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 30-90 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

30-50mg/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 - 12 -14 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 - 24-72 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 0.5 - 1 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 200 - 400 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