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  • Air conditioning

    Air conditioning, often abbreviated as A/C (US) or air con (UK),[1] is the process of removing heat from an enclosed space to achieve a more comfortable interior temperature and in some cases also controlling the humidity of internal air. Air conditioning can be achieved using a mechanical ‘air conditioner’ or by other methods, including passive cooling and ventilative cooling.[2][3] Air conditioning is a member of a family of systems and techniques that provide heating, ventilation, and air conditioning (HVAC).[4] Heat pumps are similar in many ways to air conditioners, but use a reversing valve to allow them both to heat and to cool an enclosed space.[5]

    Air conditioners, which typically use vapor-compression refrigeration, range in size from small units used in vehicles or single rooms to massive units that can cool large buildings.[6] Air source heat pumps, which can be used for heating as well as cooling, are becoming increasingly common in cooler climates.

    Air conditioners can reduce mortality rates due to higher temperature.[7] According to the International Energy Agency (IEA) 1.6 billion air conditioning units were used globally in 2016.[8] The United Nations called for the technology to be made more sustainable to mitigate climate change and for the use of alternatives, like passive cooling, evaporative cooling, selective shading, windcatchers, and better thermal insulation.

    History

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    Air conditioning dates back to prehistory.[9] Double-walled living quarters, with a gap between the two walls to encourage air flow, were found in the ancient city of Hamoukar, in modern Syria.[10] Ancient Egyptian buildings also used a wide variety of passive air-conditioning techniques.[11] These became widespread from the Iberian Peninsula through North Africa, the Middle East, and Northern India.[12]

    Passive techniques remained widespread until the 20th century when they fell out of fashion and were replaced by powered air conditioning. Using information from engineering studies of traditional buildings, passive techniques are being revived and modified for 21st-century architectural designs.[13][12]

    An array of air conditioner condenser units outside a commercial office building

    Air conditioners allow the building’s indoor environment to remain relatively constant, largely independent of changes in external weather conditions and internal heat loads. They also enable deep plan buildings to be created and have allowed people to live comfortably in hotter parts of the world.[14]

    Development

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    Preceding discoveries

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    In 1558, Giambattista della Porta described a method of chilling ice to temperatures far below its freezing point by mixing it with potassium nitrate (then called “nitre”) in his popular science book Natural Magic.[15][16][17] In 1620, Cornelis Drebbel demonstrated “Turning Summer into Winter” for James I of England, chilling part of the Great Hall of Westminster Abbey with an apparatus of troughs and vats.[18] Drebbel’s contemporary Francis Bacon, like della Porta a believer in science communication, may not have been present at the demonstration, but in a book published later the same year, he described it as “experiment of artificial freezing” and said that “Nitre (or rather its spirit) is very cold, and hence nitre or salt when added to snow or ice intensifies the cold of the latter, the nitre by adding to its cold, but the salt by supplying activity to the cold of the snow.”[15]

    In 1758, Benjamin Franklin and John Hadley, a chemistry professor at the University of Cambridge, conducted experiments applying the principle of evaporation as a means to cool an object rapidly. Franklin and Hadley confirmed that the evaporation of highly volatile liquids (such as alcohol and ether) could be used to drive down the temperature of an object past the freezing point of water. They experimented with the bulb of a mercury-in-glass thermometer as their object. They used a bellows to speed up the evaporation. They lowered the temperature of the thermometer bulb down to −14 °C (7 °F) while the ambient temperature was 18 °C (64 °F). Franklin noted that soon after they passed the freezing point of water 0 °C (32 °F), a thin film of ice formed on the surface of the thermometer’s bulb and that the ice mass was about 6 mm (14 in) thick when they stopped the experiment upon reaching −14 °C (7 °F). Franklin concluded: “From this experiment, one may see the possibility of freezing a man to death on a warm summer’s day.”[19]

    The 19th century included many developments in compression technology. In 1820, English scientist and inventor Michael Faraday discovered that compressing and liquefying ammonia could chill air when the liquefied ammonia was allowed to evaporate.[20] In 1842, Florida physician John Gorrie used compressor technology to create ice, which he used to cool air for his patients in his hospital in Apalachicola, Florida. He hoped to eventually use his ice-making machine to regulate the temperature of buildings.[20][21] He envisioned centralized air conditioning that could cool entire cities. Gorrie was granted a patent in 1851,[22] but following the death of his main backer, he was not able to realize his invention.[23] In 1851, James Harrison created the first mechanical ice-making machine in Geelong, Australia, and was granted a patent for an ether vapor-compression refrigeration system in 1855 that produced three tons of ice per day.[24] In 1860, Harrison established a second ice company. He later entered the debate over competing against the American advantage of ice-refrigerated beef sales to the United Kingdom.[24]

    First devices

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    Willis Carrier, who is credited with building the first modern electrical air conditioning unit

    Electricity made the development of effective units possible. In 1901, American inventor Willis H. Carrier built what is considered the first modern electrical air conditioning unit.[25][26][27][28] In 1902, he installed his first air-conditioning system, in the Sackett-Wilhelms Lithographing & Publishing Company in Brooklyn, New York.[29] His invention controlled both the temperature and humidity, which helped maintain consistent paper dimensions and ink alignment at the printing plant. Later, together with six other employees, Carrier formed The Carrier Air Conditioning Company of America, a business that in 2020 employed 53,000 people and was valued at $18.6 billion.[30][31]

    In 1906, Stuart W. Cramer of Charlotte, North Carolina, was exploring ways to add moisture to the air in his textile mill. Cramer coined the term “air conditioning” in a patent claim which he filed that year, where he suggested that air conditioning was analogous to “water conditioning”, then a well-known process for making textiles easier to process.[32] He combined moisture with ventilation to “condition” and change the air in the factories; thus, controlling the humidity that is necessary in textile plants. Willis Carrier adopted the term and incorporated it into the name of his company.[33]

    Domestic air conditioning soon took off. In 1914, the first domestic air conditioning was installed in Minneapolis in the home of Charles Gilbert Gates. It is, however, possible that the considerable device (c. 2.1 m × 1.8 m × 6.1 m; 7 ft × 6 ft × 20 ft) was never used, as the house remained uninhabited[20] (Gates had already died in October 1913.)

    In 1931, H.H. Schultz and J.Q. Sherman developed what would become the most common type of individual room air conditioner: one designed to sit on a window ledge. The units went on sale in 1932 at US$10,000 to $50,000 (the equivalent of $200,000 to $1,200,000 in 2024.)[20] A year later, the first air conditioning systems for cars were offered for sale.[34] Chrysler Motors introduced the first practical semi-portable air conditioning unit in 1935,[35] and Packard became the first automobile manufacturer to offer an air conditioning unit in its cars in 1939.[36]

    Further development

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    Innovations in the latter half of the 20th century allowed more ubiquitous air conditioner use. In 1945, Robert Sherman of Lynn, Massachusetts, invented a portable, in-window air conditioner that cooled, heated, humidified, dehumidified, and filtered the air.[37] The first inverter air conditioners were released in 1980–1981.[38][39]

    In 1954, Ned Cole, a 1939 architecture graduate from the University of Texas at Austin, developed the first experimental “suburb” with inbuilt air conditioning in each house. 22 homes were developed on a flat, treeless track in northwest Austin, Texas, and the community was christened the ‘Austin Air-Conditioned Village.’ The residents were subjected to a year-long study of the effects of air conditioning led by the nation’s premier air conditioning companies, builders, and social scientists. In addition, researchers from UT’s Health Service and Psychology Department studied the effects on the “artificially cooled humans.” One of the more amusing discoveries was that each family reported being troubled with scorpions, the leading theory being that scorpions sought cool, shady places. Other reported changes in lifestyle were that mothers baked more, families ate heavier foods, and they were more apt to choose hot drinks.[40][41]

    Air conditioner adoption tends to increase above around $10,000 annual household income in warmer areas.[42] Global GDP growth explains around 85% of increased air condition adoption by 2050, while the remaining 15% can be explained by climate change.[42]

    As of 2016 an estimated 1.6 billion air conditioning units were used worldwide, with over half of them in China and USA, and a total cooling capacity of 11,675 gigawatts.[8][43] The International Energy Agency predicted in 2018 that the number of air conditioning units would grow to around 4 billion units by 2050 and that the total cooling capacity would grow to around 23,000 GW, with the biggest increases in India and China.[8] Between 1995 and 2004, the proportion of urban households in China with air conditioners increased from 8% to 70%.[44] As of 2015, nearly 100 million homes, or about 87% of US households, had air conditioning systems.[45] In 2019, it was estimated that 90% of new single-family homes constructed in the US included air conditioning (ranging from 99% in the South to 62% in the West).[46][47]

    Operation

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    Operating principles

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    Main article: Vapor-compression refrigeration

    A simple stylized diagram of the refrigeration cycle: 1) condensing coil, 2) expansion valve, 3) evaporator coil, 4) compressor

    Cooling in traditional air conditioner systems is accomplished using the vapor-compression cycle, which uses a refrigerant’s forced circulation and phase change between gas and liquid to transfer heat.[48][49] The vapor-compression cycle can occur within a unitary, or packaged piece of equipment; or within a chiller that is connected to terminal cooling equipment (such as a fan coil unit in an air handler) on its evaporator side and heat rejection equipment such as a cooling tower on its condenser side. An air source heat pump shares many components with an air conditioning system, but includes a reversing valve, which allows the unit to be used to heat as well as cool a space.[50]

    Air conditioning equipment will reduce the absolute humidity of the air processed by the system if the surface of the evaporator coil is significantly cooler than the dew point of the surrounding air. An air conditioner designed for an occupied space will typically achieve a 30% to 60% relative humidity in the occupied space.[51]

    Most modern air-conditioning systems feature a dehumidification cycle during which the compressor runs. At the same time, the fan is slowed to reduce the evaporator temperature and condense more water. A dehumidifier uses the same refrigeration cycle but incorporates both the evaporator and the condenser into the same air path; the air first passes over the evaporator coil, where it is cooled[52] and dehumidified before passing over the condenser coil, where it is warmed again before it is released back into the room.[citation needed]

    Free cooling can sometimes be selected when the external air is cooler than the internal air. Therefore, the compressor does not need to be used, resulting in high cooling efficiencies for these times. This may also be combined with seasonal thermal energy storage.[53]

    Heating

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    Main article: Heat pump

    Some air conditioning systems can reverse the refrigeration cycle and act as an air source heat pump, thus heating instead of cooling the indoor environment. They are also commonly referred to as “reverse cycle air conditioners”. The heat pump is significantly more energy-efficient than electric resistance heating, because it moves energy from air or groundwater to the heated space and the heat from purchased electrical energy. When the heat pump is in heating mode, the indoor evaporator coil switches roles and becomes the condenser coil, producing heat. The outdoor condenser unit also switches roles to serve as the evaporator and discharges cold air (colder than the ambient outdoor air).

    Most air source heat pumps become less efficient in outdoor temperatures lower than 4 °C or 40 °F.[54] This is partly because ice forms on the outdoor unit’s heat exchanger coil, which blocks air flow over the coil. To compensate for this, the heat pump system must temporarily switch back into the regular air conditioning mode to switch the outdoor evaporator coil back to the condenser coil, to heat up and defrost. Therefore, some heat pump systems will have electric resistance heating in the indoor air path that is activated only in this mode to compensate for the temporary indoor air cooling, which would otherwise be uncomfortable in the winter.

    Newer models have improved cold-weather performance, with efficient heating capacity down to −14 °F (−26 °C).[55][54][56] However, there is always a chance that the humidity that condenses on the heat exchanger of the outdoor unit could freeze, even in models that have improved cold-weather performance, requiring a defrosting cycle to be performed.

    The icing problem becomes much more severe with lower outdoor temperatures, so heat pumps are sometimes installed in tandem with a more conventional form of heating, such as an electrical heater, a natural gasheating oil, or wood-burning fireplace or central heating, which is used instead of or in addition to the heat pump during harsher winter temperatures. In this case, the heat pump is used efficiently during milder temperatures, and the system is switched to the conventional heat source when the outdoor temperature is lower.

    Performance

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    Main articles: coefficient of performanceSeasonal energy efficiency ratio, and European seasonal energy efficiency ratio

    The coefficient of performance (COP) of an air conditioning system is a ratio of useful heating or cooling provided to the work required.[57][58] Higher COPs equate to lower operating costs. The COP usually exceeds 1; however, the exact value is highly dependent on operating conditions, especially absolute temperature and relative temperature between sink and system, and is often graphed or averaged against expected conditions.[59] Air conditioner equipment power in the U.S. is often described in terms of “tons of refrigeration“, with each approximately equal to the cooling power of one short ton (2,000 pounds (910 kg) of ice melting in a 24-hour period. The value is equal to 12,000 BTUIT per hour, or 3,517 watts.[60] Residential central air systems are usually from 1 to 5 tons (3.5 to 18 kW) in capacity.[citation needed]

    The efficiency of air conditioners is often rated by the seasonal energy efficiency ratio (SEER), which is defined by the Air Conditioning, Heating and Refrigeration Institute in its 2008 standard AHRI 210/240, Performance Rating of Unitary Air-Conditioning and Air-Source Heat Pump Equipment.[61] A similar standard is the European seasonal energy efficiency ratio (ESEER).[citation needed]

    Efficiency is strongly affected by the humidity of the air to be cooled. Dehumidifying the air before attempting to cool it can reduce subsequent cooling costs by as much as 90 percent. Thus, reducing dehumidifying costs can materially affect overall air conditioning costs.[62]

    Control system

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    Wireless remote control

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    Main articles: Remote control and Infrared blaster

    A wireless remote controller

    The infrared transmitting LED on the remote

    The infrared receiver on the air conditioner

    This type of controller uses an infrared LED to relay commands from a remote control to the air conditioner. The output of the infrared LED (like that of any infrared remote) is invisible to the human eye because its wavelength is beyond the range of visible light (940 nm). This system is commonly used on mini-split air conditioners because it is simple and portable. Some window and ducted central air conditioners uses it as well.

    Wired controller

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    Main article: Thermostat

    Several wired controllers (Indonesia, 2024)

    A wired controller, also called a “wired thermostat,” is a device that controls an air conditioner by switching heating or cooling on or off. It uses different sensors to measure temperatures and actuate control operations. Mechanical thermostats commonly use bimetallic strips, converting a temperature change into mechanical displacement, to actuate control of the air conditioner. Electronic thermostats, instead, use a thermistor or other semiconductor sensor, processing temperature change as electronic signals to control the air conditioner.

    These controllers are usually used in hotel rooms because they are permanently installed into a wall and hard-wired directly into the air conditioner unit, eliminating the need for batteries.

    Types

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    TypesTypical Capacity*Air supplyMountingTypical application
    Mini-splitsmall – largeDirectWallResidential
    Windowvery small – smallDirectWindowResidential
    Portablevery small – smallDirect / DuctedFloorResidential, remote areas
    Ducted (individual)small – very largeDuctedCeilingResidential, commercial
    Ducted (central)medium – very largeDuctedCeilingResidential, commercial
    Ceiling suspendedmedium – largeDirectCeilingCommercial
    Cassettemedium – largeDirect / DuctedCeilingCommercial
    Floor standingmedium – largeDirect / DuctedFloorCommercial
    Packagedvery largeDirect / DuctedFloorCommercial
    Packaged RTU (Rooftop Unit)very largeDuctedRooftopCommercial

    * where the typical capacity is in kilowatt as follows:

    • very small: <1.5 kW
    • small: 1.5–3.5 kW
    • medium: 4.2–7.1 kW
    • large: 7.2–14 kW
    • very large: >14 kW

    Mini-split and multi-split systems

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    Evaporator, indoor unit, or terminal, side of a ductless split-type air conditioner

    Ductless systems (often mini-split, though there are now ducted mini-split) typically supply conditioned and heated air to a single or a few rooms of a building, without ducts and in a decentralized manner.[63] Multi-zone or multi-split systems are a common application of ductless systems and allow up to eight rooms (zones or locations) to be conditioned independently from each other, each with its indoor unit and simultaneously from a single outdoor unit.

    The first mini-split system was sold in 1961 by Toshiba in Japan, and the first wall-mounted mini-split air conditioner was sold in 1968 in Japan by Mitsubishi Electric, where small home sizes motivated their development. The Mitsubishi model was the first air conditioner with a cross-flow fan.[64][65][66] In 1969, the first mini-split air conditioner was sold in the US.[67] Multi-zone ductless systems were invented by Daikin in 1973, and variable refrigerant flow systems (which can be thought of as larger multi-split systems) were also invented by Daikin in 1982. Both were first sold in Japan.[68] Variable refrigerant flow systems when compared with central plant cooling from an air handler, eliminate the need for large cool air ducts, air handlers, and chillers; instead cool refrigerant is transported through much smaller pipes to the indoor units in the spaces to be conditioned, thus allowing for less space above dropped ceilings and a lower structural impact, while also allowing for more individual and independent temperature control of spaces. The outdoor and indoor units can be spread across the building.[69] Variable refrigerant flow indoor units can also be turned off individually in unused spaces.[citation needed] The lower start-up power of VRF’s DC inverter compressors and their inherent DC power requirements also allow VRF solar-powered heat pumps to be run using DC-providing solar panels.

    Ducted central systems

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    Split-system central air conditioners consist of two heat exchangers, an outside unit (the condenser) from which heat is rejected to the environment and an internal heat exchanger (the evaporator, or Fan Coil Unit, FCU) with the piped refrigerant being circulated between the two. The FCU is then connected to the spaces to be cooled by ventilation ducts.[70] Floor standing air conditioners are similar to this type of air conditioner but sit within spaces that need cooling.

    Central plant cooling

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    See also: Chiller

    Industrial air conditioners on top of the shopping mall Passage in Linz, Austria

    Large central cooling plants may use intermediate coolant such as chilled water pumped into air handlers or fan coil units near or in the spaces to be cooled which then duct or deliver cold air into the spaces to be conditioned, rather than ducting cold air directly to these spaces from the plant, which is not done due to the low density and heat capacity of air, which would require impractically large ducts. The chilled water is cooled by chillers in the plant, which uses a refrigeration cycle to cool water, often transferring its heat to the atmosphere even in liquid-cooled chillers through the use of cooling towers. Chillers may be air- or liquid-cooled.[71][72]

    Portable units

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    A portable system has an indoor unit on wheels connected to an outdoor unit via flexible pipes, similar to a permanently fixed installed unit (such as a ductless split air conditioner).

    Hose systems, which can be monoblock or air-to-air, are vented to the outside via air ducts. The monoblock type collects the water in a bucket or tray and stops when full. The air-to-air type re-evaporates the water, discharges it through the ducted hose, and can run continuously. Many but not all portable units draw indoor air and expel it outdoors through a single duct, negatively impacting their overall cooling efficiency.

    Many portable air conditioners come with heat as well as a dehumidification function.[73]

    Window unit and packaged terminal

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    Through-the-wall PTAC units, University Motor Inn, Philadelphia

    Main article: Packaged terminal air conditioner

    The packaged terminal air conditioner (PTAC), through-the-wall, and window air conditioners are similar. These units are installed on a window frame or on a wall opening. The unit usually has an internal partition separating its indoor and outdoor sides, which contain the unit’s condenser and evaporator, respectively. PTAC systems may be adapted to provide heating in cold weather, either directly by using an electric strip, gas, or other heaters, or by reversing the refrigerant flow to heat the interior and draw heat from the exterior air, converting the air conditioner into a heat pump. They may be installed in a wall opening with the help of a special sleeve on the wall and a custom grill that is flush with the wall and window air conditioners can also be installed in a window, but without a custom grill.[74]

    Packaged air conditioner

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    Packaged air conditioners (also known as self-contained units)[75][76] are central systems that integrate into a single housing all the components of a split central system, and deliver air, possibly through ducts, to the spaces to be cooled. Depending on their construction they may be outdoors or indoors, on roofs (rooftop units),[77][78] draw the air to be conditioned from inside or outside a building and be water or air-cooled. Often, outdoor units are air-cooled while indoor units are liquid-cooled using a cooling tower.[70][79][80][81][82][83]

    Types of compressors

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    Compressor typesCommon applicationsTypical capacityEfficiencyDurabilityRepairability
    ReciprocatingRefrigeratorWalk-in freezer, portable air conditionerssmall – largevery low (small capacity)medium (large capacity)very lowmedium
    Rotary vaneResidential mini splitssmalllowloweasy
    ScrollCommercial and central systems, VRFmediummediummediumeasy
    Rotary screwCommercial chillermedium – largemediummediumhard
    CentrifugalCommercial chillervery largemediumhighhard
    Maglev CentrifugalCommercial chillervery largehighvery highvery hard

    Reciprocating

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    Main article: Reciprocating compressor

    This compressor consists of a crankcasecrankshaftpiston rodpistonpiston ringcylinder head and valves. [citation needed]

    Scroll

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    Main article: Scroll compressor

    This compressor uses two interleaving scrolls to compress the refrigerant.[84] it consists of one fixed and one orbiting scrolls. This type of compressor is more efficient because it has 70 percent less moving parts than a reciprocating compressor. [citation needed]

    Screw

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    Main article: Rotary-screw compressor

    This compressor use two very closely meshing spiral rotors to compress the gas. The gas enters at the suction side and moves through the threads as the screws rotate. The meshing rotors force the gas through the compressor, and the gas exits at the end of the screws. The working area is the inter-lobe volume between the male and female rotors. It is larger at the intake end, and decreases along the length of the rotors until the exhaust port. This change in volume is the compression. [citation needed]

    Capacity modulation technologies

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    There are several ways to modulate the cooling capacity in refrigeration or air conditioning and heating systems. The most common in air conditioning are: on-off cycling, hot gas bypass, use or not of liquid injection, manifold configurations of multiple compressors, mechanical modulation (also called digital), and inverter technology. [citation needed]

    Hot gas bypass

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    Hot gas bypass involves injecting a quantity of gas from discharge to the suction side. The compressor will keep operating at the same speed, but due to the bypass, the refrigerant mass flow circulating with the system is reduced, and thus the cooling capacity. This naturally causes the compressor to run uselessly during the periods when the bypass is operating. The turn down capacity varies between 0 and 100%.[85]

    Manifold configurations

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    Several compressors can be installed in the system to provide the peak cooling capacity. Each compressor can run or not in order to stage the cooling capacity of the unit. The turn down capacity is either 0/33/66 or 100% for a trio configuration and either 0/50 or 100% for a tandem.[citation needed]

    Mechanically modulated compressor

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    This internal mechanical capacity modulation is based on periodic compression process with a control valve, the two scroll set move apart stopping the compression for a given time period. This method varies refrigerant flow by changing the average time of compression, but not the actual speed of the motor. Despite an excellent turndown ratio – from 10 to 100% of the cooling capacity, mechanically modulated scrolls have high energy consumption as the motor continuously runs.[citation needed]

    Variable-speed compressor

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    Main article: Inverter compressor

    This system uses a variable-frequency drive (also called an Inverter) to control the speed of the compressor. The refrigerant flow rate is changed by the change in the speed of the compressor. The turn down ratio depends on the system configuration and manufacturer. It modulates from 15 or 25% up to 100% at full capacity with a single inverter from 12 to 100% with a hybrid tandem. This method is the most efficient way to modulate an air conditioner’s capacity. It is up to 58% more efficient than a fixed speed system.[citation needed]

    Impact

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    Health effects

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    Rooftop condenser unit fitted on top of an Osaka Municipal Subway 10 series subway carriage. Air conditioning has become increasingly prevalent on public transport vehicles as a form of climate control, and to ensure passenger comfort and drivers’ occupational safety and health.

    In hot weather, air conditioning can prevent heat strokedehydration due to excessive sweatingelectrolyte imbalancekidney failure, and other issues due to hyperthermia.[8][86] Heat waves are the most lethal type of weather phenomenon in the United States.[87][88] A 2020 study found that areas with lower use of air conditioning correlated with higher rates of heat-related mortality and hospitalizations.[89] The August 2003 France heatwave resulted in approximately 15,000 deaths, where 80% of the victims were over 75 years old. In response, the French government required all retirement homes to have at least one air-conditioned room at 25 °C (77 °F) per floor during heatwaves.[8]

    Air conditioning (including filtration, humidification, cooling and disinfection) can be used to provide a clean, safe, hypoallergenic atmosphere in hospital operating rooms and other environments where proper atmosphere is critical to patient safety and well-being. It is sometimes recommended for home use by people with allergies, especially mold.[90][91] However, poorly maintained water cooling towers can promote the growth and spread of microorganisms such as Legionella pneumophila, the infectious agent responsible for Legionnaires’ disease. As long as the cooling tower is kept clean (usually by means of a chlorine treatment), these health hazards can be avoided or reduced. The state of New York has codified requirements for registration, maintenance, and testing of cooling towers to protect against Legionella.[92]

    Economic effects

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    First designed to benefit targeted industries such as the press as well as large factories, the invention quickly spread to public agencies and administrations with studies with claims of increased productivity close to 24% in places equipped with air conditioning.[93]

    Air conditioning caused various shifts in demography, notably that of the United States starting from the 1970s. In the US, the birth rate was lower in the spring than during other seasons until the 1970s but this difference then declined since then.[94] As of 2007, the Sun Belt contained 30% of the total US population while it was inhabited by 24% of Americans at the beginning of the 20th century.[95] Moreover, the summer mortality rate in the US, which had been higher in regions subject to a heat wave during the summer, also evened out.[7]

    The spread of the use of air conditioning acts as a main driver for the growth of global demand of electricity.[96] According to a 2018 report from the International Energy Agency (IEA), it was revealed that the energy consumption for cooling in the United States, involving 328 million Americans, surpasses the combined energy consumption of 4.4 billion people in Africa, Latin America, the Middle East, and Asia (excluding China).[8] A 2020 survey found that an estimated 88% of all US households use AC, increasing to 93% when solely looking at homes built between 2010 and 2020.[97]

    Environmental effects

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    Air conditioner farm in the facade of a building in Singapore

    Space cooling including air conditioning accounted globally for 2021 terawatt-hours of energy usage in 2016 with around 99% in the form of electricity, according to a 2018 report on air-conditioning efficiency by the International Energy Agency.[8] The report predicts an increase of electricity usage due to space cooling to around 6200 TWh by 2050,[8][98] and that with the progress currently seen, greenhouse gas emissions attributable to space cooling will double: 1,135 million tons (2016) to 2,070 million tons.[8] There is some push to increase the energy efficiency of air conditioners. United Nations Environment Programme (UNEP) and the IEA found that if air conditioners could be twice as effective as now, 460 billion tons of GHG could be cut over 40 years.[99] The UNEP and IEA also recommended legislation to decrease the use of hydrofluorocarbons, better building insulation, and more sustainable temperature-controlled food supply chains going forward.[99]

    Refrigerants have also caused and continue to cause serious environmental issues, including ozone depletion and climate change, as several countries have not yet ratified the Kigali Amendment to reduce the consumption and production of hydrofluorocarbons.[100] CFCs and HCFCs refrigerants such as R-12 and R-22, respectively, used within air conditioners have caused damage to the ozone layer,[101] and hydrofluorocarbon refrigerants such as R-410A and R-404A, which were designed to replace CFCs and HCFCs, are instead exacerbating climate change.[102] Both issues happen due to the venting of refrigerant to the atmosphere, such as during repairs. HFO refrigerants, used in some if not most new equipment, solve both issues with an ozone damage potential (ODP) of zero and a much lower global warming potential (GWP) in the single or double digits vs. the three or four digits of hydrofluorocarbons.[103]

    Hydrofluorocarbons would have raised global temperatures by around 0.3–0.5 °C (0.5–0.9 °F) by 2100 without the Kigali Amendment. With the Kigali Amendment, the increase of global temperatures by 2100 due to hydrofluorocarbons is predicted to be around 0.06 °C (0.1 °F).[104]

    Alternatives to continual air conditioning include passive cooling, passive solar cooling, natural ventilation, operating shades to reduce solar gain, using trees, architectural shades, windows (and using window coatings) to reduce solar gain.[citation needed]

    Social effects

    [edit]

    Socioeconomic groups with a household income below around $10,000 tend to have a low air conditioning adoption,[42] which worsens heat-related mortality.[7] The lack of cooling can be hazardous, as areas with lower use of air conditioning correlate with higher rates of heat-related mortality and hospitalizations.[89] Premature mortality in NYC is projected to grow between 47% and 95% in 30 years, with lower-income and vulnerable populations most at risk.[89] Studies on the correlation between heat-related mortality and hospitalizations and living in low socioeconomic locations can be traced in Phoenix, Arizona,[105] Hong Kong,[106] China,[106] Japan,[107] and Italy.[108][109] Additionally, costs concerning health care can act as another barrier, as the lack of private health insurance during a 2009 heat wave in Australia, was associated with heat-related hospitalization.[109]

    Disparities in socioeconomic status and access to air conditioning are connected by some to institutionalized racism, which leads to the association of specific marginalized communities with lower economic status, poorer health, residing in hotter neighborhoods, engaging in physically demanding labor, and experiencing limited access to cooling technologies such as air conditioning.[109] A study overlooking Chicago, Illinois, Detroit, and Michigan found that black households were half as likely to have central air conditioning units when compared to their white counterparts.[110] Especially in cities, Redlining creates heat islands, increasing temperatures in certain parts of the city.[109] This is due to materials heat-absorbing building materials and pavements and lack of vegetation and shade coverage.[111] There have been initiatives that provide cooling solutions to low-income communities, such as public cooling spaces.[8][111]

    Other techniques

    [edit]

    Buildings designed with passive air conditioning are generally less expensive to construct and maintain than buildings with conventional HVAC systems with lower energy demands.[112] While tens of air changes per hour, and cooling of tens of degrees, can be achieved with passive methods, site-specific microclimate must be taken into account, complicating building design.[12]

    Many techniques can be used to increase comfort and reduce the temperature in buildings. These include evaporative cooling, selective shading, wind, thermal convection, and heat storage.[113]

    Passive ventilation

    [edit]

    This section is an excerpt from Passive ventilation.[edit]

    The ventilation system of a regular earthship
    Dogtrot houses are designed to maximise natural ventilation.
    roof turbine ventilator, colloquially known as a ‘Whirly Bird’ is an application of wind driven ventilation.

    Passive ventilation is the process of supplying air to and removing air from an indoor space without using mechanical systems. It refers to the flow of external air to an indoor space as a result of pressure differences arising from natural forces.

    There are two types of natural ventilation occurring in buildings: wind driven ventilation and buoyancy-driven ventilation. Wind driven ventilation arises from the different pressures created by wind around a building or structure, and openings being formed on the perimeter which then permit flow through the building. Buoyancy-driven ventilation occurs as a result of the directional buoyancy force that results from temperature differences between the interior and exterior.[114]Since the internal heat gains which create temperature differences between the interior and exterior are created by natural processes, including the heat from people, and wind effects are variable, naturally ventilated buildings are sometimes called “breathing buildings”.

    Passive cooling

    [edit]

    This section is an excerpt from Passive cooling.[edit]

    A traditional Iranian solar cooling design using a wind tower

    Passive cooling is a building design approach that focuses on heat gain control and heat dissipation in a building in order to improve the indoor thermal comfort with low or no energy consumption.[115][116] This approach works either by preventing heat from entering the interior (heat gain prevention) or by removing heat from the building (natural cooling).[117]

    Natural cooling utilizes on-site energy, available from the natural environment, combined with the architectural design of building components (e.g. building envelope), rather than mechanical systems to dissipate heat.[118] Therefore, natural cooling depends not only on the architectural design of the building but on how the site’s natural resources are used as heat sinks (i.e. everything that absorbs or dissipates heat). Examples of on-site heat sinks are the upper atmosphere (night sky), the outdoor air (wind), and the earth/soil.Passive cooling is an important tool for design of buildings for climate change adaptation – reducing dependency on energy-intensive air conditioning in warming environments.[119][120]

    A pair of short windcatchers (malqaf) used in traditional architecture; wind is forced down on the windward side and leaves on the leeward side (cross-ventilation). In the absence of wind, the circulation can be driven with evaporative cooling in the inlet (which is also designed to catch dust). In the center, a shuksheika (roof lantern vent), used to shade the qa’a below while allowing hot air rise out of it (stack effect).[11]

    Daytime radiative cooling

    [edit]

    Passive daytime radiative cooling (PDRC) surfaces are high in solar reflectance and heat emittance, cooling with zero energy use or pollution.[121]

    Passive daytime radiative cooling (PDRC) surfaces reflect incoming solar radiation and heat back into outer space through the infrared window for cooling during the daytime. Daytime radiative cooling became possible with the ability to suppress solar heating using photonic structures, which emerged through a study by Raman et al. (2014).[122] PDRCs can come in a variety of forms, including paint coatings and films, that are designed to be high in solar reflectance and thermal emittance.[121][123]

    PDRC applications on building roofs and envelopes have demonstrated significant decreases in energy consumption and costs.[123] In suburban single-family residential areas, PDRC application on roofs can potentially lower energy costs by 26% to 46%.[124] PDRCs are predicted to show a market size of ~$27 billion for indoor space cooling by 2025 and have undergone a surge in research and development since the 2010s.[125][126]

    Fans

    [edit]

    Main article: Ceiling fan

    Hand fans have existed since prehistory. Large human-powered fans built into buildings include the punkah.

    The 2nd-century Chinese inventor Ding Huan of the Han dynasty invented a rotary fan for air conditioning, with seven wheels 3 m (10 ft) in diameter and manually powered by prisoners.[127]: 99, 151, 233  In 747, Emperor Xuanzong (r. 712–762) of the Tang dynasty (618–907) had the Cool Hall (Liang Dian 涼殿) built in the imperial palace, which the Tang Yulin describes as having water-powered fan wheels for air conditioning as well as rising jet streams of water from fountains. During the subsequent Song dynasty (960–1279), written sources mentioned the air conditioning rotary fan as even more widely used.[127]: 134, 151 

    Thermal buffering

    [edit]

    In areas that are cold at night or in winter, heat storage is used. Heat may be stored in earth or masonry; air is drawn past the masonry to heat or cool it.[13]

    In areas that are below freezing at night in winter, snow and ice can be collected and stored in ice houses for later use in cooling.[13] This technique is over 3,700 years old in the Middle East.[128] Harvesting outdoor ice during winter and transporting and storing for use in summer was practiced by wealthy Europeans in the early 1600s,[15] and became popular in Europe and the Americas towards the end of the 1600s.[129] This practice was replaced by mechanical compression-cycle icemakers.

    Evaporative cooling

    [edit]

    Main article: Evaporative cooler

    An evaporative cooler

    In dry, hot climates, the evaporative cooling effect may be used by placing water at the air intake, such that the draft draws air over water and then into the house. For this reason, it is sometimes said that the fountain, in the architecture of hot, arid climates, is like the fireplace in the architecture of cold climates.[11] Evaporative cooling also makes the air more humid, which can be beneficial in a dry desert climate.[130]

    Evaporative coolers tend to feel as if they are not working during times of high humidity, when there is not much dry air with which the coolers can work to make the air as cool as possible for dwelling occupants. Unlike other types of air conditioners, evaporative coolers rely on the outside air to be channeled through cooler pads that cool the air before it reaches the inside of a house through its air duct system; this cooled outside air must be allowed to push the warmer air within the house out through an exhaust opening such as an open door or window.

  • Aspirin 

    Aspirin is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce painfever, and inflammation, and as an antithrombotic.[11] Specific inflammatory conditions that aspirin is used to treat include Kawasaki diseasepericarditis, and rheumatic fever.[11]

    Aspirin is also used long-term to help prevent further heart attacksischaemic strokes, and blood clots in people at high risk.[11] For pain or fever, effects typically begin within 30 minutes.[11] Aspirin works similarly to other NSAIDs but also suppresses the normal functioning of platelets.[11]

    One common adverse effect is an upset stomach.[11] More significant side effects include stomach ulcersstomach bleeding, and worsening asthma.[11] Bleeding risk is greater among those who are older, drink alcohol, take other NSAIDs, or are on other blood thinners.[11] Aspirin is not recommended in the last part of pregnancy.[11] It is not generally recommended in children with infections because of the risk of Reye syndrome.[11] High doses may result in ringing in the ears.[11]

    precursor to aspirin found in the bark of the willow tree (genus Salix) has been used for its health effects for at least 2,400 years.[12][13] In 1853, chemist Charles Frédéric Gerhardt treated the medicine sodium salicylate with acetyl chloride to produce acetylsalicylic acid for the first time.[14] Over the next 50 years, other chemists, mostly of the German company Bayer, established the chemical structure and devised more efficient production methods.[14]: 69–75  Felix Hoffmann (or Arthur Eichengrün) of Bayer was the first to produce acetylsalicylic acid in a pure, stable form in 1897.[15] By 1899, Bayer had dubbed this drug Aspirin and was selling it globally.[16]: 27 

    Aspirin is available without medical prescription as a proprietary or generic medication[11] in most jurisdictions. It is one of the most widely used medications globally, with an estimated 40,000 tonnes (44,000 tons) (50 to 120 billion pills) consumed each year,[12][17] and is on the World Health Organization’s List of Essential Medicines.[18] In 2022, it was the 36th most commonly prescribed medication in the United States, with more than 16 million prescriptions.[19][20]

    Brand vs. generic name

    [edit]

    In 1897, scientists at the Bayer company began studying acetylsalicylic acid as a less-irritating replacement medication for common salicylate medicines.[14]: 69–75 [21] By 1899, Bayer had named it “Aspirin” and was selling it around the world.[16]

    Aspirin’s popularity grew over the first half of the 20th century, leading to competition between many brands and formulations.[22] The word Aspirin was Bayer’s brand name; however, its rights to the trademark were lost or sold in many countries.[22] The name is ultimately a blend of the prefix a(cetyl) + spir Spiraea, the meadowsweet plant genus from which the acetylsalicylic acid was originally derived at Bayer + -in, the common chemical suffix.[citation needed]

    Chemical properties

    [edit]

    Aspirin decomposes rapidly in solutions of ammonium acetate or the acetatescarbonatescitrates, or hydroxides of the alkali metals. It is stable in dry air, but gradually hydrolyses in contact with moisture to acetic and salicylic acids. In solution with alkalis, the hydrolysis proceeds rapidly and the clear solutions formed may consist entirely of acetate and salicylate.[23]

    Like flour mills, factories producing aspirin tablets must control the amount of the powder that becomes airborne inside the building, because the powder-air mixture can be explosive. The National Institute for Occupational Safety and Health (NIOSH) has set a recommended exposure limit in the United States of 5 mg/m3 (time-weighted average).[24] In 1989, the Occupational Safety and Health Administration (OSHA) set a legal permissible exposure limit for aspirin of 5 mg/m3, but this was vacated by the AFL-CIO v. OSHA decision in 1993.[25]

    Synthesis

    [edit]

    The synthesis of aspirin is classified as an esterification reaction. Salicylic acid is treated with acetic anhydride, an acid derivative, causing a chemical reaction that turns salicylic acid’s hydroxyl group into an ester group (R-OH → R-OCOCH3). This process yields aspirin and acetic acid, which is considered a byproduct of this reaction. Small amounts of sulfuric acid (and occasionally phosphoric acid) are almost always used as a catalyst. This method is commonly demonstrated in undergraduate teaching labs.[26]

    Aspirin synthesis

    Reaction between acetic acid and salicylic acid can also form aspirin but this esterification reaction is reversible and the presence of water can lead to hydrolysis of the aspirin. So, an anhydrous reagent is preferred.[27]Reaction mechanism

    Acetylation of salicylic acid, mechanism

    Formulations containing high concentrations of aspirin often smell like vinegar[28] because aspirin can decompose through hydrolysis in moist conditions, yielding salicylic and acetic acids.[29]

    Physical properties

    [edit]

    Aspirin, an acetyl derivative of salicylic acid, is a white, crystalline, weakly acidic substance that melts at 136 °C (277 °F),[9] and decomposes around 140 °C (284 °F).[30] Its acid dissociation constant (pKa) is 3.5 at 25 °C (77 °F).[31]

    Polymorphism

    [edit]

    Polymorphism, or the ability of a substance to form more than one crystal structure, is important in the development of pharmaceutical ingredients. Many drugs receive regulatory approval for only a single crystal form or polymorph.

    Until 2005, there was only one proven polymorph of aspirin (Form I), though the existence of another polymorph was debated since the 1960s, and one report from 1981 reported that when crystallized in the presence of aspirin anhydride, the diffractogram of aspirin has weak additional peaks. Though at the time it was dismissed as mere impurity, it was, in retrospect, Form II aspirin.[32]

    Form II was reported in 2005,[33][34] found after attempted co-crystallization of aspirin and levetiracetam from hot acetonitrile.

    In form I, pairs of aspirin molecules form centrosymmetric dimers through the acetyl groups with the (acidic) methyl proton to carbonyl hydrogen bonds. In form II, each aspirin molecule forms the same hydrogen bonds, but with two neighbouring molecules instead of one. With respect to the hydrogen bonds formed by the carboxylic acid groups, both polymorphs form identical dimer structures. The aspirin polymorphs contain identical 2-dimensional sections and are therefore more precisely described as polytypes.[35]

    Pure Form II aspirin could be prepared by seeding the batch with aspirin anhydrate in 15% weight.[32]

    Form III was reported in 2015 by compressing form I above 2 GPa, but it reverts back to Form I when pressure is removed.[36] Form IV was reported in 2017. It is stable at ambient conditions.[37]

    Mechanism of action

    [edit]

    Main article: Mechanism of action of aspirin

    Discovery of the mechanism

    [edit]

    In 1971, British pharmacologist John Robert Vane, then employed by the Royal College of Surgeons in London, showed aspirin suppressed the production of prostaglandins and thromboxanes.[38][39] For this discovery he was awarded the 1982 Nobel Prize in Physiology or Medicine, jointly with Sune Bergström and Bengt Ingemar Samuelsson.[40]

    Prostaglandins and thromboxanes

    [edit]

    Aspirin’s ability to suppress the production of prostaglandins and thromboxanes is due to its irreversible inactivation of the cyclooxygenase (COX; officially known as prostaglandin-endoperoxide synthase, PTGS) enzyme required for prostaglandin and thromboxane synthesis. Aspirin acts as an acetylating agent where an acetyl group is covalently attached to a serine residue in the active site of the COX enzyme (Suicide inhibition). This makes aspirin different from other NSAIDs (such as diclofenac and ibuprofen), which are reversible inhibitors.

    Low-dose aspirin use irreversibly blocks the formation of thromboxane A2 in platelets, producing an inhibitory effect on platelet aggregation during the lifetime of the affected platelet (8–9 days). This antithrombotic property makes aspirin useful for reducing the incidence of heart attacks in people who have had a heart attack, unstable angina, ischemic stroke or transient ischemic attack.[41] 40 mg of aspirin a day is able to inhibit a large proportion of maximum thromboxane A2 release provoked acutely, with the prostaglandin I2 synthesis being little affected; however, higher doses of aspirin are required to attain further inhibition.[42]

    Prostaglandins, local hormones produced in the body, have diverse effects, including the transmission of pain information to the brain, modulation of the hypothalamic thermostat, and inflammation. Thromboxanes are responsible for the aggregation of platelets that form blood clots. Heart attacks are caused primarily by blood clots, and low doses of aspirin are seen as an effective medical intervention to prevent a second acute myocardial infarction.[43]

    COX-1 and COX-2 inhibition

    [edit]

    At least two different types of cyclooxygenasesCOX-1 and COX-2, are acted on by aspirin. Aspirin irreversibly inhibits COX-1 and modifies the enzymatic activity of COX-2. COX-2 normally produces prostanoids, most of which are proinflammatory. Aspirin-modified COX-2 (aka prostaglandin-endoperoxide synthase 2 or PTGS2) produces epi-lipoxins, most of which are anti-inflammatory.[44][verification needed][45] Newer NSAID drugs, COX-2 inhibitors (coxibs), have been developed to inhibit only COX-2, with the intent to reduce the incidence of gastrointestinal side effects.[17]

    Several COX-2 inhibitors, such as rofecoxib (Vioxx), have been withdrawn from the market, after evidence emerged that COX-2 inhibitors increase the risk of heart attack and stroke.[46][47] Endothelial cells lining the microvasculature in the body are proposed to express COX-2, and, by selectively inhibiting COX-2, prostaglandin production (specifically, PGI2; prostacyclin) is downregulated with respect to thromboxane levels, as COX-1 in platelets is unaffected. Thus, the protective anticoagulative effect of PGI2 is removed, increasing the risk of thrombus and associated heart attacks and other circulatory problems. Since platelets have no DNA, they are unable to synthesize new COX-1 once aspirin has irreversibly inhibited the enzyme, an important difference as compared with reversible inhibitors.

    Furthermore, aspirin, while inhibiting the ability of COX-2 to form pro-inflammatory products such as the prostaglandins, converts this enzyme’s activity from a prostaglandin-forming cyclooxygenase to a lipoxygenase-like enzyme: aspirin-treated COX-2 metabolizes a variety of polyunsaturated fatty acids to hydroperoxy products which are then further metabolized to specialized proresolving mediators such as the aspirin-triggered lipoxins(15-epilipoxin-A4/B4), aspirin-triggered resolvins, and aspirin-triggered maresins. These mediators possess potent anti-inflammatory activity. It is proposed that this aspirin-triggered transition of COX-2 from cyclooxygenase to lipoxygenase activity and the consequential formation of specialized proresolving mediators contributes to the anti-inflammatory effects of aspirin.[48][49][50]

    Additional mechanisms

    [edit]

    Aspirin has been shown to have at least three additional modes of action. It uncouples oxidative phosphorylation in cartilaginous (and hepatic) mitochondria, by diffusing from the inner membrane space as a proton carrier back into the mitochondrial matrix, where it ionizes once again to release protons.[51] Aspirin buffers and transports the protons. When high doses are given, it may actually cause fever, owing to the heat released from the electron transport chain, as opposed to the antipyretic action of aspirin seen with lower doses. In addition, aspirin induces the formation of NO-radicals in the body, which have been shown in mice to have an independent mechanism of reducing inflammation. This reduced leukocyte adhesion is an important step in the immune response to infection; however, evidence is insufficient to show aspirin helps to fight infection.[52] More recent data also suggest salicylic acid and its derivatives modulate signalling through NF-κB.[53] NF-κB, a transcription factor complex, plays a central role in many biological processes, including inflammation.[54][55][56]

    Aspirin is readily broken down in the body to salicylic acid, which itself has anti-inflammatory, antipyretic, and analgesic effects. In 2012, salicylic acid was found to activate AMP-activated protein kinase, which has been suggested as a possible explanation for some of the effects of both salicylic acid and aspirin.[57][58] The acetyl portion of the aspirin molecule has its own targets. Acetylation of cellular proteins is a well-established phenomenon in the regulation of protein function at the post-translational level. Aspirin is able to acetylate several other targets in addition to COX isoenzymes.[59][60] These acetylation reactions may explain many hitherto unexplained effects of aspirin.[61]

    Formulations

    [edit]

    This section needs expansion. You can help by adding to it(January 2023)

    Aspirin is produced in many formulations, with some differences in effect. In particular, aspirin can cause gastrointestinal bleeding, and formulations are sought which deliver the benefits of aspirin while mitigating harmful bleeding. Formulations may be combined (e.g., buffered + vitamin C).

    • Tablets, typically of about 75–100 mg and 300–320 mg of immediate-release aspirin (IR-ASA).
    • Dispersible tablets.
    • Enteric-coated tablets.
    • Buffered formulations containing aspirin with one of many buffering agents.
    • Formulations of aspirin with vitamin C (ASA-VitC)
    • A phospholipid-aspirin complex liquid formulation, PL-ASA. As of 2023 the phospholipid coating was being trialled to determine if it caused less gastrointestinal damage.[62]

    Pharmacokinetics

    [edit]

    Acetylsalicylic acid is a weak acid, and very little of it is ionized in the stomach after oral administration. Acetylsalicylic acid is quickly absorbed through the cell membrane in the acidic conditions of the stomach. The increased pH and larger surface area of the small intestine causes aspirin to be absorbed more slowly there, as more of it is ionized. Owing to the formation of concretions, aspirin is absorbed much more slowly during overdose, and plasma concentrations can continue to rise for up to 24 hours after ingestion.[63][64][65]

    About 50–80% of salicylate in the blood is bound to human serum albumin, while the rest remains in the active, ionized state; protein binding is concentration-dependent. Saturation of binding sites leads to more free salicylate and increased toxicity. The volume of distribution is 0.1–0.2 L/kg. Acidosis increases the volume of distribution because of enhancement of tissue penetration of salicylates.[65]

    As much as 80% of therapeutic doses of salicylic acid is metabolized in the liverConjugation with glycine forms salicyluric acid, and with glucuronic acid to form two different glucuronide esters. The conjugate with the acetyl group intact is referred to as the acyl glucuronide; the deacetylated conjugate is the phenolic glucuronide. These metabolic pathways have only a limited capacity. Small amounts of salicylic acid are also hydroxylated to gentisic acid. With large salicylate doses, the kinetics switch from first-order to zero-order, as metabolic pathways become saturated and renal excretion becomes increasingly important.[65]

    Salicylates are excreted mainly by the kidneys as salicyluric acid (75%), free salicylic acid (10%), salicylic phenol (10%), and acyl glucuronides (5%), gentisic acid (< 1%), and 2,3-dihydroxybenzoic acid.[66] When small doses (less than 250 mg in an adult) are ingested, all pathways proceed by first-order kinetics, with an elimination half-life of about 2.0 h to 4.5 h.[67][68] When higher doses of salicylate are ingested (more than 4 g), the half-life becomes much longer (15 h to 30 h),[69] because the biotransformation pathways concerned with the formation of salicyluric acid and salicyl phenolic glucuronide become saturated.[70] Renal excretion of salicylic acid becomes increasingly important as the metabolic pathways become saturated, because it is extremely sensitive to changes in urinary pH. A 10- to 20-fold increase in renal clearance occurs when urine pH is increased from 5 to 8. The use of urinary alkalinization exploits this particular aspect of salicylate elimination.[71] It was found that short-term aspirin use in therapeutic doses might precipitate reversible acute kidney injury when the patient was ill with glomerulonephritis or cirrhosis.[72] Aspirin for some patients with chronic kidney disease and some children with congestive heart failure was contraindicated.[72]

    History

    [edit]

    Main article: History of aspirin

    1923 advertisement

    Medicines made from willow and other salicylate-rich plants appear in clay tablets from ancient Sumer as well as the Ebers Papyrus from ancient Egypt.[14]: 8–13 [22] Hippocrates referred to the use of salicylic tea to reduce fevers around 400 BC, and willow bark preparations were part of the pharmacopoeia of Western medicine in classical antiquity and the Middle Ages.[22] Willow bark extract became recognized for its specific effects on fever, pain, and inflammation in the mid-eighteenth century[73] after the Rev Edward Stone of Chipping Norton, Oxfordshire, noticed that the bitter taste of willow bark resembled the taste of the bark of the cinchona tree, known as “Peruvian bark“, which was used successfully in Peru to treat a variety of ailments. Stone experimented with preparations of powdered willow bark on people in Chipping Norton for five years and found it to be as effective as Peruvian bark and a cheaper domestic version. In 1763 he sent a report of his findings to the Royal Society in London.[74] By the nineteenth century, pharmacists were experimenting with and prescribing a variety of chemicals related to salicylic acid, the active component of willow extract.[14]: 46–55 

    Old package. “Export from Germany is prohibited”

    In 1853, chemist Charles Frédéric Gerhardt treated sodium salicylate with acetyl chloride to produce acetylsalicylic acid for the first time;[14]: 46–48  in the second half of the 19th century, other academic chemists established the compound’s chemical structure and devised more efficient methods of synthesis. In 1897, scientists at the drug and dye firm Bayer began investigating acetylsalicylic acid as a less-irritating replacement for standard common salicylate medicines, and identified a new way to synthesize it.[14]: 69–75  That year, Felix Hoffmann (or Arthur Eichengrün) of Bayer was the first to produce acetylsalicylic acid in a pure, stable form.[15]

    Salicylic acid had been extracted in 1838 from the herb meadowsweet, whose German name, Spirsäure, was the basis for naming the newly synthesized drug, which, by 1899, Bayer was selling globally.[14]: 46–55 [16]: 27  The word Aspirin was Bayer’s brand name, rather than the generic name of the drug; however, Bayer’s rights to the trademark were lost or sold in many countries. Aspirin’s popularity grew over the first half of the 20th century, leading to fierce competition with the proliferation of aspirin brands and products.[22]

    Aspirin’s popularity declined after the development of acetaminophen/paracetamol in 1956 and ibuprofen in 1962. In the 1960s and 1970s, John Vane and others discovered the basic mechanism of aspirin’s effects,[14]: 226–231  while clinical trials and other studies from the 1960s to the 1980s established aspirin’s efficacy as an anti-clotting agent that reduces the risk of clotting diseases.[14]: 247–257  The initial large studies on the use of low-dose aspirin to prevent heart attacks that were published in the 1970s and 1980s helped spur reform in clinical research ethics and guidelines for human subject research and US federal law, and are often cited as examples of clinical trials that included only men, but from which people drew general conclusions that did not hold true for women.[75][76][77]

    Aspirin sales revived considerably in the last decades of the 20th century, and remain strong in the 21st century with widespread use as a preventive treatment for heart attacks and strokes.[14]: 267–269 

    Trademark

    [edit]

    Four boxes of medication on a store shelf above price tags. The two on the left are yellow with "Aspirin" in bold black type and explanatory text in English on the top box and French on the bottom. The two on the right are slightly smaller and white with the word "Life" in the corner inside a red circle. The text, in French on top and English below, describes the medication as "acetylsalicylic acid tablets"

    In Canada and many other countries, “Aspirin” remains a trademark, so generic aspirin is sold as “ASA” (acetylsalicylic acid).

    Four plastic bottles of medication on another drugstore shelf above their price tags. The two on the left are yellow with the word "Bayer" prominent in black type; above small type describes the product as "genuine aspirin". On the left are two clear plastic bottles with the Rite Aid drugstore chain logo on their yellow labels, which describe the product as "pain relief aspirin".

    In the US., “aspirin” is a generic name.

    Bayer lost its trademark for Aspirin in the United States and some other countries in actions taken between 1918 and 1921 because it had failed to use the name for its own product correctly and had for years allowed the use of “Aspirin” by other manufacturers without defending the intellectual property rights.[78] Today, aspirin is a generic trademark in many countries.[79][80] Aspirin, with a capital “A”, remains a registered trademark of Bayer in Germany, Canada, Mexico, and in over 80 other countries, for acetylsalicylic acid in all markets, but using different packaging and physical aspects for each.[81][82]

    Compendial status

    [edit]

    Medical use

    [edit]

    Aspirin is used in the treatment of a number of conditions, including fever, pain, rheumatic fever, and inflammatory conditions, such as rheumatoid arthritispericarditis, and Kawasaki disease.[11] Lower doses of aspirin have also been shown to reduce the risk of death from a heart attack, or the risk of stroke in people who are at high risk or who have cardiovascular disease, but not in elderly people who are otherwise healthy.[85][86][87][88][89] There is evidence that aspirin is effective at preventing colorectal cancer, though the mechanisms of this effect are unclear.[90]

    Pain

    [edit]

    Aspirin is an effective analgesic for acute pain, although it is generally considered inferior to ibuprofen because aspirin is more likely to cause gastrointestinal bleeding.[91] Aspirin is generally ineffective for those pains caused by muscle crampsbloatinggastric distension, or acute skin irritation.[92] As with other NSAIDs, combinations of aspirin and caffeine provide slightly greater pain relief than aspirin alone.[93] Effervescent formulations of aspirin relieve pain faster than aspirin in tablets,[94] which makes them useful for the treatment of migraines.[95] Topical aspirin may be effective for treating some types of neuropathic pain.[96]

    Aspirin, either by itself or in a combined formulation, effectively treats certain types of a headache, but its efficacy may be questionable for others. Secondary headaches, meaning those caused by another disorder or trauma, should be promptly treated by a medical provider. Among primary headaches, the International Classification of Headache Disorders distinguishes between tension headache (the most common), migraine, and cluster headache. Aspirin or other over-the-counter analgesics are widely recognized as effective for the treatment of tension headaches.[97] Aspirin, especially as a component of an aspirin/paracetamol/caffeine combination, is considered a first-line therapy in the treatment of migraine, and comparable to lower doses of sumatriptan. It is most effective at stopping migraines when they are first beginning.[98]

    Fever

    [edit]

    Like its ability to control pain, aspirin’s ability to control fever is due to its action on the prostaglandin system through its irreversible inhibition of COX.[99] Although aspirin’s use as an antipyretic in adults is well established, many medical societies and regulatory agencies, including the American Academy of Family Physicians, the American Academy of Pediatrics, and the Food and Drug Administration, strongly advise against using aspirin for the treatment of fever in children because of the risk of Reye’s syndrome, a rare but often fatal illness associated with the use of aspirin or other salicylates in children during episodes of viral or bacterial infection.[100][101][102] Because of the risk of Reye’s syndrome in children, in 1986, the US Food and Drug Administration (FDA) required labeling on all aspirin-containing medications advising against its use in children and teenagers.[103]

    Inflammation

    [edit]

    Aspirin is used as an anti-inflammatory agent for both acute and long-term inflammation,[104] as well as for the treatment of inflammatory diseases, such as rheumatoid arthritis.[11]

    Heart attacks and strokes

    [edit]

    Aspirin is an important part of the treatment of those who have had a heart attack.[105] It is generally not recommended for routine use by people with no other health problems, including those over the age of 70.[106]

    The 2009 Antithrombotic Trialists’ Collaboration published in Lancet evaluated the efficacy and safety of low dose aspirin in secondary prevention. In those with prior ischaemic stroke or acute myocardial infarction, daily low dose aspirin was associated with a 19% relative risk reduction of serious cardiovascular events (non-fatal myocardial infarction, non-fatal stroke, or vascular death). This did come at the expense of a 0.19% absolute risk increase in gastrointestinal bleeding; however, the benefits outweigh the hazard risk in this case.[citation needed] Data from previous trials have suggested that weight-based dosing of aspirin has greater benefits in primary prevention of cardiovascular outcomes.[107] However, more recent trials were not able to replicate similar outcomes using low dose aspirin in low body weight (<70 kg) in specific subset of population studied i.e. elderly and diabetic population, and more evidence is required to study the effect of high dose aspirin in high body weight (≥70 kg).[108][109][110]

    After percutaneous coronary interventions (PCIs), such as the placement of a coronary artery stent, a U.S. Agency for Healthcare Research and Quality guideline recommends that aspirin be taken indefinitely.[111] Frequently, aspirin is combined with an ADP receptor inhibitor, such as clopidogrelprasugrel, or ticagrelor to prevent blood clots. This is called dual antiplatelet therapy (DAPT). Duration of DAPT was advised in the United States and European Union guidelines after the CURE[112] and PRODIGY[113] studies. In 2020, the systematic review and network meta-analysis from Khan et al.[114] showed promising benefits of short-term (< 6 months) DAPT followed by P2Y12 inhibitors in selected patients, as well as the benefits of extended-term (> 12 months) DAPT in high risk patients. In conclusion, the optimal duration of DAPT after PCIs should be personalized after outweighing each patient’s risks of ischemic events and risks of bleeding events with consideration of multiple patient-related and procedure-related factors. Moreover, aspirin should be continued indefinitely after DAPT is complete.[115][116][117]

    The status of the use of aspirin for the primary prevention in cardiovascular disease is conflicting and inconsistent, with recent changes from previously recommending it widely decades ago, and that some referenced newer trials in clinical guidelines show less of benefit of adding aspirin alongside other anti-hypertensive and cholesterol lowering therapies.[106][118] The ASCEND study demonstrated that in high-bleeding risk diabetics with no prior cardiovascular disease, there is no overall clinical benefit (12% decrease in risk of ischaemic events v/s 29% increase in GI bleeding) of low dose aspirin in preventing the serious vascular events over a period of 7.4 years. Similarly, the results of the ARRIVE study also showed no benefit of same dose of aspirin in reducing the time to first cardiovascular outcome in patients with moderate risk of cardiovascular disease over a period of five years. Aspirin has also been suggested as a component of a polypill for prevention of cardiovascular disease.[119][120] Complicating the use of aspirin for prevention is the phenomenon of aspirin resistance.[121][122] For people who are resistant, aspirin’s efficacy is reduced.[123] Some authors have suggested testing regimens to identify people who are resistant to aspirin.[124]

    As of April 2022, the United States Preventive Services Task Force (USPSTF) determined that there was a “small net benefit” for patients aged 40–59 with a 10% or greater 10-year cardiovascular disease (CVD) risk, and “no net benefit” for patients aged over 60.[125][126][127] Determining the net benefit was based on balancing the risk reduction of taking aspirin for heart attacks and ischaemic strokes, with the increased risk of gastrointestinal bleedingintracranial bleeding, and hemorrhagic strokes. Their recommendations state that age changes the risk of the medicine, with the magnitude of the benefit of aspirin coming from starting at a younger age, while the risk of bleeding, while small, increases with age, particular for adults over 60, and can be compounded by other risk factors such as diabetes and a history of gastrointestinal bleeding. As a result, the USPSTF suggests that “people ages 40 to 59 who are at higher risk for CVD should decide with their clinician whether to start taking aspirin; people 60 or older should not start taking aspirin to prevent a first heart attack or stroke.” Primary prevention guidelines from September 2019 made by the American College of Cardiology and the American Heart Association state they might consider aspirin for patients aged 40–69 with a higher risk of atherosclerotic CVD, without an increased bleeding risk, while stating they would not recommend aspirin for patients aged over 70 or adults of any age with an increased bleeding risk.[106] They state a CVD risk estimation and a risk discussion should be done before starting on aspirin, while stating aspirin should be used “infrequently in the routine primary prevention of (atherosclerotic CVD) because of lack of net benefit”. As of August 2021, the European Society of Cardiology made similar recommendations; considering aspirin specifically to patients aged less than 70 at high or very high CVD risk, without any clear contraindications, on a case-by-case basis considering both ischemic risk and bleeding risk.[118]

    Cancer prevention

    [edit]

    Aspirin may reduce the overall risk of both getting cancer and dying from cancer.[128] There is substantial evidence for lowering the risk of colorectal cancer (CRC),[90][129][130][131] but aspirin must be taken for at least 10–20 years to see this benefit.[132] It may also slightly reduce the risk of endometrial cancer[133] and prostate cancer.[134]

    Some conclude the benefits are greater than the risks due to bleeding in those at average risk.[128] Others are unclear if the benefits are greater than the risk.[135][136] Given this uncertainty, the 2007 United States Preventive Services Task Force (USPSTF) guidelines on this topic recommended against the use of aspirin for prevention of CRC in people with average risk.[137] Nine years later however, the USPSTF issued a grade B recommendation for the use of low-dose aspirin (75 to 100 mg/day) “for the primary prevention of CVD [cardiovascular disease] and CRC in adults 50 to 59 years of age who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years”.[138]

    A meta-analysis through 2019 said that there was an association between taking aspirin and lower risk of cancer of the colorectum, esophagus, and stomach.[139]

    In 2021, the U.S. Preventive services Task Force raised questions about the use of aspirin in cancer prevention. It notes the results of the 2018 ASPREE (Aspirin in Reducing Events in the Elderly) Trial, in which the risk of cancer-related death was higher in the aspirin-treated group than in the placebo group.[140]

    In 2025, a group of scientists at the University of Cambridge found that aspirin stimulates the immune system to reduce cancer metastasis. They found that a protein called ARHGEF1 suppresses T cells, that are required for attacking metastatic cancer cells. Aspirin appeared to counteract this suppression by targeting a clotting factor called thromboxane A2 (TXA2), which activates ARHGEF1, thus preventing it from suppressing the T cells.[141] The researchers called the discovery a “Eureka moment”.[142] It was reported that the findings could lead to a more targeted use for aspirin in cancer research.[143] It was also said that taking self-medicating with aspirin should not be done yet due to its potential side effects until clinical trials were held.[144]

    Psychiatry

    [edit]

    Bipolar disorder

    [edit]

    Aspirin, along with several other agents with anti-inflammatory properties, has been repurposed as an add-on treatment for depressive episodes in subjects with bipolar disorder in light of the possible role of inflammation in the pathogenesis of severe mental disorders.[145] A 2022 systematic review concluded that aspirin exposure reduced the risk of depression in a pooled cohort of three studies (HR 0.624, 95% CI: 0.0503, 1.198, P=0.033). However, further high-quality, longer-duration, double-blind randomized controlled trials (RCTs) are needed to determine whether aspirin is an effective add-on treatment for bipolar depression.[146][147][148] Thus, notwithstanding the biological rationale, the clinical perspectives of aspirin and anti-inflammatory agents in the treatment of bipolar depression remain uncertain.[145]

    Dementia

    [edit]

    Although cohort and longitudinal studies have shown low-dose aspirin has a greater likelihood of reducing the incidence of dementia, numerous randomized controlled trials have not validated this.[149][150]

    Schizophrenia

    [edit]

    Some researchers have speculated the anti-inflammatory effects of aspirin may be beneficial for schizophrenia. Small trials have been conducted but evidence remains lacking.[151][152]

    Other uses

    [edit]

    Aspirin is a first-line treatment for the fever and joint-pain symptoms of acute rheumatic fever. The therapy often lasts for one to two weeks, and is rarely indicated for longer periods. After fever and pain have subsided, the aspirin is no longer necessary, since it does not decrease the incidence of heart complications and residual rheumatic heart disease.[153][154] Naproxen has been shown to be as effective as aspirin and less toxic, but due to the limited clinical experience, naproxen is recommended only as a second-line treatment.[153][155]

    Along with rheumatic fever, Kawasaki disease remains one of the few indications for aspirin use in children[156] in spite of a lack of high quality evidence for its effectiveness.[157]

    Low-dose aspirin supplementation has moderate benefits when used for prevention of pre-eclampsia.[158][159] This benefit is greater when started in early pregnancy.[160]

    Aspirin has also demonstrated anti-tumoral effects, via inhibition of the PTTG1 gene, which is often overexpressed in tumors.[161]

    Resistance

    [edit]

    See also: Drug tolerance

    For some people, aspirin does not have as strong an effect on platelets as for others, an effect known as aspirin-resistance or insensitivity. One study has suggested women are more likely to be resistant than men,[162] and a different, aggregate study of 2,930 people found 28% were resistant.[163] A study in 100 Italian people found, of the apparent 31% aspirin-resistant subjects, only 5% were truly resistant, and the others were noncompliant.[164] Another study of 400 healthy volunteers found no subjects who were truly resistant, but some had “pseudoresistance, reflecting delayed and reduced drug absorption”. [165]

    Meta-analysis and systematic reviews have concluded that laboratory confirmed aspirin resistance confers increased rates of poorer outcomes in cardiovascular and neurovascular diseases.[166][163][167][168][169][170] Although the majority of research conducted has surrounded cardiovascular and neurovascular, there is emerging research into the risk of aspirin resistance after orthopaedic surgery where aspirin is used for venous thromboembolism prophylaxis.[171] Aspirin resistance in orthopaedic surgery, specifically after total hip and knee arthroplasties, is of interest as risk factors for aspirin resistance are also risk factors for venous thromboembolisms and osteoarthritis; the sequelae of requiring a total hip or knee arthroplasty. Some of these risk factors include obesity, advancing age, diabetes mellitus, dyslipidemia and inflammatory diseases.[171]

    Dosages

    [edit]

    Adult aspirin tablets are produced in standardised sizes, which vary slightly from country to country, for example 300 mg in Britain and 325 mg in the United States. Smaller doses are based on these standards, e.g., 75 mg and 81 mg tablets. The 81 mg tablets are commonly called “baby aspirin” or “baby-strength”, because they were originally – but no longer – intended to be administered to infants and children.[172] No medical significance occurs due to the slight difference in dosage between the 75 mg and the 81 mg tablets. The dose required for benefit appears to depend on a person’s weight.[107] For those weighing less than 70 kilograms (154 lb), low dose is effective for preventing cardiovascular disease; for patients above this weight, higher doses are required.[107]

    In general, for adults, doses are taken four times a day for fever or arthritis,[173] with doses near the maximal daily dose used historically for the treatment of rheumatic fever.[174] For the prevention of myocardial infarction (MI) in someone with documented or suspected coronary artery disease, much lower doses are taken once daily.[173]

    March 2009 recommendations from the USPSTF on the use of aspirin for the primary prevention of coronary heart disease encourage men aged 45–79 and women aged 55–79 to use aspirin when the potential benefit of a reduction in MI for men or stroke for women outweighs the potential harm of an increase in gastrointestinal hemorrhage.[175][176][needs update] The WHI study of postmenopausal women found that aspirin resulted in a 25% lower risk of death from cardiovascular disease and a 14% lower risk of death from any cause, though there was no significant difference between 81 mg and 325 mg aspirin doses.[177] The 2021 ADAPTABLE study also showed no significant difference in cardiovascular events or major bleeding between 81 mg and 325 mg doses of aspirin in patients (both men and women) with established cardiovascular disease.[178]

    Low-dose aspirin use was also associated with a trend toward lower risk of cardiovascular events, and lower aspirin doses (75 or 81 mg/day) may optimize efficacy and safety for people requiring aspirin for long-term prevention.[176]

    In children with Kawasaki disease, aspirin is taken at dosages based on body weight, initially four times a day for up to two weeks and then at a lower dose once daily for a further six to eight weeks.[179]

    Adverse effects

    [edit]

    In October 2020, the US Food and Drug Administration (FDA) required the drug label to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in unborn babies that result in low amniotic fluid.[180][181] They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.[180][181] One exception to the recommendation is the use of low-dose 81 mg aspirin at any point in pregnancy under the direction of a health care professional.[181]

    Contraindications

    [edit]

    Aspirin should not be taken by people who are allergic to ibuprofen or naproxen,[182][183] or who have salicylate intolerance[184][185] or a more generalized drug intolerance to NSAIDs, and caution should be exercised in those with asthma or NSAID-precipitated bronchospasm. Owing to its effect on the stomach lining, manufacturers recommend people with peptic ulcers, mild diabetes, or gastritis seek medical advice before using aspirin.[182][186] Even if none of these conditions is present, the risk of stomach bleeding is still increased when aspirin is taken with alcohol or warfarin.[182][183] People with hemophilia or other bleeding tendencies should not take aspirin or other salicylates.[182][186] Aspirin is known to cause hemolytic anemia in people who have the genetic disease glucose-6-phosphate dehydrogenase deficiency, particularly in large doses and depending on the severity of the disease.[187] Use of aspirin during dengue fever is not recommended owing to increased bleeding tendency.[188] Aspirin taken at doses of ≤325 mg and ≤100 mg per day for ≥2 days can increase the odds of suffering a gout attack by 81% and 91% respectively. This effect may potentially be worsened by high purine diets, diuretics, and kidney disease, but is eliminated by the urate lowering drug allopurinol.[189] Daily low dose aspirin does not appear to worsen kidney function.[190] Aspirin may reduce cardiovascular risk in those without established cardiovascular disease in people with moderate CKD, without significantly increasing the risk of bleeding.[191] Aspirin should not be given to children or adolescents under the age of 16 to control cold or influenza symptoms, as this has been linked with Reye’s syndrome.[192]

    Gastrointestinal

    [edit]

    Aspirin increases the risk of upper gastrointestinal bleeding.[193] Enteric coating on aspirin may be used in manufacturing to prevent release of aspirin into the stomach to reduce gastric harm, but enteric coating does not reduce gastrointestinal bleeding risk.[193][194] Enteric-coated aspirin may not be as effective at reducing blood clot risk.[195][196] Combining aspirin with other NSAIDs has been shown to further increase the risk of gastrointestinal bleeding.[193] Using aspirin in combination with clopidogrel or warfarin also increases the risk of upper gastrointestinal bleeding.[197]

    Blockade of COX-1 by aspirin apparently results in the upregulation of COX-2 as part of a gastric defense.[198] There is no clear evidence that simultaneous use of a COX-2 inhibitor with aspirin may increase the risk of gastrointestinal injury.[199]

    Buffering” is an additional method used with the intent to mitigate gastrointestinal bleeding, such as by preventing aspirin from concentrating in the walls of the stomach, although the benefits of buffered aspirin are disputed.[200] Almost any buffering agent used in antacids can be used; Bufferin, for example, uses magnesium oxide. Other preparations use calcium carbonate.[201] Gas-forming agents in effervescent tablet and powder formulations can also double as a buffering agent, one example being sodium bicarbonate, used in Alka-Seltzer.[202]

    Taking vitamin C with aspirin has been investigated as a method of protecting the stomach lining. In trials vitamin C-releasing aspirin (ASA-VitC) or a buffered aspirin formulation containing vitamin C was found to cause less stomach damage than aspirin alone.[203][204]

    Retinal vein occlusion

    [edit]

    It is a widespread habit among eye specialists (ophthalmologists) to prescribe aspirin as an add-on medication for patients with retinal vein occlusion (RVO), such as central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). The reason of this widespread use is the evidence of its proven effectiveness in major systemic venous thrombotic disorders, and it has been assumed that may be similarly beneficial in various types of retinal vein occlusion.

    However, a large-scale investigation based on data of nearly 700 patients showed “that aspirin or other antiplatelet aggregating agents or anticoagulants adversely influence the visual outcome in patients with CRVO and hemi-CRVO, without any evidence of protective or beneficial effect”.[205] Several expert groups, including the Royal College of Ophthalmologists, recommended against the use of antithrombotic drugs (incl. aspirin) for patients with RVO.[206]

    Central effects

    [edit]

    Large doses of salicylate, a metabolite of aspirin, cause temporary tinnitus (ringing in the ears) based on experiments in rats, via the action on arachidonic acid and NMDA receptors cascade.[207]

    Reye’s syndrome

    [edit]

    Main article: Reye’s syndrome

    Reye’s syndrome, a rare but severe illness characterized by acute encephalopathy and fatty liver, can occur when children or adolescents are given aspirin for a fever or other illness or infection. From 1981 to 1997, 1207 cases of Reye’s syndrome in people younger than 18 were reported to the US Centers for Disease Control and Prevention (CDC). Of these, 93% reported being ill in the three weeks preceding the onset of Reye’s syndrome, most commonly with a respiratory infectionchickenpox, or diarrhea. Salicylates were detectable in 81.9% of children for whom test results were reported.[208] After the association between Reye’s syndrome and aspirin was reported, and safety measures to prevent it (including a Surgeon General‘s warning, and changes to the labeling of aspirin-containing drugs) were implemented, aspirin taken by children declined considerably in the United States, as did the number of reported cases of Reye’s syndrome; a similar decline was found in the United Kingdom after warnings against pediatric aspirin use were issued.[208] The US Food and Drug Administration recommends aspirin (or aspirin-containing products) should not be given to anyone under the age of 12 who has a fever,[192] and the UK National Health Service recommends children who are under 16 years of age should not take aspirin, unless it is on the advice of a doctor.[209]

    Skin

    [edit]

    For a small number of people, taking aspirin can result in symptoms including hives, swelling, and headache.[210] Aspirin can exacerbate symptoms among those with chronic hives, or create acute symptoms of hives.[211] These responses can be due to allergic reactions to aspirin, or more often due to its effect of inhibiting the COX-1 enzyme.[211][212] Skin reactions may also tie to systemic contraindications, seen with NSAID-precipitated bronchospasm,[211][212] or those with atopy.[213]

    Aspirin and other NSAIDs, such as ibuprofen, may delay the healing of skin wounds.[214] Earlier findings from two small, low-quality trials suggested a benefit with aspirin (alongside compression therapy) on venous leg ulcer healing time and leg ulcer size,[215][216][217] however larger, more recent studies of higher quality have been unable to corroborate these outcomes.[218][219] As such, further research is required to clarify the role of aspirin in this context.

    Other adverse effects

    [edit]

    Aspirin can induce swelling of skin tissues in some people. In one study, angioedema appeared one to six hours after ingesting aspirin in some of the people. However, when the aspirin was taken alone, it did not cause angioedema in these people; the aspirin had been taken in combination with another NSAID-induced drug when angioedema appeared.[220]

    Aspirin causes an increased risk of cerebral microbleeds, having the appearance on MRI scans of 5 to 10 mm or smaller, hypointense (dark holes) patches.[221][222]

    A study of a group with a mean dosage of aspirin of 270 mg per day estimated an average absolute risk increase in intracerebral hemorrhage (ICH) of 12 events per 10,000 persons.[223] In comparison, the estimated absolute risk reduction in myocardial infarction was 137 events per 10,000 persons, and a reduction of 39 events per 10,000 persons in ischemic stroke.[223] In cases where ICH already has occurred, aspirin use results in higher mortality, with a dose of about 250 mg per day resulting in a relative risk of death within three months after the ICH around 2.5 (95% confidence interval 1.3 to 4.6).[224]

    Aspirin and other NSAIDs can cause abnormally high blood levels of potassium by inducing a hyporeninemic hypoaldosteronism state via inhibition of prostaglandin synthesis; however, these agents do not typically cause hyperkalemia by themselves in the setting of normal renal function and euvolemic state.[225]

    Use of low-dose aspirin before a surgical procedure has been associated with an increased risk of bleeding events in some patients, however, ceasing aspirin prior to surgery has also been associated with an increase in major adverse cardiac events. An analysis of multiple studies found a three-fold increase in adverse events such as myocardial infarction in patients who ceased aspirin prior to surgery. The analysis found that the risk is dependent on the type of surgery being performed and the patient indication for aspirin use.[226]

    On 9 July 2015, the US Food and Drug Administration (FDA) toughened warnings of increased heart attack and stroke risk associated with nonsteroidal anti-inflammatory drugs (NSAID).[227] Aspirin is an NSAID but is not affected by the new warnings.[227]

    Overdose

    [edit]

    Main article: Aspirin poisoning

    Aspirin overdose can be acute or chronic. In acute poisoning, a single large dose is taken; in chronic poisoning, higher than normal doses are taken over a period of time. Acute overdose has a mortality rate of 2%. Chronic overdose is more commonly lethal, with a mortality rate of 25%;[228] chronic overdose may be especially severe in children.[229] Toxicity is managed with a number of potential treatments, including activated charcoal, intravenous dextrose and normal saline, sodium bicarbonate, and dialysis.[230] The diagnosis of poisoning usually involves measurement of plasma salicylate, the active metabolite of aspirin, by automated spectrophotometric methods. Plasma salicylate levels in general range from 30 to 100 mg/L after usual therapeutic doses, 50–300 mg/L in people taking high doses and 700–1400 mg/L following acute overdose. Salicylate is also produced as a result of exposure to bismuth subsalicylatemethyl salicylate, and sodium salicylate.[231][232]

    Interactions

    [edit]

    Aspirin is known to interact with other drugs. For example, acetazolamide and ammonium chloride are known to enhance the intoxicating effect of salicylates, and alcohol also increases the gastrointestinal bleeding associated with these types of drugs.[182][183] Aspirin is known to displace a number of drugs from protein-binding sites in the blood, including the antidiabetic drugs tolbutamide and chlorpropamidewarfarinmethotrexatephenytoinprobenecidvalproic acid (as well as interfering with beta oxidation, an important part of valproate metabolism), and other NSAIDs. Corticosteroids may also reduce the concentration of aspirin. Other NSAIDs, such as ibuprofen and naproxen, may reduce the antiplatelet effect of aspirin.[233][234] Although limited evidence suggests this may not result in a reduced cardioprotective effect of aspirin.[233] Analgesic doses of aspirin decrease sodium loss induced by spironolactone in the urine, however this does not reduce the antihypertensive effects of spironolactone.[235] Furthermore, antiplatelet doses of aspirin are deemed too small to produce an interaction with spironolactone.[236] Aspirin is known to compete with penicillin G for renal tubular secretion.[237] Aspirin may also inhibit the absorption of vitamin C.[238][239][unreliable medical source?][240]

    Research

    [edit]

    The ISIS-2 trial demonstrated that aspirin at doses of 160 mg daily for one month, decreased the mortality by 21% of participants with a suspected myocardial infarction in the first five weeks.[241] A single daily dose of 324 mg of aspirin for 12 weeks has a highly protective effect against acute myocardial infarction and death in men with unstable angina.[242]

    Bipolar disorder

    [edit]

    Aspirin has been repurposed as an add-on treatment for depressive episodes in subjects with bipolar disorder.[145] However, meta-analytic evidence is based on very few studies and does not suggest any efficacy of aspirin in the treatment of bipolar depression.[145] Thus, notwithstanding the biological rationale, the clinical perspectives of aspirin and anti-inflammatory agents in the treatment of bipolar depression remain uncertain.[145]

    Infectious diseases

    [edit]

    Several studies investigated the anti-infective properties of aspirin for bacterial, viral and parasitic infections. Aspirin was demonstrated to limit platelet activation induced by Staphylococcus aureus and Enterococcus faecalis and to reduce streptococcal adhesion to heart valves. In patients with tuberculous meningitis, the addition of aspirin reduced the risk of new cerebral infarction [RR = 0.52 (0.29-0.92)]. A role of aspirin on bacterial and fungal biofilm is also being supported by growing evidence.[243]

    Cancer prevention

    [edit]

    Evidence from observational studies was conflicting on the effect of aspirin in breast cancer prevention;[244] a randomized controlled trial showed that aspirin had no significant effect in reducing breast cancer,[245] thus further studies are needed to clarify the effect of aspirin in cancer prevention.

    In gardening

    [edit]

    There are anecdotal reports that aspirin can improve the growth and resistance of plants,[246][247] though most research has involved salicylic acid instead of aspirin.[248]

    Veterinary medicine

    [edit]

    Aspirin is sometimes used in veterinary medicine as an anticoagulant or to relieve pain associated with musculoskeletal inflammation or osteoarthritis. Aspirin should be given to animals only under the direct supervision of a veterinarian, as adverse effects—including gastrointestinal issues—are common. An aspirin overdose in any species may result in salicylate poisoning, characterized by hemorrhaging, seizures, coma, and even death.[249]

    Dogs are better able to tolerate aspirin than cats are.[250] Cats metabolize aspirin slowly because they lack the glucuronide conjugates that aid in the excretion of aspirin, making it potentially toxic if dosing is not spaced out properly.[249][251] No clinical signs of toxicosis occurred when cats were given 25 mg/kg of aspirin every 48 hours for 4 weeks,[250] but the recommended dose for relief of pain and fever and for treating blood clotting diseases in cats is 10 mg/kg every 48 hours to allow for metabolization