Drug info - Isopropyl alcohol

[Pino]

Swim has some hesitation about asking this, he doesn't want people bringing on ideas, but swim grew too curious about it. Swim was wondered how poisonous isopropyl alcohol is. Swim isn't going to drink it and nobody should think about it. This is not meant as advice. It is purely theoretical interest. He doesn't like alcohol alike drugs, but he only read it is twice as poisonious as ethanol. That doesn't sounds too treating. And it is converted by the liver to acetone. He understood acetone can do quite a lot damage in the long term, but so does alcohol.

Can swim theoretically drink this safely? Swim knows the answer should be no, but he can't discover why. He has not the intention to drink it, nobody should.

[Paracelsus]

If I remember correctly (not in the mood to check my references now), many of the simple monohydroxylic alkyl alcohols have ethanol-like effects, but all are more toxic than ethanol.

I suspect that the danger lies in the toxicity of the breakdown products (methanol >> formaldehyde; ethanol >> acetaldehyde; isopropanol >> acetone, 1-propanol >> propionaldehyde; etc.).

I'm pretty sure that acetone is much more toxic than ethanol. Acetaldehyde is not too toxic, but still partly responsible for the damage caused by alcohol abuse.

[Pino]

Swim found this on emedicine.com. It seems more people figured out isopropyl alcohol is less toxic than methanol. It is the second most ingested alcohol it seems. On interesting thing swim found is the following:

• In 1998, ethanol accounted for 33,269 exposures reported to US poison centers, of which 973 (2.9%) resulted in major toxicity and 42 (0.1%) resulted in death.
• In 1998, isopropanol accounted for 19,301 exposures reported to US poison centers, of which 83 (0.4%) resulted in major toxicity and 3 (0.02%) resulted in death.
• In 1998, methanol accounted for 1041 exposures reported to US poison centers, of which 24 (2.3%) resulted in major toxicity and 10 (1%) resulted in death.

It seems that isopropanol causes less deaths than ethanol. This doesn't says anything about long term effects. Maybe this is because people are more worried about ingesting isopropanol alcohol.

Author: Ann G Egland, MD, Consulting Staff, Department of Operational and Emergency Medicine, Walter Reed Army Medical Center Coauthor(s): Douglas R Landry, MD, Consulting Staff, Department of Emergency Medicine, Sentara Bayside Hospital

Ann G Egland, MD, is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, Association of Military Surgeons of the US, Medical Society of Virginia, and Society for Academic Emergency Medicine

Editor(s): Jeffrey Glenn Bowman, MD, MS, Consulting Staff, Department of Emergency Medicine, Mercy Springfield Hospital; John T VanDeVoort, PharmD, Clinical Assistant Professor, College of Pharmacy, University of Minnesota; Michael J Burns, MD, Instructor, Department of Emergency Medicine, Harvard University Medical School, Beth Israel Deaconess Medical Center; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Asim Tarabar, MD, Assistant Clinical Professor of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Bibliography
Background: The 3 most common alcohol poisonings result from ethanol, methanol, and isopropanol (isopropyl alcohol). The devastating and potentially life-threatening toxicity that results from ingestions of any of these alcohols makes recognition of alcohol poisoning an essential part of emergency medicine.
Recognition of the morbidity and mortality that may result from ingestion of small quantities of methanol is particularly important. Ethylene toxicity is covered in a separate article (see Toxicity, Ethylene Glycol).

Pathophysiology: The organs that are most severely affected vary depending on the type of alcohol ingested.

Ethanol
Ethanol (ethyl alcohol) is an aliphatic alcohol present in aftershaves, colognes, perfumes, mouthwashes, over-the-counter (OTC) medications, and a myriad of alcoholic beverages.
Ethanol is a direct CNS depressant, which causes decreased motor function and decreased consciousness level. At high concentrations, ethanol is an anesthetic and can cause autonomic dysfunction (eg, hypothermia, hypotension), coma, and death from respiratory depression and cardiovascular collapse.
Ethanol is easily absorbed from the stomach and small intestine. When the stomach is empty, peak levels are reached 30-90 minutes after acute ingestion. When food is present in the stomach absorption is delayed. Total absorption may take as long as 6 hours.
Metabolism of ethanol is carried out in the liver by several enzymes, including alcohol dehydrogenase, aldehyde dehydrogenase, microsomal ethanol-oxidizing system (MEOS) or CYP2E1, and peroxisomal catalase. Most (90-95%) enzymes are metabolized by alcohol and aldehyde dehydrogenases. MEOS accounts for about 5% but may increase to 25% in the chronic drinker. Normally, catalase makes a small contribution to ethanol metabolism; its role is more significant at high serum ethanol concentrations.
Nonhabituated patients metabolize ethanol at 13-25 mg/dL/h. In persons with alcoholism, this rate increases to 30-50 mg/dL/h. Metabolism rates vary greatly between individuals and cannot be predicted. Similarly, because of tolerance, blood alcohol concentrations (BACs) must be interpreted in conjunction with history and clinical presentation. Some individuals with chronic alcoholism may have an almost normal mental status and neurological examination, yet have BACs of 400 mg/dL. Conversely, nonhabituated drinkers may show marked effects of intoxication at very low BACs.
Methanol
Methanol (methyl alcohol) is found in cleaning materials, solvents, paints, varnishes, Sterno fuel, formaldehyde solutions, antifreeze, gasohol, "moonshine," windshield washer fluid (30-40% methanol), and duplicating fluids.
A CNS depressant, methanol is potentially toxic in amounts as small as a single mouthful. When metabolized by hepatic alcohol and aldehyde dehydrogenase, methanol forms formaldehyde and formic acid, both of which are toxic. The eyes, CNS, and GI tract are affected. Formic acid is the primary toxin that accounts for the majority of the anion gap, metabolic acidosis, and ocular toxicity. Lactic acid also contributes to the anion gap.
Formic acid inhibits cytochrome oxidase in the fundus of the eye. Disruption of the axoplasm is due to impaired mitochondrial function and decreased ATP production. Swelling of axons in the optic disc and edema result in visual impairment. Degradation of formic acid is folate dependent. Thus, if a folate-deficient person ingests ethanol, toxicity may be more severe due to the increased accumulation of formic acid.
Approximately 90-95% of methanol metabolism occurs in the liver, while 5-10% is excreted unchanged through the lungs and kidneys. Methanol is primarily metabolized by alcohol and aldehyde dehydrogenase. Formaldehyde has a short half-life, lasting only minutes. Formic acid is metabolized much more slowly, and it bioaccumulates with significant methanol ingestion.
Isopropanol
Isopropanol is found in OTC rubbing alcohol (70% isopropanol), antifreeze, skin lotions, and some home cleaning products.
Death from ingestion of isopropanol is uncommon. Isopropanol has 2-3 times the potency of ethanol and causes hypotension and CNS and respiratory depression more readily than ethanol. Peak levels occur approximately 30 minutes after ingestion because of rapid GI absorption, which is delayed in the presence of food. Isopropanol is a CNS and cardiac depressant with about twice the potency of ethanol. Serum levels more than 400 mg/dL are potentially fatal.
Approximately 20-50% of isopropanol is excreted unchanged by the kidney, while 50-80% is converted in the liver to acetone, which is a CNS depressant in its own right. Acetone is excreted primarily by the kidneys, with some excretion through the lungs. The elimination half-life of isopropanol is 4-6 hours; that of acetone is 16-20 hours. The prolonged CNS depression seen with isopropanol ingestion is partially related to acetone's CNS depressant effects.
Frequency:

• In the US: In some studies, alcohol ingestions account for 13-14 hospital admissions per 1000 people. Ethanol is the most common alcohol ingestion. Acute intoxication is seen commonly in the ED. Other studies have shown that up to a third of all patients have detectable ethanol levels at ED presentation, irrespective of the chief complaint. Up to 72% of trauma patients had positive toxicology screen results; ethanol accounted for 55% of these findings.
• Methanol poisoning epidemics have occurred because of ingestion of contaminated "moonshine." The most notable was in Atlanta in 1951, when 90 gallons of illicit whiskey containing 35-40% methanol produced 323 poisonings and 41 deaths.
• In 1998, ethanol accounted for 33,269 exposures reported to US poison centers, of which 973 (2.9%) resulted in major toxicity and 42 (0.1%) resulted in death.
• In 1998, isopropanol accounted for 19,301 exposures reported to US poison centers, of which 83 (0.4%) resulted in major toxicity and 3 (0.02%) resulted in death.
• In 1998, methanol accounted for 1041 exposures reported to US poison centers, of which 24 (2.3%) resulted in major toxicity and 10 (1%) resulted in death.

• Internationally: More recently between 2002 and 2004, a total of 51 patients were admitted to the hospital in Norway with methanol poisoning, with 9 in-hospital deaths and 8 out of hospital deaths.

Mortality/Morbidity: Acute intoxication with any of these alcohols may result in coma or death due to respiratory depression and cardiovascular collapse subsequent to CNS depression.
Poor outcomes have been associated with acidosis, hypotension, or coma at presentation.

• Ethanol, when used chronically, affects multiple organ systems.

• Methanol ingestion may cause blindness.

• Isopropanol may cause severe GI hemorrhage, hemolytic anemia, and refractory hypotension.

Age: Alcohols are the most common accidental toxic ingestions by children younger than 5 years. However, because of deliberate ingestions (eg, suicide attempts, recreational use/misuse), toxic ingestions may occur at any age.

r Information Introduction ClinicalDifferentials Workup Treatment Medication Follow-up Miscellaneous Bibliography
History: Humans have a long history of ingesting alcohols. Ethanol is the most common deliberate ingestion of this toxic substance. It is a component of a wide variety of beverages that are consumed nearly worldwide.

• Ethanol

• • Alcoholic beverages are the primary source of ingested ethanol. Other sources include colognes, perfumes, mouthwashes, medications, and aftershave lotions.

• • Ethanol may be ingested accidentally, as often occurs in children, or deliberately, as by the patient with alcoholism or for recreation.

• • Ethanol may be associated with other causes of altered mental status (eg, hypoglycemia, head trauma, mixed ingestions, post-ictal state, carbon dioxide narcosis, hypoxia, infection, hepatic encephalopathy). Consider these conditions when evaluating the patient with known alcohol ingestion.

• Methanol

• • Methanol ingestion may result in serious consequences, including blindness and death. A delay in treatment may lead to increased morbidity and mortality. Recognition and timely treatment are essential for a full recovery.

• • Methanol commonly is found in numerous compounds, including solvents, photocopy inks and diluents, paints, varnishes, antifreeze, gasoline mixtures (eg, gasohol, "dry gas"), canned heat (eg, Sterno), and even wines (as a byproduct of the natural fermentation process). One study of 11 patients seen between 1995 and 1997 identified 8 patients who had ingested windshield wiper fluid, one who drank gas-line antifreeze, and 2 patients with the source unknown.

• • Toxicity most commonly ensues following accidental or intentional ingestion. Toxicity also may occur following inhalational exposure. Inhalation may be accidental (eg, industrial settings), or it may be deliberate (eg, volatile inhalant abuse, as in "bagging" or "huffing" solvents for their inebriant effects). Transdermal or respiratory tract absorption also may cause toxicity.

• • Following ingestion, methanol is rapidly absorbed from the GI tract. Peak levels occur within 30-90 minutes of ingestion.

• • Methanol is predominantly metabolized in the liver by hepatic alcohol dehydrogenase. At low serum concentrations (<20 mg/dL) and during hemodialysis, methanol elimination is quick and first-order, with an elimination half-life of about 3 hours. At higher serum concentrations, methanol elimination is slow and zero-order, at 8.5 mg/dL/h. Thus, following large doses, methanol is metabolized and eliminated very slowly. Duration of the latent period (time from ingestion until clinical toxicity is evident) is highly variable. Latent periods of 40 minutes to 72 hours have been reported; in most cases, onset of toxicity manifests in 12-24 hours. Co-ingestion of ethanol increases both the latent period (40-50 h) and elimination half-life.

• • Approximately 50% of patients report visual disturbances. These disturbances usually are described as blurry, indistinct, misty, or snowstormlike. Patients also have reported yellow spots, central scotomata, and photophobia.

• • CNS complaints include headache and vertigo. GI complaints may include nausea, vomiting, and abdominal pain due to direct irritation.
  • Complaints do not correlate with the amount or severity of the ingestion.

• Isopropanol

• • Isopropanol is the second most commonly ingested alcohol. The most common source is rubbing alcohol (70% isopropyl alcohol). Other sources of isopropanol include window cleaners, antifreeze, detergents, jewelry cleaners, solvents, and disinfectants.

• • Ingestions typically occur in alcoholic patients, children, and those who attempt suicide. In children, exposure also may occur from inhalation or topical absorption (eg, sponge bath).

• • CNS complaints include headache, dizziness, poor coordination, and confusion. GI complaints include abdominal pain, nausea, vomiting, and gastritis with hematemesis.

• • Patients appear intoxicated but do not smell like ethanol; however, they may have the fruity odor of acetone.

• Obtaining a history of the substance and quantity ingested is important. The physician may need to acquire the history from emergency medical services (EMS), parents, relatives, or friends accompanying the patient. Consider other differential diagnoses for altered mental status, as more than a single cause may be present.

Physical: Alcohol ingestions may present in somewhat similar manners. An alteration in mental status is seen with all of the alcohols, given the ingestion of a sufficient quantity of the substance. This alteration may be present to varying degrees depending on the patient.

• Ethanol

• • Clinical presentation depends on BAC and tolerance to ethanol.

• • The patient may have a flushed face or diaphoresis and may be agitated or ebullient and loquacious due to early disinhibition. This condition may progress to ataxia, slurred speech, drowsiness, stupor, or coma. Nystagmus (horizontal) commonly is observed.

• Methanol

• • Ocular physical findings include sluggishly reactive or fixed and dilated pupils. Visual field constriction also may be present. Retinal edema or hyperemia of the optic disc may be seen. Optic atrophy may appear in late stages (permanent blindness). Visual symptomology can occur without visible funduscopic changes. Visual acuity often is abnormal.

• • CNS signs include lethargy and confusion. Patients also may present in a comatose condition or with seizures. Cases have been reported of putaminal and cortical necrosis observed on MRI of patients surviving methanol ingestion. Neurologic sequelae (eg, parkinsonism, optic atrophy, focal cranial nerve deficits) have been described.

• • Respiratory signs include dyspnea (rare cases) or even Kussmaul respiration, despite acidosis. Cardiac signs (eg, hypotension, bradycardia) are late signs associated with a poor prognosis.

• • The patient may have severe abdominal tenderness.

• • Death usually is due to abrupt cessation of respiration. Until that endpoint, cardiovascular status is generally well maintained.

• Isopropanol

• • Nystagmus or miosis may be observed.

• • The patient usually appears intoxicated but smells of acetone instead of ethanol.

• • Sinus tachycardia may be present, but examination usually reveals no other cardiac dysrhythmias.

• • Isopropanol is a GI irritant that causes abdominal pain, nausea, vomiting, and gastritis with hematemesis.

• • Severe ingestions may result in coma, respiratory depression, and hypotension secondary to vasodilatation and negative cardiac inotropy. Loss of deep tendon reflexes (DTRs) also may be observed.

• • In rare cases, myoglobinuria, acute tubular necrosis, hepatic dysfunction, and hemolytic anemia may occur.

[Paracelsus]

The overall impression is that isopropanol is more potent and much more toxic than ethanol.

Some translations for readers which may start to think that isopropanol isn't that bad:

* hematemesis = puking blood
* hepatic dysfunction = liver failure
* myoglobinuria = indicates rhabdomyolysis (destruction of muscle tissue followed by kidney failure)
* acute tubular necrosis = indicates kidney failure; dead tissue gets into urine

Not quite fun.

Reputation Comments on this post:

Tnx, that was the part swim was missing :)

[FrenchFries]

sounds to swim like swiy is in a state of serious denial or rationalization about the repercussions of ingesting Isopropyl Alcohol. Swiy could just save himself the trouble and go do some shots of nail polish remover. Any way though, the exact effect that this substance has on the human body at a cellular level and how it does it's damage is beyond swim's knowledge. Just take it at face value that isopropyl alcohol will damage your liver and kidneys on it's first pass through the metabolism and then after going through the liver the acetone it's metabolized to gets to go to work on your body. Tell you what, go stick your hand in a bucket full of rubbing alcohol mixed with nail polish remover, then pull your hand out and let it dry. Your skin is going to be all ashy, dry and cracked well that's what drinking isopropyl is basically doing to you internally.
For lack of a clear scientific explanation why not to drink that shit, let's use common sense, and look at it this way. THEY DO NOT SERVE IT IN BARS! It is not an ingredient in any alcoholic drinks, period. How many people have you seen besides winos that sit down and crack open an ice cold bottle of rubbing alcohol, none. Some things are just poisonous to humans, now it would be great if we could just run around eating and drinking whatever we wanted to see what kind of head change it gives us, but after several thousand years of running around learning not to do that shit the hard way, we have evolved to the point of being able to label poisons as poison and food as food and so on. Any way, point is, someone took the time to study isopropyl alcohols effects on the human organism, which are not good regardless of rationalizations and so we don't consume it. Now if swiy is trying to find out why it's toxic for the purposes of pure knowledge, you could probably ask a doctor or even call the poison control center and find out exactly how it kills you.

[Paracelsus]

In case you didn't notice, the purpose of this thread was discussion of scientific information about the mechanisms of isopropanol toxicity. There's no need for scaremongering and exaggerations.

Don't hijack this thread, it's against the rules.

[FrenchFries]

oh sorry, thought SWIY was just looking for reason not to drink iPrOH.

[FrenchFries]

okay, according the american emergency medicine journal, they believe that isopropyl alcohol is poisonous because of acidosis without ketosis

[FrenchFries]

Background

Alcoholic ketoacidosis (AKA) is an acute metabolic acidosis that typically occurs in people who chronically abuse alcohol and have a recent history of binge drinking, little or no food intake, and persistent vomiting. AKA is characterized by elevated serum ketone levels and a high anion gap. A concomitant metabolic alkalosis is common, secondary to vomiting and volume depletion. Although AKA most commonly occurs in adults with alcoholism, AKA has been reported in less-experienced drinkers of all ages.
Pathophysiology


AKA is a result of starvation with glycogen depletion and counter-regulatory hormone production, a raised nicotinamide adenine dinucleotide (NADH) to nicotinamide adenine dinucleotide (NAD+) ratio related to the metabolism of ethanol, and volume depletion, resulting in ketogenesis.

When the dietary intake of carbohydrates is insufficient to supply glucose for the body's needs and hepatic glycogen stores are depleted by fasting, ketones are produced in the liver as an alternative source of energy. Two steps are required for ketogenesis: (1) enhanced lipolysis with an increased delivery of free fatty acids to the liver and (2) an alteration in hepatic metabolism by which these free fatty acids are converted preferentially into ketones instead of into triglycerides. Decreased insulin activity, increased counter-regulatory hormone levels (primarily glucagon, but also cortisol, catecholamines, and growth hormone), and volume depletion all play a role in ketogenesis. The body's response to starvation is a decrease in insulin activity and an increase in the production of counter-regulatory hormones. These counter-regulatory hormones cause the release of free fatty acids from peripheral adipose tissue. However, excess fatty acids alone are insufficient to cause ketoacidosis since, normally, the liver metabolizes free fatty acids into triglycerides. The key difference in the starvation state is in mitochondrial enzyme activity; specifically, the rate at which carnitine acyltransferase (CAT) transports free fatty acids into the mitochondria for oxidation. CAT activity is low in the fed state and accelerated in the fasting state. Glucagon excess is believed to have the major role in this hepatic response.
Prolonged vomiting leads to dehydration, which decreases renal perfusion, thereby limiting urinary excretion of ketoacids. Moreover, volume depletion increases the concentration of counter-regulatory hormones, further stimulating lipolysis and ketogenesis.


Ethanol is oxidized to acetaldehyde, which is itself oxidized to acetate. Both steps require the reduction of nicotinamide adenine dinucleotide (NAD+) to reduced nicotinamide adenine dinucleotide (NADH). The increased ratio of NADH to NAD+ has several implications: (1) impaired conversion of lactate to pyruvate with an increase in serum lactic acid levels, (2) impaired gluconeogenesis because pyruvate is not available as a substrate for glucose production, and (3) a shift in the beta-hydroxybutyrate (β-OH) to acetyl acetate (AcAc) equilibrium toward β-OH. β-OH is the predominate ketone in AKA. Understanding this is essential because routine clinical assays for ketonemia test for AcAc and acetone but not for β-OH. Clinicians underestimate the degree of ketonemia if they rely solely on the results of laboratory testing.