Aspirin word was derived from Acetyl and Spirsaure. Letter “A” was derived from acetyl, while “Spir” came from the German word Spirsaure. Since Aspirin is an OTC (over the counter) drug, anyone can purchase this medicine from grocery or pharmacy store without the requirement of a prescription. Its first therapeutic effect was noticed by Hippocrates, a Greek Physician (460-377 BC) who found and wrote that “willow leaves and bark relieved pain and fevers”. Even the ancient Egyptians used willow bark for the relief of aches and pains, as mentioned by Diarmuid Jeffreys, author of “Aspirin: The Remarkable Story of a Wonder Drug.”
Finally, Aspirin was clinically noticed by John Vane, who received a Noble prize for discovering “prostaglandins and related biologically active substances” by highlighting the role of aspirin as antiplatelets. Officially Aspirin was launched by Bayer in 1899 AD. The trademark on the Aspirin is held by Bayer, where the company claimed that any Physician prescribing aspirin should prescribe the Bayer brand. Even in modern times also, 70 countries along with Germany use Bayer AG marked Aspirin only. Can you imagine, roughly 35,000 metric tonnes or over 100 billion aspirin tablets are manufactured and consumed every year.
The story of Reverse engineering of Aspirin:
In 1897, acetylsalicylic acid (ASA) was synthesized in its pure stable chemical form for the first time. The transformation of Aspirin from its analgesic to antiplatelet role spans for more than 80 years. Before 1940, the role of Aspirin was limited to analgesic activity only. In the same year, Karl Link reported the antithrombotic and anticoagulant activity of Aspirin. Later, in 1948, Gibson proposed the therapeutic use of Aspirin in cardiovascular diseases. The main credit of discovering Aspirin as an antithrombotic agent goes to Craven in 1948, when he himself tested it on his MI (Myocardial Infarction) affected patients. In 1950, Craven published his research work, where he mentioned the therapeutic effect of Aspirin against MI and stroke (Cardiovascular diseases).
The antiplatelet activity of Aspirin was discovered by Weiss in 1967, where he observed that Aspirin inhibited platelet activation by collagen. In addition to it, he also found that the wonder drug has irreversible antiplatelet effect for the full lifetime of that affected platelet. Brien also supported his theory of acetyl modification, where aspirin was found to have caused the antiplatelet effect.
How does Aspirin work?
As an analgesic: Our body has several pain mediators like cytokines, prostaglandin, leukotrienes which helps our body to feel pain. Aspirin lowers the inflammation causing these pain mediators in response to infection or injury thereby relieving pain and swelling. So, Aspirin is regarded as the drug of the first choice for treatment of a migraine and tension-type headache. Besides this, Aspirin is regarded as a weak antipyretic as, it indirectly interacts with physiological temperature control, mediated by salicylate associated with sweating i.e. increased heat loss from the body.
As an antiplatelet: Heart attacks result from deposition of excessive cholesterol or plaques within arteries (blood vessels) around the heart. These plaques start blocking the artery which obstructs the smooth blood flow leading to the blood clot in the heart arteries. This decrease the supply of oxygen in the heart tissues leading to angina (chest pain) followed by the heart attack. So, Aspirin acts as an antiplatelet which stops blood to clot in arteries of the heart by inhibiting thromboxane (blood clotting agent).
Latest recommendation on the therapeutic use of Aspirin:
In the year 2016, US Preventive Services Task Force (USPSTF) formulated and modified the recommendations for the primary prevention of Cardio Vascular Diseases (CVD) by using Aspirin. Following are the recommendation summary of USPSTF which are based on the published clinical data.
- For age groups (50-59): High recommendation of aspirin intake for the patient with life expectancy of 10 years, associated with high risk of heart diseases and no risk of Gastro bleeding.
•For age groups (60-69): High recommendation of aspirin intake in patients who have the high risk of CVD, willing to take low-dose aspirin daily for at least 10 years are more likely to get a benefit.
Note: For age groups (less than 50 years and greater than 70 years), so far no clinical data is available for a recommendation of intake of daily aspirin.
Difference between High dose and Low dose Aspirin:
Aspirin is divided into two dosages based regimen by several clinicians and researchers i.e. Low dose and High dose Aspirin. High dose Aspirin is generally prescribed for the relieving pain, on the other hand, Low-dose aspirin is usually prescribed for preventing the blood clot in cardiovascular diseases.
If we have a look towards clinical studies of dose-dependent Aspirin then data from 2,21,199 patients with 40.2 % MI (Myocardial Infarction) from 525 hospitals enrolled in the ACTION Registry – GWTG, the investigation defined high-dose aspirin as 325 mg and low-dose aspirin as 81 mg. Approximately half of adults of the USA and 40 % of UK population takes the low dose Aspirin ranging from 80 – 325 mg for dealing heart diseases. Scientific study namely BRAVO and CURE proved that bleeding process is independent of the dose/strength of Aspirin, even when the dose was less than 325 mg.FDA considers low dose (75-160mg) of Aspirin per day for a patient with 10 years the high risk of Coronary Heart Disease (CHD) > 10%.
Side effects of Aspirin and its mitigation:
High doses, daily intake of Aspirin causes bleeding by prolonging the Prothrombin time. It was Binz, a German scientist who observed in 1891 that, Aspirin caused mucosal bleeding in patients. This was the reason in the late 1940s, Aspirin was administered with Vitamin K to slow down the bleeding. But, after the discovery of advanced anti-ulcer medications like H2 antagonist (Ranitidine, Cimetidine etc.),
Proton pump inhibitors (pantoprazole, esomeprazole, rabeprazole, lansoprazole, omeprazole etc.), a risk of bleeding lowered in patients who were on the daily dose of Aspirin therapy. Besides this, some of the adverse drug reactions of daily intake of Aspirin include:
- Haemorrhage of the peptic ulcers.
- Increased risk of bleeding stroke.
- Reye’s syndrome in children.
Understanding Aspirin resistance:
In a simple word, Aspirin resistance refers to the lack of antiplatelet effect in spite of daily therapeutic doses of aspirin (75mg-150mg). This lack of antiplatelet effect of Aspirin can lead to increased risk and deaths due to cardiovascular diseases. However to detect the Aspirin resistance in an individual, one can undergo pathological tests of platelet thromboxane A2 production or platelet function. However, if the Aspirin resistance persists in any individual, Doctors usually advised them to switch to other antiplatelet medications like Clopidogrel bisulfate.
Role of Aspirin in Cardiovascular diseases:
Aspirin is indicated for the prevention and treatment of primary and secondary prevention of Percutaneous coronary intervention (PCI), Coronary artery bypass graft (CABG) surgery, Peripheral arterial disease (PAD), Extra-cranial arterial disease, Mechanical heart valve replacement and Pericarditis as per published data.
Role of Aspirin in treating Pre-eclampsia in pregnant women:
Low daily dose aspirin taken during the 3 rd trimester of pregnancy reduced the incidence of pregnancy-induced hypertension (PIH) and pre-eclampsia in women. Low dose Aspirin is also useful for pregnant women especially in case of Pre-eclampsia, which is a multisystem disease linked with elevated blood pressure and proteinuria (excess protein in the urine). The US Preventive Services Task Force (USPSTF) recommends the low-dose aspirin (81 mg/day) as preventive medication after a period of 12 weeks of gestation in women population, who are at high risk for pre-eclampsia. So, daily intake of Aspirin (81 mg/day) can cut down the risk of pre-eclampsia in pregnant women to 24%.
Aspirin in the new role of Anticancer against Colon cancer:
It has been now confirmed that Aspirin can be used for the treatment of Colorectal cancer as per several published clinical trials data. An ongoing ASCOLT Study comprised of 1200 participants which determine that, Aspirin in patients with dukes C or high-risk Dukes B colorectal cancer (ASCOLT) can improve survival rate in this patient. According to the Journal of the Royal Society Interface, “Regular use of Aspirin has shown to lower the incidence of various kinds of Cancers including Colon cancer”. However, USFDA has not approved aspirin for CRC prevention but recommends to be used after Physician advice. A study published in Journal of Clinical Oncology in August 2017, also advocates the regular use of (Painkiller) Aspirin in long-term Cancer survivors, as it improved overall 40% survival rates in
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