Alcohols, Aldehydes and Ketones

Introduction 3 most common alcohol poisonings are: ethanol, methanol and isopropanol. Alcohol ingestions account for 14/1000 hospital admins Up to 72% of trauma patients were + for alcohol in their blood 1998 ethanol accounted for 33,269 exposures reported to PCC, 973 were major toxicities and 42 resulted in death 1998, isopropanol, 19,301 reported, 83 major toxicity, 3 deaths 1998 methanol, 1041 reported, 24 major, 10 deaths

Introduction, cont. Acute intoxication with any alcohol may result in: –coma –death due to respiratory depression –CV collapse due to CNS depression –aspiration of vomitus Children under the age of 5 - have high incidence of exposure Recreational misuse very high among teens and young adults

Alcohols Ethyl alcohol - grain alcohol - C2H5OH Derived from fermentation of sugars in fruits, cereals and vegetables Present in aftershaves, colognes, perfumes, OTC meds, mouthwashes, and a myriad of alcoholic beverages Colorless, flammable, volatile liquid, toxin Proof = twice the per cent by volume; gun powder was soaked in an alcoholic beverage and ignited, if it exploded then it was “100 proof” is was at least 50% alcohol a direct CNS depressant - both motor and sensory

Ethanol, cont. Uses –preservative –solvent –vehicle for other drugs (tinctures, elixirs, spirits) –disinfectant –hardens the skin –cools the skin –injectable nerve block –stimulates appetite and aids in digestion

Ethanol Rapidly absorbed from stomach and sm intestine Peak levels reached in minutes post ingestion Metabolism by liver by alcohol and aldehyde dehydrogenases ethanol - acetaldehyde - acetic acid - C02 + H20 Primary source of ingested ethanol is alcoholic beverages Associated problems with ethanol ingestion: hypoglycemia, heqad trauma, carbon dioxide narcosis, hypoxia

Ethanol, cont. Metabolism - you metabolize about 1 drink/hr. –13-25mg alcohol/deciliter/hour –in alcoholics this rate increases to mg/dL/hr 12 oz. beer = 3 oz wine = 1 oz whiskey = 15 ml of ethanol New Texas State law has lowered legal limit to 0.08% (so 0.8 ml 90% ethanol/kg = 0.08% BAC)

To calculate BAC 1 ml 90% ethanol/kg BW gives BAC 0.1 % so for a 220 lb. Male convert to kg. 100 kg so 100 ml or approx. 3 1/2 ounces of 90% or 180 proof. New Texas Law = 0.08 so revised formula 0.8 ml 90% ethanol/kg BW = BAC 0.08%

Ethanol, cont. Short term effects - intoxication and mood alteration Long term effects –hepatic cirrhosis –esophageal cancer –pancreatic disorders –Wernicke’s syndrome –B vitamin deficiencies –malnutrition

Ethanol, cont. Alcohol should never be taken with other CNS depressants Treatment –keep patient from injuring themselves through falls, etc. –protect and maintain airway

Alcohols, cont. Methanol - methyl alcohol, wood alcohol Sources - no medicinal use, used in industry and cleaning fluids, solvents, paints, varnishes, Sterno Fuel, gasohol, windshield washer fluid (30-40% methanol), and “moonshine”, etc. Fatal dose is between 30 and 240ml Metabolism methanol - formaldehyde - formic acid - CO2 + H2O CNS depressant Profound metabolic acidosis and blindness

Methanol, cont. Formic acid inhibits cytochrome oxidase in the fundus of the eye –disrupts axoplasmic flow –axons swell causing visual impairment –edema of optic disc –degradation of formic acid is folate dependent Visual disturbances seen in 50% of cases of toxicity –blurred vision –yellow spots –snowstorm like vision –photophobia

Methanol, cont. Clinical presentation of ingestion –headache –vertigo –nausea, vomiting and diarrhea –painful, tender abdomen –colic and gastritis –dyspnea and tachypnea - Kussmaul’s respiration –ocular signs

Methanol, cont. Treatment of methanol ingestion –provide airway, breathing support –folic acid (potentiates the folate-dependent metabolism of formic acid to CO2 and H2O) –ethanol - tie up enzyme system –supportive care

Alcohols, cont. Isopropyl alcohol - rubbing alcohol (70% isopropanol) Second most commonly ingested alcohol Sources –rubbing alcohol, window cleaners, antifreeze, detergents, jewelry cleaners, solvents, disinfectants Ingestion typically seen in chronic alcoholics, children (can be secondary to inhalation or topical absorption from sponge baths) and suicide attempts Lethal dose is 240 ml Metabolized much slower than ethanol

Isopropyl alcohol, cont. Clinical presentation of ingestion –headache, dizziness –ataxia –nystagmus –abdominal pain, nausea, vomiting, hematemesis –patient is intoxicated but no smell of alcohol to breath (breath may smell fruity like acetone - Isopropanol metabolized to acetone by ADH)

Isopropyl alcohol, cont. Treatment –gastric lavage –activated charcoal –maintain airway –supportive care

Ethylene glycol Clear, colorless, odorless, viscous fluid with a bittersweet taste Sources - antifreeze (has fluorescein dye added to show leaks) About 500 cases reported a year in humans Ethylene glycol by itself is relatively non toxic but its metabolites are highly toxic ethylene glycol + alcohol dehydrogenase - glycoaldehyde + aldehyde dehydrogenase - glycolic acid - glyoxalate - oxalate (combines with calcium to form calcium oxalate crystals)

Ethylene glycol, cont. Basis of toxicity –lethal dose in an adult = 100 ml –tissue destruction - precipitation of calcium oxalate in tissues, especially in the renal cortex, brain, liver, lungs, blood vessels and pericardium –severe metabolic acidosis(glycolic acid)

Ethylene glycol, cont. Clinical presentation Phase I - 30 min - 12 hrs post ingestion, patient may appear inebriated, nauseated, vomiting, ataxia, no alcohol smell on breath Phase II hours later, tachycardia, elevated BP, pulmonary edema, tachypnea, cardiac failure, secondary to deposition of calcium oxalate crystals in the vascular tree, lungs and heart Phase III hours after ingestion, flank pain, costovertebral angle tenderness, oliguric acute renal failure

Ethylene glycol, cont. Diagnosis –drunk patient with NO alcohol smell on their breath –calcium oxalate crystals in the urine –clinical evidence of renal failure –Kussmaul’s respiration

Ethylene glycol, cont. Treatment –treat acidosis –ethyl alcohol (blocks metabolism of EG by binding ADH) –Thiamine (Thiamilate) - Vitamin B-1 is water- soluble and utilized in many cellular functions that involve energy formation and utilization. Promotes conversion of glyoxalate to a nontoxic metabolite, alpha-hydroxy-beta-ketoadipate. –water-soluble vitamin B-complex (a cofactor in conversion of glycolic acid to non-oxalate compounds)

Aldehydes Formaldehyde –Uses - adhesives for plywood and veneers and preservatives (formalin - 50% solution) –Irritating to mucous membranes Levels of PPM - detectable by odor 2-3 PPM - mild irritation 4-5 PPM - intolerable to most people –Levels of 1 PPM common in new homes

Formaldehyde, cont. Clinical presentation –runny nose –sore throat –headache –cough –drying and redness of skin –can cause cancer in mice and rats, no evidence of human carcinogenesis Treatment - give fresh air and wash off skin

Ketones Acetone –Sources - component of industrial glues, solvents, fingernail polish remover –Relatively non toxic - ingestion of ml may not be serious –Has a characteristic odor and narcotic like properties (CNS depressant) –Threshold limit is 1000 PPM for workers exposed to 8 hours/day

Acetone, cont. Clinical signs –with inhalation - cough, bronchial irritation, headache, fatigue –with ingestion - vomiting and nausea, metabolic acidosis, CNS depression (in severe cases) Treatment –give fresh air –give emetic –treat acidosis and maintain airway