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Pharmacology

  • The Tragedy That Transformed Medicine: The Legacy of the Tylenol Murders

    The Tragedy That Transformed Medicine: The Legacy of the Tylenol Murders

    Discovery of Tylenol

    Acetaminophen—known as paracetamol in the Old World—was rediscovered not once, but three times.

    First by French scientist Gerhard in 1852, who hasn’t found it useful.

    Acetoaminophen got a second chance in 1873 in a laboratory of an American chemist, Harmon Northrop Morse, now considered the father of acetaminophen.

    Harmon Northrop Morse is considered a “father of acetaminophen”

    This time paracetamol has been tested as a potential safer alternative to its cousin acetanilid, which caused methemoglobinemia, a condition of a reduced capacity of a red blood cell to bind and transfer oxygen. Tests on humans showed a mild to moderate tendency to cause methemoglobinemia and acetaminophen was shelved for almost eight decades.

    Acetaminophen finally found its way to the market

    In 1953, acetaminophen was finally entered the market as a safer alternative to aspirin for kids and adults with GI ulcers. Thankfully, to the Food, Drug, and Cosmetic Act, a pharma should provide both efficacy and safety to the FDA before medications enter the market.

    Two companies at the same decided to market acetoamiphen:

    • Tylenol – by McNeil
    • Panadol – by Heleon plc

    Chicago murders and Tylenol

    For almost three decades, McNeil and its parent company Johnson and Johnson (J&J) have enjoyed a steady growth of market share of their paracetamol brand.

    The success story took a sudden turn in 1982 when Tylenol was undisputed leader of the consumer market with 35% of sales of acetaminophen in the US. Nothing is too big to fail, specifically when it comes to patient safety.

    In 1982, multiple people in Chicago lost their lives after consuming Tylenol Extra laced with cyanide. “An infamous painkiller delivered a painful demise to unsuspecting victims,” read the shocking headlines, sparking unprecedented fear among consumers. As panic spread, Tylenol’s market share plummeted to just 8%.

    J&J reacted immediately by recalling over 30 million bottles of Tylenol. An R&D department of a pharmaceutical giant came up with a quick solution – a nice rounded seal on top of the, which became de facto an industry standard for anti-tampering.

    With a fast and transparent approach to the problem, the manufacturer was able to win public trust again and everything lost was soon regained. Now J&J recall is a successful case study for many MBA courses around the globe.

    Fortunately, J&J hasn’t settled with alterations to the packaging and soon came up with an alternative excipient formula for Tylenol giving a pill recemblence to jelly pop candy. Those candies are incredibly difficult to tamper with, making it nearly impossible to insert or introduce any foreign substances..

    Food and Drug Act 1983

    In 1983, the Food and Drug Act classified tampering as a federal offense, significantly increasing the penalties for offenders. One such opportunist from NYC attempted to blackmail J&J, demanding $1 million in ransom to halt the cyanide poisonings. However, the court sentenced him to 20 years in prison for extortion—a daring scheme met with dire consequences.

  • Diethylene Glycol: The Deadly Molecule That Changed Medicine Forever

    Diethylene Glycol: The Deadly Molecule That Changed Medicine Forever

    You can’t expect more from this small molecule of Diethylene glycol (DEG). Having a humbling origins of an ether of an antifreeze (CH2OH)2 , the DEG is one of the dozens interim substances in the process of manufacturing of polyester raisins.

    DEG
    Diethylene glycol

    If only not a single blunder and a corporate greed that put it in the spotlight of as “Elixir Sulfanilamide”, DEG would be one million other molecules used in organic polymer synthesis.

    Elixir Sulfanilamide

    A year 1938, sulfa drugs, that miraculously cured a bad pneumonia of Winston Churchill in few days are now available for everyone who can swallow a pill. Prominent scientists of this era are struggling with a challenge of getting a potion for those who still cannot gulp a whole tablet.

    One of those griddling with the task is Harold Cole Watkins. Working as a chief chemist at Messengil, he decided to use Diethylene glycol as a dissolvent, which on paper and in vitro was a brilliant idea.

    Flavored with a raspberry it was ready to hit the market as “Sulfanilamide elixir”, which by mid 1938 started selling countrywide – an extreme case for a new drug today, it was absolute reality of that time – you don’t need to prove neither efficacy no safety of the remedies you producing. By the Food and Drug Act of 1906 your medication needs to be “original”, period.

    Diethylene Glycol. Remedy for disaster

    It was of the most tragic launches in history. One third, more than 100 kids died of renal failure, caused by the dissolvent writher than antibacterials itself.

    Once consumed, DEG quickly enters the bloodstream and turns to liver. Having not one but two OH groups it provides an excellent substrate for liver to practice oxydation – the process of adding more oxygen. The result is 2-hydroxyethoxyacetic acid or HEAA, which accountable for the kidney and nervous system toxicity of Diethylene Glycol poisoning.

    The reaction from public and lawmakers was almost immediate – in late 1938 Federal Food, Drug, and Cosmetic Act was born and enacted by Franklin D. Roosevelt.

    US became first among developed nations to enact drug approval regulations, that helped the country to avoid infamous thalidomide tragedy.

  • Top 7 common remedies from lies

    Imagine you developed elixir of truth to eradicate all lies on the planet, putting an end of politicians deceiving voters with misinformation campaigns and stopping greedy marketing guru from pitching “yet another get rich quick scheme”.

    What a wonderful world it would be if everyone took a sip of your miracle “truth serum,” right? Wrong. Instead of utopia, it would likely set the world ablaze—throwing stock markets into turmoil, shattering international relations, crushing business alliances, and upending millions of families overnight.

    As one of my favorite movie doctor kept saying: “Everybody lies”. Luckily for our civilization, most people lie to each other for a reason. Some of those reasons might be even noble – to avoid giving in secretes to the adversary. We call it “patriotism”—the unwavering resolve of an individual to stay silent, no matter the circumstances, when faced with those they consider enemies.

    Secret services around the history of human kind have been trying to find a way to get the truth from the adversaries. And throughout history, secret services have relentlessly sought ways to extract the truth from their adversaries. Torture was likely one of the earliest methods used to force confessions. In Orwell’s iconic 1984, Winston is mercilessly broken by the regime until every ounce of rebellion within him is crushed.

    In this article we will explore what one might consider a more humane way of extracting secret information from the captives. Truth serums are chemical substances designed to impair a person’s ability to exercise judgment and conceal information, making them more susceptible to revealing hidden truths.

    Although some of them were used or tested by “serious” secret services, no drug has been proven to reliably force truthfulness, and information obtained under their influence is often unreliable.

    Common “Truth Serum” Substances

    Alcohol

    Historically, alcohol was the first “elixir of trust” (although an elixir is often something dissolved in ethanol, which helped to loosen the tongues of several dozen courtiers, likely preventing multiple acts of treason.

    “A drunk mind speaks a sober heart”. Alcohol is a central nervous system depressant that impairs higher brain functions, particularly in the neocortex, which governs reasoning, impulse control, and social awareness.

    As these regulatory centers weaken, individuals may speak more freely, sometimes revealing personal thoughts or confidential information without considering the consequences. However, this also means that their statements may be exaggerated, distorted, or completely unreliable.

    Sodium Pentothal (Thiopental Sodium)

    • A barbiturate that induces a sedative state, sometimes lowering inhibitions.
    • Used by intelligence agencies and police in historical interrogations.
    • Often portrayed in movies as a classic truth serum.

    Sodium Amytal (Amobarbital)

    • Another barbiturate with effects similar to Sodium Pentothal.
    • Used in psychiatric applications to help patients recall repressed memories.
    • Some law enforcement and intelligence agencies experimented with it.

    Scopolamine

    • A powerful anticholinergic drug derived from plants like deadly nightshade.
    • Used in early 20th-century interrogations but caused confusion and hallucinations.
    • Known as “Devil’s Breath” when used as a criminal drug to induce suggestibility.

    Midazolam

    • A benzodiazepine with amnesic and sedative properties.
    • Used in some controversial interrogations.
    • More likely to cause compliance rather than truthfulness.

    Chloral Hydrate

    • A sedative-hypnotic drug historically used for sleep induction.
    • Has depressant effects but is not reliable as a truth serum.

    LSD (Lysergic Acid Diethylamide)

    The CIA experimented with LSD under Project MKUltra to determine if it could be used as a mind-control or truth serum agent.Instead of truthfulness, it caused hallucinations and paranoia.

      Effectiveness and Ethical Concerns

      None of these drugs reliably force truthfulness; they mostly lower inhibitions, making people more talkative or suggestible.

      Many governments have banned or abandoned their use due to ethical and legal concerns.

      Information obtained under these substances is often inaccurate or mixed with false memories.

    1. How does scopolamine patch work

      Scopolamine mechanism of action in a nutshell:

      Scopolamine inhibits signals originating from the vestibular system before they reach the vomiting center by blocking activity of muscarinic receptors.

      In motion sickness, a sensory mismatch occurs due to a disconnect between visual, vestibular (balance), and proprioceptive (muscle) inputs received by the brain. This discrepancy is interpreted as a potential toxic exposure, triggering the body’s defense mechanisms, including activation of the vomiting center.

      Scopolamine mechanism of action

      From Mandrake to Motion Patch A Brief History of Scopolamine

      When I came across advertisement of a motion sickness patch, claiming it is “100% natural, herbal based”, I always remind myself that most of our today’s effective pharmaceuticals had herbal ancestors. Scopolamine, which is now commonly used for seasickness and became the first ever medication with transdermal application (aka dermal patch) is excellent example of it.

      Scopolamine, M-acetilcholine blocker also know as hyoscine is common remedy for motion sickness first isolated in 1880 from Scopolia carniolica by German chemist Albert Ladenburg. Like its pharmacological buddy atropine, scopolamine is abundantly found in mandrake—a legendary “screaming plant” said to drive anyone who hears its cries to madness.

      Before being approved by FDA in 1979 for the prevention of nausea and vomiting associated with motion sickness and surgical procedures, scopolamine was known for decades as poison and “truth serum” drug. In the WWII movie “The guns of Navarone” the German general demands that scopolamine be used to interrogate the prisoner left behind by the group.

      Criminals have exploited his ability to induce “anesthetic amnesia” for more nefarious purposes, using it to facilitate robbery or sexual assault. The toxicity and potential side effects are far benign when scopolamine used in therapeutic doses of a transdermal patch and usually limited to:

      • Blurred vision (due to pupil dilation)
      • Increased intraocular pressure (risk in glaucoma)
      • Tachycardia (increased heart rate)
      • Dry mouth (xerostomia)
      • Constipation (due to reduced gut motility)
      • Urinary retention
      • Difficulty urinating (especially in benign prostatic hyperplasia)
      • Decreased sweating (anhidrosis)
      • Risk of hyperthermia (especially in hot environments)

      How scopolamine helps in motion sickness

      Scopolamine blocks signals from the vestibular system before they are transmitted to the vomiting center.

      Motion sickness pathophysiology

      Motion sickness arises due to sensory conflict, where signals from the eyes, inner ear (vestibular system), and somatosensory system do not align. The brain is getting suspicious “there is something wrong with them”, interpreting the disarray of stimuli as neurotoxin poisoning with the sequential reaction “Hey, empty the stomach, we are getting poisoned!”

      The chain of command goes as follows:

      1. Balance organ (semicircular channels of an inner ear) and cerebellum start bombarding vestibular nuclei
      2. Overstimulation of the vestibular nuclei results in activation of the chemoreceptor trigger zone (CTZ) and vomiting center in the medulla.
      3. Vomiting center sends a signal “to empty the stomach”

      While the whole interplay is described in the separate article, as well as pharmaceutical management of a motion sickness, scopolamine only targets a step in preventing the transmission of a signal from vestibular nuclei to vomiting centers and CTZ.