benzene: blood dyscrasias
(acute myeloblastic leukemia, hairy cell leukemia)
• Chlorofluorocarbon, butane:
potentiate epinephrine effects → arrhythmia

Treatment:
• Mineral oil: to increase viscosity and ↓ risk of aspiration
• O2 support
• β2-agonists

CYANIDE

Sources:
• Prunus sp. (almond, cherry, apple), cassava, lima beans → cyanogenic glycosides
• Silver jewelry cleaner (SJC)

MOT: inhibits cytochrome oxidase

Presentation:

• CNS and CVS disturbances

• Respiratory depression

Treatment:

• Cyanide Kit
• Amyl nitrite (inhalational) + NaNO2 (IV) → methemoglobinemia + CN → cyano methemoglobinemia + NaS2O3 →
SCN (relatively nontoxic, more polar)
• Hydroxocobalamin → Cyanocobalamin

HYDROGEN SULFIDE
• Highly toxic, colorless gas with rotten egg odor
• MOT: inhibits cytochrome oxidase
Presentation:
• Irritation of mucous membranes
• Respiratory depression
ACIDS AND ALKALI

Acids:

corrosive → coagulation necrosis → forms protective eschar → less penetrating

Alkali:

caustic → liquefactive necrosis → more penetrating

Treatment:
• Wash with amount of running (tap) water 30 minutes
• For acid ingestion: give egg whites

PHENOL

• Carbolic acid
• Component of industrial paint removers
• Once widely used as antiseptic (Joseph Lister)
• MOT: protein denaturation

• Presentation:
• Tingling sensation/ numbness (local aesthetic effect)
• White discoloration of the skin → corrosive burns

• Treatment:
Dilute
• Wash with amount of running (tap) water 30 minutes
• For acid ingestion: give egg whites

FOOD ADDITIVES

Tartrazine (FD&C 5) & Monosodium Glutamate

Treatment: Epinephrine, Antihistamines

IV. HEAVY METALS AND CHELATING AGENTS (CALMIC)

1. Cadmium
2. Arsenic
3. Lead
4. Mercury
5. Iron
6. Copper

Common MOT: bind to –SH group of enzymes → inactivation

• Treated with the use of Chelators/ Chelating agents
• Forms water-soluble complexes with heavy metals
→ easily excreted
• BAL DMSA
• Deferoxamine
• Penicillamine
• CaNa2 EDTA
ARSENIC

• Lewisite metal
• Salvarsan, Compound 606, Arsphenamine

Presentation

Acute
• Garlic odor breath
• Diarrhea, dehydration
• CNS: delirium, seizure, coma

Chronic Treatment: BAL if severe + Penicillamine

• Mee’s lines: white line cross the nails of fingers/ toes
• Milky/ rosy complexion
• Keratosis
• Hair loss
• Abnormal weight gain

LEAD

• Component of:
-leaded paints, newsprint,
automobile exhaust, earthenware
• Half-life (t ½):
• Bones: 32 years
• Kidney: 7 years
• MOT: inhibits enzymes in heme synthesis
• ALA dehydrogenase: important for lab diagnosis
• Ferrochelatase

Treatment:
• BAL
• CaNa2 EDTA
• DMSA

CADMIUM

• Component of anti-dandruff shampoos, stink bombs, batteries

• MOT: binds to bone (compete with Ca) → distortion of bone structures
MERCURY

• Quicksilver
• MOT: Inhibits monoamine oxidase (MAO)

Forms

Inorganic:
HgCl: calomel
HgCl2: corrosive, sublimate, bichloride of mercury

Organic:
Thimerosal: Merthiolate®
Methylmercury: bioaccumulate and bioamplification in fishes.

IRON

• Usual cause of toxicity is ingestion of OTC preparation by children

• MOT: has corrosive effects in the GI bleeding

Treatment: Deferoxamine (Desferal® )

COPPER

• Toxicity usually occurs in Wilson’s disease

• MOT: binds to hepatic enzymes and
serum proteins → free radicals → hepatotoxicity and nephrotoxicity

Presentation
• Liver and Kidney failure
• Kaiser-Fliescher rings: Copper deposits on corneal limbus

Treatment: Penicillamine (Cuprimine®)