11 Paracetamol by Amelie

Paracetamol as we know it is one of the most widely used medicines worldwide, but what really is it? How does it work? And is it as safe as we all assume?

Acetaminophen is another name for Paracetamol, a molecule with the molecular formula C8H9NO2, which looks like this:

It is commonly used to treat mild to moderate pain and fever, and is used by both adults and children, but interestingly the evidence for its use to treat children is actually mixed. Some of its medical uses include fever, pain, headaches and osteoarthritis. How paracetamol works isn’t something that is often thought about, and despite being a commonly used medicine for over 100 years, it is a question that scientists don’t fully know the answer to. To understand how it is believed to work, we have to know what prostaglandins are. They are a family of tissue hormones which are produced as a response to injury or a few certain diseases. The most important function in this context is that they sensitize nerve endings so that when they are stimulated, we feel pain. The reason for this is it prevents us from doing further damage to this area. In order to reduce pain, paracetamol inhibits and therefore reduces these prostaglandins in the spinal cord, effectively increasing our pain tolerance so that we feel less pain. Similarly, to calm a fever, paracetamol affects the chemical messengers in the area of the brain which controls body temperature, the hypothalamic heat regulating centre.

The drug synthesized and tested before paracetamol was Acetanilide, the first medicine to have both analgesic (painkilling) and antipyretic (fever-reducing) effects, but it never hit the market due to its unacceptable toxic effects. Despite this, however, it prompted a search for a safer alternative drug with these same analgesic and antipyretic effects. Harmon Northrop Morse had

in fact already synthesized a paracetamol at John Hopkins University, but it wasn’t until 1887 that it was tested on humans by Joseph von Mering.

The image below shows Julius Axelrod, who along with Bernard Brodie, showed and explained that both Acetanilide and Phenacetin (another painkiller introduced in 1887 which was then removed from the market in the late 1960’s due to its association with renal diseases and cancers in the upper urinary tract) are metabolized to paracetamol (meaning when digested by the body, they are left as and used in this form), a drug with the same positive effects on the body but is better tolerated by the body, and therefore doesn’t have any of the same adverse side effects.

First produced in 1887, paracetamol was first clinically used in 1893, again by von Mering and then initially marketed in 1950 in the USA and 1956 in Australia and the UK under the name Panadol. However, when it was first marketed in the United States, it was sold as a mix of paracetamol, caffeine and aspirin called Triagesic. This was then removed from the market after, in 1951, three of its users were diagnosed with a blood disease called agranulocytosis, and it took several years to prove that the two were in fact completely unrelated. In the UK specifically, it has gained in popularity massively since being added to the British Pharmacopoeia in 1963 as an analgesic agent with few side effects.

Although Paracetamol is an over-the-counter medicine, there are 3 main risks and side effects involved with it, liver damage, skin reactions and asthma, and the presence of only 3 side effects makes Paracetamol a relatively safe drug to be using, as long as it is taken in the correct doses.

The most severe of these adverse effects is liver failure, which is generally only related to consuming an amount over the suggested dose. In 2013, the U.S. FDA (food and drug administration warned that acetaminophen may be linked to some very rare, but equally severe skin conditions such as acute generalised exanthematous pustulosis, an illness which occurs mostly in elderly people with significant comorbidities (the presence of multiple medical conditions). Finally, there is a casual relationship between paracetamol and the worsening of asthmatic symptoms, but the strength of this relationship is still a topic of debate today.

So while this drug is one used widely across the world, there is a surprising amount that we still don’t know about it, and following on from this, a general lack of understanding about what paracetamol is, what it does and its history, which is an important part of treating illness. Hopefully, awareness can be raised about paracetamol which can lead to its more effective use and the reduction of adverse effects or consequences which come alongside paracetamol’s many uses and benefits. Finally, I do think that paracetamol is as safe as we assume because the side effects are so rare I do believe that they are outweighed by the advantages.

LIGHTING UP YOUR SCREENS

HDTV, laptops, mobile phones, game systems. These windows bring us news, entertainment and our friends, not least during lockdown. The average young adult now spends over 4 hours a day on their phone alone, with these other forms of technology adding to that considerably.

Computers in the 1970s were monochromatic. This was perfectly good enough for business needs at the time with computers heavily used in industries such a banking, insurance, military and meterology. The first games were invented around the same time, including Pong on the Atari, (shown to the right). However this had limited popular appeal and computers were mostly used at work, taking up whole rooms of office buildings. Until games could be displayed in the best way possible, there was no market for consumers and the most creative individuals worked in film, music and art rather than gaming.

This all changed thanks to IBM Chief Engineer Mark Dean and his team. Vital inventions which were necessary to make computers accessible at home, included the ‘Industry Standard Architecture’ systems bus, a slot that was almost an early day USB. This allowed personal computers to be modified with additions including memory drives, printers and monitors which could be adapted

with new purchases. This created significant benefits in their ease of use. No longer would you need your own engineer as office computers required and technology could be seamlessly upgraded by the early adopters as new developments took place.

His next big invention, the colour graphics adapter was the first to enable the colour screen and has become the standard for later technology. This is integrated into the central processing unit and converts data and information into RGBI colour instructions for the screen to display. In the lowest resolution format, this allowed for a choice of 16 colours as shown in the image of Pakuman –the forerunner of Pac-Man. Each colour is given a 4 bit code, with the first three referring to red, green and blue components, and the final bit intensifying the brightness (for instance to go from light blue to blue or dark grey to black). The monitor

then converts the four bit value to a range of voltages between 0 and 1 with each impulse triggering the specified colour to that part of the screen.

The function of the screen at this time was that this voltage was fired as electron beams fired from the back of the monitor towards each pixel simultaneously. The pixels would contain quantities of phosphors, which are chemicals that can fluoresce when exposed to radiation. Their electrons are excited to a higher energy state and as they return, the energy is emitted as a wavelength of visible colour. By each pixel on the back of the screen having three different phosphors, with each emitting a different characteristic wavelength of light from the red, green or blue sections of the visible light spectrum, it became possible to produce colour images from a digital input on a home computer for the first time.

Without the invention of the colour graphics adapter and the colour monitor, it is not possible to see the development of so many new technologies. It was no surprise that the computer game industry exploded in the 1980s, both in arcade machines and the first gaming creations by Nintendo and Sega. The rise of personal computers and the 90s dominance of Microsoft and the return of Apple could be driven by screens. These have become portable in the form of laptops, tablets and mobile phones, whilst into the last decade, it is probably televisions that has seen the greatest innovation with flat screens, LCD and 8k TVs offering up to 67 Mega pixels of resolution – 4000 times the detail of that available from Mark Dean’s Mark demonstrated the benefits of curiosity and creativity in his own practice, trying to build things and make things work even from a young age. This included building a tractor with his father whilst still a child. He also advocated for the benefits of a diverse workforce. The tech industry is highly homogenous. Only 5% of google’s workforce being black or Hispanic when these populations make up 43% of the population of California, the base for its HQ. Mark advocated that there are a huge number of benefits through having a broader awareness of social norms, more innovative thinking and understanding a range of markets both by country and by groups in society.

A significant proportion of the way we spend our time is, for better and worse, glued to these screens, building on the invention of the 1980s. Though mostly domestic in use, it has clearly been revolutionary for the way so many of us now live.