Toxicology - University of Kentucky



Toxicology

Cosmetics generally safe (exceptions are wave neutralizer [boric acid] an nail products [acetonitrile, methacrylic acid, nitromethane)

Cleaning substances toxic when concentrated (Drano contains 54% NaOH)

Plants are variable (Philodendrons contain calcium oxylate crystals causing pain, Foxglove contains digoxin causing side effects)

Pharmaceuticals DUH!, most frequent are analgesics and cold/cough medicines, Pediatric fatalities often due to excessive iron intake

|Toxin |MOA |Effects |Treatment |Miscellaneous |

|Carbon Monoxide |binds to hemobglobin 240X stronger|tissue hypoxia, 30-50% HA, faint on exertion, |pure or hyperbaric oxygen |product of incomplete combustion shift oxygen dissoc. |

| |than oxygen |irritability, dizziness collapse; 60-70% cause ( HR, | |curve to left thus lowering partial pressure of oxygen |

| | |(CO, (RR, Pinkish skin discoloration | |availability to tissues, |

|Sulfur Dioxide |form acid w. contact mucous |increased mucous, bronchoconstriction |remove exposure and treat irritation| |

| |membrane | | | |

|Nitrogen Oxide | |pulm. edema, ENT irritation |reduce edema/inflam |from silage, gas/kerosene heaters |

|Ozone | |[low] = shallow rapid resp, (pulm compliance, [high] = |treat pulm edema and inflammation |prod by UV absorption by NO2 |

| | |pulm edema, bronchitis, (bronchoconstrictor sens | | |

|Arsenic |interacts with sulfhydryl groups |Acute = PAIN, corrosion of GI tract, bleeding, |supportive, Dimercaprol |colorless and tasteless, found in industry, herbicides,|

| |(pyruvate deh. in TCA cycle) |irritant, vomiting, “rice water” stool and death, | |insecticides, natural in ground water, burnt coal |

| | |Chronic = hyper-pig and -ker, cancer (skin, lung, | | |

| | |bladder), alopecia, BM depression, anemia | | |

|Cadmium |inhibits sulfur cont enzymes (esp.|Inhalation = Pulmonary edema + Nephrotoxicity, Oral = |Vitamin D, supportive, chelators |manufacturing, burnt fossil fuel, poorly absorbed from |

| |AAT) |osteomalacia via bad Ca/PO4 balance (bone pain) |ineffective |GI tract |

|Lead |bind sulfhydryl group (inhibit ALA|can replace Ca in bone (reversible), Acute = RARE, |EDTA, Dimercaprol, Penicillamine, |children, lead based paints |

| |dehydratase causing (heme |encephaloacolic, colic, Chronic = periph neuropathy, |Succimer (children), recommended | |

| |synthesis) |anemia, neurocognitive defects (children), growth |when conc >45 ug/dL | |

| | |retardation | | |

|Mercury |bind sulfhydryls, phosphoryl, |Acute = chest pain SOB, N/V, Chronic = CNS, tremors, |Penicillamine, Dimercaprol, ineff. |CNS and kidney are target organs, Methyl mercury is |

| |carboxyl, amide, amines |emotional fx, irritability, Mad Hatter syndrome |for methyl mercury |most toxic form |

|Iron |occur when Fe< binding cap of |corrosive on GI tract, ulceration, hemorrhage, coag |prevent additional absorption via |iron overload from vitamins (children), iron rapidly |

| |ferritin, |necrosis, (CO, shock, hepatic damage, bloody diarrhea, |ipecac induced emesis, gastric |cleared from plasma |

| | |tachycardia, hepatic failure, (SGOT, (SGPT |lavage, Deferoxamine | |

|Toxin |MOA |Effects |Treatment |Miscellaneous |

|Ethanol | |visual impairment, alcoholic ketoacidosis |symptomatic |preferentially metabolized in presence of Methanol |

|Methanol | |greatest acidosis of alcohols, glycols, or aldehydes, |Emesis, Lavage, Ethanol, Fomepizole |toxicity via metabolism to formaldehyde and formic |

| | |permenant blindness, metabolic acidosis, CNS depression |, Na-bicarb with major focus being |acid, ELEVATED ANION GAP ACIDOSIS |

| | |(euphoria, weakness, coma, convulsions), fixed dilated |correction of acidosis | |

| | |pupils, | | |

|Ethylene Glycol |( ox phos, (cell resp, and |Ca oxalate crystals damage tissues leading to pulm |Ethanol, Na Bicarb, hemodialysis, |toxicity via metabolism to oxalic acid, sweet taste, |

| |(glucose metab |edema, CHF, tachycardia, renal failure |Fomepizole |toxic doses as low as 100 mL, LARGE ANION GAP ACIDOSIS |

|Hydrocarbons |many |CNS depression, pneumonitis, edema, hemorrhagic |prevent aspiration |no emesis unless ingestion exceeds 1mL/KG or if |

| | |bronchopneumonia, | |contains metals, camphor, or insecticides |

|Atropine |Antimuscarinics |delirium, hallucinations, seizures, coma, tachycardia, |Physostigmine but not with TCAs, | |

| | |HTN, hyperthermia, mydriasis |control hyperthermia | |

|Cholinomimetics |OP inhibitors of AChE, Carbamate |Anxiety, agitation, seizures, coma, brady or |support respiration, Atropine, | |

| | |tachycardia, pinpoint pupils, salivation, sweating |Praloxidime | |

| | |(SLUD) | | |

|Opiods |Heroin, Morphine |Lethargy, sedation, coma, cool skin, bradycardia, |Naloxone, support respiration | |

| | |hypotension, hypoventilation, pinpoint pupils | | |

|Salicylates |uncouple ox phos |anion gap metabolic acidosis, lethargy, seizures, |alkalinize urine, potassium, Na | |

| | |hypokalemia, dehydration, hyperthermia |bicarb | |

|Sedatives-Hypnotics |Barbiturates, Ethanol, |hypotension, hypothermia, nystagmus, decreased muscle |Flumenazil for BDZ | |

| |Benzodiazepines |tone | | |

|Stimulants |Cocaine, Amphetamines |ANS modulation (vasoconstriction, myocardial |control seizures, BDZ, control |myocardial toxicity treated with hypertonic Na bicarb |

| | |stimulation), ventricular arrythmias and hypotension |hypterthermia | |

|Tricyclic Antidepressants |Fast Na channel block, (inotropism|widened ORS complex, CCC (coma, convulsion, |Diazepam (seizures), Phenytoin | |

| | |cardiotoxicity |(arryth) | |

|Acetaminophen |NAPQI reactive intermediate forms |No immediate effects short of N/V and malaise, |N-Acetyl Cysteine |reduced GSH primary reason for toxicity |

| |adducts |Hepatotoxic w. death in 7-10 days | | |

Anion Gap (for this class) is (Na + K) – (HCO3 + Cl) which should normally be 12-16 meq/L

Treatment of Intoxication

Chelators bind and stabilize metals, are water soluble (Renal excretion), often administered in Ca form (since will complex endogenous Ca)

|Drug |MOA |Use |Side Effects |Miscellaneous |

|Dimercaprol |chelator |acute Arsenic and Mercury, NOT Cadmium and Iron |tachycardia, HTN, N/V, ( PT |not cure neurological effects, Parenteral admin |

|Calcium Disodium Edetate (CDE)|chelator |Iron, Lead, Zinc |Nephrotoxicity (avoid in RTN) |IV admin, minimize toxicity with hydration and ................
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