Alcohols (medicine)

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Alcohol
Ethanol-2D-skeletal.svg
Ethanol is a commonly used medical alcohol.
Clinical data
Routes of
administration 		Topical, intravenous, by mouth
Drug class Antiseptics, disinfectants, antidotes
ATC code
Legal status
Legal status
Pharmacokinetic data
Metabolism Liver
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII

Alcohols, in various forms, are used medically as an antiseptic, disinfectant, and antidote. [1] Alcohols applied to the skin are used to disinfect skin before a needle stick and before surgery. [2] They may also be used as a hand sanitizer; [2] to clean other areas; [2] and in mouthwashes. [3] [4] [5] Taken by mouth or injected into a vein, ethanol is used to treat methanol or ethylene glycol toxicity when fomepizole is not available. [1]

Contents

Side effects of alcohols applied to the skin include skin irritation. [2] Care should be taken with electrocautery, as ethanol is flammable. [1] Types of alcohol used include ethanol, denatured ethanol, 1-propanol, and isopropyl alcohol. [6] [7] Alcohols are effective against a range of microorganisms, though they do not inactivate spores. [7] Concentrations of 60% to 90% work best. [7]

Uses

95% ABV ethanol is known as spiritus fortis in medical context.

Alcohol septal ablation

Ablysinol (a brand of 99% ethanol medical alcohol) was sold from $1,300 to $10,000 per 10-pack[ Give volume amount please ] in 2020 due to FDA administrator action granting exclusivity when used for treating hypertrophic obstructive cardiomyopathy with alcohol septal ablation in the US through 2025, despite "misuse" of the orphan drug act. [8] [9] [10] [ unreliable source? ]

Antiseptics

Alcohols

Ethanol is listed under Antiseptics, and Alcohol based hand rub under Disinfectants, on the World Health Organization's List of Essential Medicines. [6]

Applied to the skin, alcohols are used to disinfect skin before a needle stick and before surgery. [2] They may be used both to disinfect the skin of the person and the hands of the healthcare providers. [2] They can also be used to clean other areas, [2] and in mouthwashes. [3]

Both ethanol and isopropyl alcohol are common ingredients in topical antiseptics, including hand sanitizer. [11]

Risks

Research indicates that alcohol used as pre-surgical antiseptic preparations for ear procedures may have some ototoxic properties. [12] In this regard, these alcohol preparations may be considered potential ototoxic medication.

Antidote

When taken by mouth or injected into a vein ethanol is used to treat methanol or ethylene glycol toxicity [13] when fomepizole is not available. [1]

Mechanism

Ethanol, when used for toxicity, competes with other alcohols for the alcohol dehydrogenase enzyme, lessening metabolism into toxic aldehyde and carboxylic acid derivatives, and reducing more serious toxic effect of the glycols to crystallize in the kidneys. [14]

Euthanasia

Alcohol can intensify the sedation caused by hypnotics/sedatives such as barbiturates, benzodiazepines, sedative antihistamines, opioids, nonbenzodiazepines/Z-drugs (such as zolpidem and zopiclone). [15]

In the Netherlands, pentobarbital is part of the standard protocol for physician-assisted suicide for self-administration by the patient. [16] It is given in liquid form, in a solution of sugar syrup and alcohol, containing 9 grams of pentobarbital. This is preceded by an antiemetic to prevent vomiting. [16]

Medicinal solvent

Ethanol, often in high concentrations, is used to dissolve many water-insoluble medications and related compounds. Liquid preparations of pain medications, cough and cold medicines, and mouth washes, for example, may contain up to 25% ethanol [17] and may need to be avoided in individuals with adverse reactions to ethanol such as alcohol-induced respiratory reactions. [18] Ethanol is present mainly as an antimicrobial preservative in over 700 liquid preparations of medicine including acetaminophen, iron supplements, ranitidine, furosemide, mannitol, phenobarbital, trimethoprim/sulfamethoxazole and over-the-counter cough medicine. [19]

Some medicinal solutions of ethanol are also known as tinctures.

Mouthwash

Usually mouthwashes are antiseptic solutions intended to reduce the microbial load in the mouth, although other mouthwashes might be given for other reasons such as for their analgesic, anti-inflammatory or anti-fungal action. Also, alcohol is added to mouthwash not to destroy bacteria but to act as a carrier agent for essential active ingredients such as menthol, eucalyptol and thymol, which help to penetrate plaque. [20]

A 2020 systematic review and meta-analysis concluded that there is no definitive link between alcohol-based mouthwash use and the risk of oral cancer. [21] This should not be confused with the fact that alcohol consumption at any quantity is a risk factor for alcohol and cancer such as cancers of the mouth, esophagus, pharynx and larynx. [22]

Sclerosant

Absolute ethanol is used as a sclerosant in sclerotherapy. Sclerotherapy has been used "in the treatment of simple pleural effusions, vascular malformations, lymphocytes and seromas." [23]

Sedative

Ethchlorvynol, developed in the 1950s, was used to treat insomnia, but prescriptions for the drug had fallen significantly by 1990, as other hypnotics that were considered safer (i.e., less dangerous in overdose) became much more common. Also, ethchlorvynol is not compatible with intravenous injection like ethanol—serious injury (including the loss of limbs due to vascular injury) or death can occur when it is used in this manner. [24] It is no longer prescribed in the United States due to unavailability, but it is still available in some countries and would still be considered legal to possess and use with a valid prescription.

Society and culture

Unproven methods against COVID-19

Unproven COVID-19 prevention from alcohol consumption

Drinking alcohol will not prevent or cure COVID-19, [25] contrary to some claims. [26]

Unproven COVID-19 hand sanitizer

Vodka was alleged to be an effective homemade hand sanitizer, or an ingredient in one. The company whose brand was alleged to be protective responded to the rumours by citing the US Centers for Disease Control and Prevention statement that hand sanitizers needed to be at least 60% alcohol to be effective, and stating that their product was only 40% alcohol. [27] [28] [ medical citation needed ]

History

Ancient world

Since antiquity, prior to the development of modern agents, alcohol was used as a general anesthetic. [29]

Detail from The Good Samaritan by Cornelis van Haarlem (1627) showing the Samaritan pouring oil and wine on the injured man's wounds Parable of the Good Samaritan (detail) by Cornelis van Haarlem.jpg
Detail from The Good Samaritan by Cornelis van Haarlem (1627) showing the Samaritan pouring oil and wine on the injured man's wounds

In the history of wound care, beer, [30] and wine, [31] are recognized as substances used for healing wounds.

Late Middle Ages

Alcohol has been used as an antiseptic as early as 1363, with evidence to support its use becoming available in the late 1800s. [32]

At times and places of poor public sanitation (such as medieval Europe), the consumption of alcoholic drinks was a way of avoiding water-borne diseases such as cholera. [33]

Modern period

Early doctors recognized that ethanol was a risky anesthetic because it could lead to death from alcohol poisoning or vomit inhalation (pulmonary aspiration). This led to use of alternatives in antiquity, such as opium and cannabis, and later diethyl ether starting in the 1840s. [34] As safer options became available, ethanol was eventually phased out as a general anesthetic.

Methylpentynol, discovered 1913, prescribed for the treatment of insomnia, but its use was quickly phased out in response to newer drugs with far more favorable safety profiles. [35] [36] [37] The drug has been replaced by benzodiazepines and is no longer sold anywhere. [38]

Related Research Articles

<span class="mw-page-title-main">Ethanol</span> Organic compound (CH₃CH₂OH)

Ethanol is an organic compound with the chemical formula CH3CH2OH. It is an alcohol, with its formula also written as C2H5OH, C2H6O or EtOH, where Et stands for ethyl. Ethanol is a volatile, flammable, colorless liquid with a characteristic wine-like odor and pungent taste. In nature, grape-sugar breaks up by the action of fermentation into alcohol or carbonic acid, without anything being added. As a psychoactive depressant, it is the active ingredient in alcoholic beverages, and the second most consumed drug globally behind caffeine.

<span class="mw-page-title-main">Ethchlorvynol</span> Group of stereoisomers

Ethchlorvynol is a GABA-ergic hypnotic sedative medication first developed by Pfizer in the 1950s. In the United States it was sold by Abbott Laboratories under the trade name Placidyl. Placidyl was available in 200 mg, 500 mg, and 750 mg strength gel filled capsules. While the 500 mg and 750 mg strength capsules were for use in reducing sleep latency, the 200 mg strength capsules were intended to be used to re-induce sleep in case of early awakening. Abbott discontinued production in 1999, due to it being replaced by the benzodiazepine family and its widespread abuse, after which Placidyl was available for about a year in the United States. Although, theoretically, ethchlorvynol could be manufactured for sale in the United States by another pharmaceutical company, no pharmaceutical company has chosen to do so. Individuals with a valid prescription for the substance may legally transport a reasonable amount of ethclorvynol with them into the United States.

<span class="mw-page-title-main">Tincture of iodine</span> Antiseptic solution rubbed on skin before surgical operations

Tincture of iodine, iodine tincture, or weak iodine solution is an antiseptic. It is usually 2 to 3% elemental iodine, along with potassium iodide or sodium iodide, dissolved in a mixture of ethanol and water. Tincture solutions are characterized by the presence of alcohol. It was used from 1908 in pre-operative skin preparation by Italian surgeon Antonio Grossich.

<span class="mw-page-title-main">Disinfectant</span> Antimicrobial agent that inactivates or destroys microbes

A disinfectant is a chemical substance or compound used to inactivate or destroy microorganisms on inert surfaces. Disinfection does not necessarily kill all microorganisms, especially resistant bacterial spores; it is less effective than sterilization, which is an extreme physical or chemical process that kills all types of life. Disinfectants are generally distinguished from other antimicrobial agents such as antibiotics, which destroy microorganisms within the body, and antiseptics, which destroy microorganisms on living tissue. Disinfectants are also different from biocides—the latter are intended to destroy all forms of life, not just microorganisms. Disinfectants work by destroying the cell wall of microbes or interfering with their metabolism. It is also a form of decontamination, and can be defined as the process whereby physical or chemical methods are used to reduce the amount of pathogenic microorganisms on a surface.

<span class="mw-page-title-main">Benzalkonium chloride</span> Surfactant and antiseptic agent

Benzalkonium chloride, also known as alkyldimethylbenzylammonium chloride (ADBAC) and by the trade name Zephiran, is a type of cationic surfactant. It is an organic salt classified as a quaternary ammonium compound. ADBACs have three main categories of use: as a biocide, a cationic surfactant, and a phase transfer agent. ADBACs are a mixture of alkylbenzyldimethylammonium chlorides, in which the alkyl group has various even-numbered alkyl chain lengths.

<span class="mw-page-title-main">Chlorhexidine</span> Disinfectant and antiseptic

Chlorhexidine is a disinfectant and antiseptic with the molecular formula C22H30Cl2N10, which is used for skin disinfection before surgery and to disinfect surgical instruments. It is also used for cleaning wounds, preventing dental plaque, treating yeast infections of the mouth, and to keep urinary catheters from blocking. It is used as a liquid or a powder. It is commonly used in salt form, either the gluconate or the acetate.

An antimicrobial is an agent that kills microorganisms (microbicide) or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals are used against fungi. They can also be classified according to their function. Antimicrobial medicines to treat infection are known as ⠀⠀antimicrobial chemotherapy, while antimicrobial drugs are used to prevent infection, which known as antimicrobial prophylaxis.

<span class="mw-page-title-main">Povidone-iodine</span> Antiseptic solution

Povidone-iodine (PVP-I), also known as iodopovidone, is an antiseptic used for skin disinfection before and after surgery. It may be used both to disinfect the hands of healthcare providers and the skin of the person they are caring for. It may also be used for minor wounds. It may be applied to the skin as a liquid, an ointment or a powder.

<span class="mw-page-title-main">Fomepizole</span> Medication

Fomepizole, also known as 4-methylpyrazole, is a medication used to treat methanol and ethylene glycol poisoning. It may be used alone or together with hemodialysis. It is given by injection into a vein.

Chloroxylenol, also known as para-chloro-meta-xylenol (PCMX), is a chlorine substituted phenol with a white to off-white appearance and a phenolic odor.

<span class="mw-page-title-main">Hand sanitizer</span> Alternative to hand washing

Hand sanitizer is a liquid, gel, or foam used to kill viruses, bacteria, and other microorganisms on the hands. It can also come in the form of a cream, spray, or wipe. While hand washing with soap and water is generally preferred, hand sanitizer is a convenient alternative in settings where soap and water are unavailable. However, it is less effective against certain pathogens like norovirus and Clostridioides difficile and cannot physically remove harmful chemicals. Improper use, such as wiping off sanitizer before it dries, can also reduce its effectiveness, and some sanitizers with low alcohol concentrations are less effective. Additionally, frequent use of hand sanitizer may disrupt the skin's microbiome and cause dermatitis.

<span class="mw-page-title-main">Lysol</span> Cleaning products brand name

Lysol is a brand of American cleaning and disinfecting products distributed by Reckitt, which markets the similar Dettol or Sagrotan in other markets. The line includes liquid solutions for hard and soft surfaces, air treatment, and hand washing. The active ingredient in many Lysol products is benzalkonium chloride, but the active ingredient in the Lysol "Power and Free" line is hydrogen peroxide. Lysol has been used since its invention in the late 19th century as a household and industrial cleaning agent, and previously as a medical disinfectant.

<span class="mw-page-title-main">Methylpentynol</span> Chemical compound

Methylpentynol is a tertiary pentynol with hypnotic/sedative and anticonvulsant effects and an exceptionally low therapeutic index. It was discovered by Bayer in 1913 and was used shortly thereafter for the treatment of insomnia, but its use was quickly phased out in response to newer drugs with far more favorable safety profiles.

A virucide is any physical or chemical agent that deactivates or destroys viruses. The substances are not only virucidal but can be also bactericidal, fungicidal, sporicidal or tuberculocidal.

Surrogate alcohol is a term for any substance containing ethanol, or other alcohols, that is intentionally consumed by humans but is not meant for human consumption. Some definitions of the term also extend to illegally produced alcoholic beverages.

Ethylene glycol poisoning is poisoning caused by drinking ethylene glycol. Early symptoms include intoxication, vomiting and abdominal pain. Later symptoms may include a decreased level of consciousness, headache, and seizures. Long term outcomes may include kidney failure and brain damage. Toxicity and death may occur after drinking even in a small amount as ethylene glycol is more toxic than other diols.

Isopropyl alcohol is a colorless, flammable, organic compound with a pungent alcoholic odor.

<span class="mw-page-title-main">Jeffrey Brent</span> Medical toxicologist

Jeffrey A. Brent is a medical toxicologist who is a distinguished clinical professor of medicine and emergency medicine at the University of Colorado, School of Medicine. In addition, he is a professor at the Department of Environmental and Occupational Health at the Colorado School of Public Health. He is also the past president of the American Academy of Clinical Toxicology, was editor in chief of the journal Toxicological Reviews, and was a member of the board of directors of the American College of Medical Toxicology. Previously, most of Brent's research focused on the use of fomepizole as a treatment for both methanol and ethylene glycol poisoning, and he led a trial of this drug which resulted in the FDA approving it in December 1997. Currently, Brent serves as Director of the Toxicology Investigators Consortium, an NIH and FDA supported multi center research and surveillance group. Brent is also a senior editor of "Critical Care Toxicology: Diagnosis and Management of the Critically Poisoned Patient", originally published in 2005, and now in its second edition, which was published in 2017.

<span class="mw-page-title-main">Methanol toxicity</span> Medical condition

Methanol toxicity is poisoning from methanol, characteristically via ingestion. Symptoms may include an altered/decreased level of consciousness, poor or no coordination, vomiting, abdominal pain, and a specific smell on the breath. Decreased vision may start as early as twelve hours after exposure. Long-term outcomes may include blindness and kidney failure. Blindness may occur after drinking as little as 10 mL; death may occur after drinking quantities over 15 mL.

<span class="mw-page-title-main">Alcohol (drug)</span> Active ingredient in fermented drinks

Alcohol, sometimes referred to by the chemical name ethanol, is the second most consumed psychoactive drug globally behind caffeine. Alcohol is a central nervous system (CNS) depressant, decreasing electrical activity of neurons in the brain. The World Health Organization (WHO) classifies alcohol as a toxic, psychoactive, dependence-producing, and carcinogenic substance.

References

  1. 1 2 3 4 British National Formulary: BNF 69 (69th ed.). British Medical Association. 2015. pp. 42, 838. ISBN   9780857111562.
  2. 1 2 3 4 5 6 7 World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. p. 321. hdl:10665/44053. ISBN   9789241547659.
  3. 1 2 Limeback H (11 April 2012). Comprehensive Preventive Dentistry. John Wiley & Sons. pp. 138–. ISBN   978-1-118-28020-1. Archived from the original on 18 September 2017.
  4. ↑ Kuriakose MA (8 December 2016). Contemporary Oral Oncology: Biology, Epidemiology, Etiology, and Prevention. Springer. pp. 47–54. ISBN   978-3-319-14911-0. Archived from the original on 18 September 2017.
  5. ↑ Jameel RA, Khan SS, Kamaruddin MF, Abd Rahim ZH, Bakri MM, Abdul Razak FB (October 2014). "Is synthetic mouthwash the final choice to treat oral malodour?". Journal of the College of Physicians and Surgeons--Pakistan. 24 (10): 757–762. PMID   25327922.
  6. 1 2 World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl: 10665/371090 . WHO/MHP/HPS/EML/2023.02.
  7. 1 2 3 McDonnell G, Russell AD (January 1999). "Antiseptics and disinfectants: activity, action, and resistance". Clinical Microbiology Reviews. 12 (1): 147–179. doi:10.1128/cmr.12.1.147. PMC   88911 . PMID   9880479.
  8. ↑ Paavola A (12 February 2020). "Why price of dehydrated alcohol is going from $1,300 to $10K". www.beckershospitalreview.com.
  9. ↑ "Biotech executives, having pledged fair pricing, criticize drugmaker for steep hike". BioPharma Dive.
  10. ↑ "Statement on Belcher Pharmaceuticals". linkedin. Retrieved 19 October 2023.
  11. ↑ "Q&A for Consumers | Hand Sanitizers and COVID-19". Center for Drug Evaluation and Research (CDER). U.S. Food and Drug Administration. 12 May 2023.
  12. ↑ Singh S, Blakley B (March 2018). "Systematic review of ototoxic pre-surgical antiseptic preparations - what is the evidence?". Journal of Otolaryngology - Head & Neck Surgery = le Journal d'Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale. 47 (1): 18. doi: 10.1186/s40463-018-0265-z . PMC   5831715 . PMID   29490694.
  13. ↑ Mégarbane B (24 August 2010). "Treatment of patients with ethylene glycol or methanol poisoning: focus on fomepizole". Open Access Emergency Medicine. 2: 67–75. doi: 10.2147/OAEM.S5346 . PMC   4806829 . PMID   27147840.
  14. ↑ Barceloux DG, Bond GR, Krenzelok EP, Cooper H, Vale JA (2002). "American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning". Journal of Toxicology. Clinical Toxicology. 40 (4): 415–446. doi:10.1081/CLT-120006745. PMID   12216995. S2CID   26495651.
  15. ↑ Yost DA (2002). "Acute care for alcohol intoxication" (PDF). Postgraduate Medicine Online. 112 (6). Archived from the original (PDF) on 14 December 2010. Retrieved 29 September 2007.
  16. 1 2 Köhler W (23 November 2000). "Euthanica". Euthanesia Dossier (in Dutch). NRC Webpagina's.
  17. ↑ "Alcohol Content in Common Preparations" (PDF). Medical Society of the State of New York. Archived from the original (PDF) on 29 April 2021. Retrieved 8 October 2019.
  18. ↑ Adams KE, Rans TS (December 2013). "Adverse reactions to alcohol and alcoholic beverages". Annals of Allergy, Asthma & Immunology. 111 (6): 439–445. doi:10.1016/j.anai.2013.09.016. PMID   24267355.
  19. ↑ Zuccotti GV, Fabiano V (July 2011). "Safety issues with ethanol as an excipient in drugs intended for pediatric use". Expert Opinion on Drug Safety. 10 (4): 499–502. doi:10.1517/14740338.2011.565328. PMID   21417862. S2CID   41876817.
  20. ↑ Toedt J, Koza D, Van Cleef-Toedt K (2005), Chemical composition of everyday products (illustrated ed.), Greenwood Publishing Group, pp. 48–49, ISBN   9780313325793
  21. ↑ Aceves Argemí R, González Navarro B, Ochoa García-Seisdedos P, Estrugo Devesa A, López-López J (June 2020). "Mouthwash With Alcohol and Oral Carcinogenesis: Systematic Review and Meta-analysis". The Journal of Evidence-Based Dental Practice. 20 (2): 101407. doi:10.1016/j.jebdp.2020.101407. PMID   32473798.
  22. ↑ Gormley M, Creaney G, Schache A, Ingarfield K, Conway DI (November 2022). "Reviewing the epidemiology of head and neck cancer: definitions, trends and risk factors". British Dental Journal. 233 (9): 780–786. doi:10.1038/s41415-022-5166-x. PMC   9652141 . PMID   36369568.
  23. ↑ Episalla NC, Orra S, Black CK, Dekker PK, Kim KG, Cardella JT, et al. (August 2021). "Sclerotherapy as an alternative treatment for complex, refractory seromas". Journal of Surgical Case Reports. 2021 (8). Oxford University Press: rjab224. doi:10.1093/jscr/rjab224. PMC   8384448 . PMID   34447570.
  24. ↑ Glauser FL, Smith WR, Caldwell A, Hoshiko M, Dolan GS, Baer H, et al. (January 1976). "Ethchlorvynol (Placidyl)-induced pulmonary edema". Annals of Internal Medicine. 84 (1): 46–48. doi:10.7326/0003-4819-84-1-46. PMID   942681.
  25. ↑ "Myth busters". who.int. World Health Organization.
  26. ↑ Baumgarten A. "10 common myths busted about coronavirus in North Dakota". The Dickinson Press. Retrieved 14 April 2020.
  27. ↑ "Fact or Fiction: Tito's Vodka can be used in hand sanitizer?". KGTV. 10 March 2020. Retrieved 9 April 2020.
  28. ↑ "Coronavirus: Don't use vodka to sanitise hands". BBC News. 6 March 2020.
  29. ↑ Eger II EI, Saidman LJ, Westhorpe RN (14 September 2013). The Wondrous Story of Anesthesia. Springer Science & Business Media. pp. 4–. ISBN   978-1-4614-8441-7. Archived from the original on 18 September 2017.
  30. ↑ Shah JB (September 2011). "The history of wound care". The Journal of the American College of Certified Wound Specialists. 3 (3): 65–66. doi:10.1016/j.jcws.2012.04.002. PMC   3601883 . PMID   24525756.
  31. ↑ John Gill's Exposition of the Bible Classic Bible Commentaries
  32. ↑ Block SS (2001). Disinfection, Sterilization, and Preservation. Lippincott Williams & Wilkins. p. 14. ISBN   9780683307405. Archived from the original on 13 January 2017.
  33. ↑ Dunn R. "Strong Medicine: Drinking Wine and Beer Can Help Save You from Cholera, Montezuma s Revenge, E. Coli and Ulcers 1". Scientific American Blog Network. Retrieved 27 June 2021.
  34. ↑ Grattan, N. "Treatment of Uterine Haemorrhage". Provincial Medicine and Surgical Journal. Vol. 1, No. 6 (Nov. 7, 1840), p. 107.
  35. ↑ Hirsh HL, Orsinger WH (January 1952). "Methylparafynol--a new type hypnotic. Preliminary report on its therapeutic efficacy and toxicity". American Practitioner and Digest of Treatment. 3 (1): 23–26. PMID   14903452.
  36. ↑ Schaffarzick RW, Brown BJ (December 1952). "The anticonvulsant activity and toxicity of methylparafynol (dormison) and some other alcohols". Science. 116 (3024): 663–665. Bibcode:1952Sci...116..663S. doi:10.1126/science.116.3024.663. PMID   13028241.
  37. ↑ Herz A (March 1954). "[A new type of hypnotic; unsaturated tertiary carbinols; experimental studies on therapeutic use of 3-methyl-pentin-ol-3 (methylparafynol)]". Arzneimittel-Forschung. 4 (3): 198–199. PMID   13159700.
  38. ↑ Hines RD (2002). The Pursuit of Oblivion. p. 327.
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