Pill Pushing©

The Best of Pill Pushing - Amyl nitrate - From angina pectoris to Donna Summer - (6/21/2018)

By Dr. Ron Gasbarro

The drug in question: Amyl nitrate.

Our culture at that time: By the 1840s, America was still taking shape. During that decade, Iowa, Wisconsin, Texas, and Florida were admitted to the Union, while Minnesota became a United States territory. There were 5 presidents during that decade with two – Zachary Taylor and William Henry Harrison – dying while in office. US postage stamps were issued for the first time: a 5 cent and a 10 cent stamp, is equal to $1.35 and $2.65 today, respectively. The California Gold Rush was on. In 1843, an alligator fell from the sky during a thunderstorm in Charleston, South Carolina. And in 1847, amyl nitrate was discovered as a treatment for angina pectoris – or chest pains. Until the discovery of amyl nitrate, physicians had treated the chest pains by using leeches to "bleed" the body of impurities [Corral-Rodriguez, 2010]. Amyl nitrate was more successful in treating chest pains because it dilated blood vessels, allowing the heart to receive more oxygen and thereby relieving the pain.

The good, the bad, and/or the ugly: For decades, amyl nitrate came in small glass vials that one broke under one’s nose to inhale the drug. Vials of amyl nitrate became known as "poppers" because of the sound they made when crushed. The drug triggers an almost immediate jump in the heart rate and a corresponding drop in blood pressure, causing smooth muscle tissue to relax. At the same time, it cuts the amount of oxygen to the brain, causing a sudden, intense weakness and dizziness that lasts several minutes. 

Among these side effects was a short but dizzying burst of euphoria. Thus, as even more effective ways to control chest pains were marketed – such as nitroglycerin transdermal patches, sublingual tablets, and a mouth spray – the drug gained a status that far outweighed its original intended use – that of a recreational drug [Parker, 1998]. 

The downside of fun: Recreational use of amyl nitrate involves inhaling this substance for short-term intoxication effects, a practice known as huffing. Inhaling amyl nitrate causes brief intoxication. Effects as listed by the American Council on Drug Education (ACDE) can include excitability, giddiness, lowering of inhibitions and heightened sensual awareness. The effects typically last less than a minute, leading the individual to keep taking more hits. An individual who has been inhaling amyl nitrate can develop outward signs as well, according to the ACDE. He might have slurred speech, lack of coordination, an unsteady gait, inflamed nose, nosebleeds, sores or a rash around the nose and mouth, and red, glassy, watery eyes.

Prolonged huffing of amyl nitrate can cause more serious symptoms. The individual may experience dizziness, fatigue, a pounding headache, nausea, and vomiting, and might even fall into a coma. Memory problems, confusion, difficulty concentrating, disorientation, fright, panic, delirium, and hallucinations can occur. These psychological reactions can lead to risky or violent behavior.

Continued use of amyl nitrate can lead to permanent damage to the brain, bones, heart, kidneys, and liver, as explained by the US Army Center for Health Promotion and Preventive Medicine. It may cause permanent hearing loss, as well as chronic tremors and slurred speech. Continued use can also result in chronic memory loss, emotional instability, mental disturbance, and ongoing hallucinations. It is flammable so do not take a snort with a cigarette hanging from your mouth. 

The impact of the drug on our culture:
 In 1960, the US Food and Drug Administration declared that amyl nitrate did not need a prescription and that it could be sold over-the-counter [Newell, 1985]. Over time, amyl nitrate was used less clinically but more recreationally as it grew in popularity following rumors that it intensified sexual orgasm. Although no research exists to suggest that amyl nitrate is an effective aphrodisiac, by the 1950s and 1960s, it had gained a reputation as a party drug among gay urbanites in both Britain and the United States [Sigell, 1978; McManus, 1982].

During the 1960s, amyl nitrate, along with a variety of other drugs, including marijuana, heroin, opium, LSD, and amphetamines, made its way to US soldiers fighting in Vietnam [Corral-Rodriguez, encyclopedia.com; 2015]. When the soldiers returned to the US after their tour of duty, many continued their popper habit. The FDA reinstated its ban on amyl nitrate without a prescription in 1969, following reports from American soldiers and veterans of serious problems caused by the drug. These problems included skin burns, fainting, dizziness, breathing difficulties, and blood abnormalities.

The FDA make a decision in the early 1960’s not to require a prescription to purchase the inhalant. When the FDA reinstated the prescription requirement in 1969, clandestine laboratories got around it by using slightly altered formulas, such as butyl nitrate, which produced the same basic effect [Haverkos, 1988]. Throughout the 1970s, the drug became popular among young gay males for use in discos and dance clubs to get a momentary "rush" while dancing. Donna Summers’ 6-minute version of “I Feel Love” used up a lot of poppers and the song was the perfect anthem for the inhaled drug.

Amyl = AIDS? For a while, inhaled nitrates were implicated in the as one of the causes of acquired immunodeficiency disease (AIDS) [Romanelli, 2004]. When AIDS cases were first recognized in 1981, nitrates were proposed as a possible cause of the new syndrome [Durack, 1981; CDC, 1982]. Nitrate abuse was virtually universal among the gay men diagnosed with AIDS in 1980-1983. However, these theories fizzled when the disease was recognized among intravenous drug users, hemophiliacs, and other heterosexual men and women who did not consistently report using nitrates. In 1983, human immunodeficiency virus (HIV) was discovered and reported as the cause of AIDS [Barre-Sonoussi, 1983; Popovic, 1984]. Subsequently, other hypotheses suggesting nitrates as promoting factors in AIDS have been proposed. Most notably and most logical were reports that nitrates may enhance HIV transmission by their association with risky sexual behaviors and HIV infection among gay men. Other theories, pretty much debunked or not fully studied included the use of amyl nitrate and its association with immune suppression, thus accelerating the onset of symptomatic disease, and its association with the development of AIDS-related Kaposi's sarcoma.

Where the drug is today: The possible links of nitrates to AIDS and the other known adverse effects of these inhaled substances suggest that more attention to these products by clinicians and researchers is warranted. The use of nitrate inhalants should be discouraged. Researchers should continue to study the associations between nitrate use and HIV/AIDS. Encouraging the decline in nitrate abuse appears to be a worthwhile public health goal. However, the most effective ways to accomplish this goal has not been elucidated. In the United States, laws banning nitrate manufacture and sale were enacted in 1988 and 1990 [Haverkos, 1988]. Nevertheless, nitrate inhalants continue to be sold today in adult bookstores or head shops – sometimes called VCR cleaners or room deodorizers [Newell, 1985; Berlin, 1987]. They can also be purchased online from distributors in Eastern Europe and other areas. 

While amyl nitrate is difficult to find, its chemical cousin, butyl nitrate can be found in porn or head shops. Like amyl nitrate, butyl nitrite is a vasodilating drug that relaxes smooth muscle tissue and increases the diameter of blood vessels. The drug lowers blood pressure to dangerous levels. Butyl nitrite can thin the walls of blood vessels in the brain, which may lead to strokes. This drug has a unique smell, like dirty sweaty socks, which is reflected in one of its names, "locker room." Another name for butyl nitrite is "rush," which relates to the rush of blood out of the brain and the resulting intoxication. Butyl nitrate has no clinical value and should be considered hazardous to one’s health.

Ron Gasbarro, PharmD is a registered pharmacist, medical writer, and principal at Rx-Press.com. Read more at www.rx-press.com. 


References 

Abrams, J. Hemodynamic effects of nitroglycerin and long-acting nitrates. Am Heart J 1985; 110:216.

Barre-Sinoussi F, Chermann JC, Rey F, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983;220:868-871.

Berlin R. Historical aspects of nitrate therapy. Drugs 1987;33:1–4.

Centers for Disease Control. Epidemiologic aspects of the current outbreak of Kaposi's sarcoma and opportunistic infections. N Engl J Med. 1982;306:248-252.

Corral-Rodríguez MA, Macedo-Ribeiro S, Pereira PJ, Fuentes-Prior P. Leech-derived thrombin inhibitors: From structures to mechanisms to clinical applications. J Med Chem.2010;53:3847–61. 

Durack DT. Opportunistic infections and Kaposi's sarcoma in homosexual men. N Engl J Med. 1981; 305:1465-1467.

Haverkos HW, Dougherty JA, eds. Health hazards of nitrate inhalants. NIDA research monograph 83. Washington DC: U.S. Government Printing Office, 1988. 

McManus TJ, Starrett LA, Harris JRW. Amyl nitrate use by homosexuals [letter]. Lancet 1982;1:503.

Newell GR, Mansell PW, Spitz MR, et al. Volatile nitrates: use and adverse effects related to the current epidemic of the acquired immunodeficiency syndrome. Am J Med 1985;78:811–16.

Parker, JD, Parker, JO. Nitrate therapy for stable angina pectoris. N Engl J Med 1998; 338:520-531.

Popovic M, Sarngadharan MG, Read E, Gallo RC. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984;224:497-500. 

Romanelli F, Smith KM, Thornton AC, Pomeroy C. Poppers: epidemiology and clinical management of inhaled nitrate abuse. Pharmacotherapy. 2004;24:69-78.

Sigell LT, Kapp FT, Fusaro GA, et al. Popping and snorting volatile nitrates: a current fad for getting high. Am J Psychiatry. 1978;135:1216–18.



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