Aspirin

Aspirin, chemically known as acetylsalicylic acid (ASA), is one of the most widely used and historically significant drugs in modern medicine. It is valued for its analgesic (pain-relieving), antipyretic (fever-reducing), anti-inflammatory, and antiplatelet (blood-thinning) properties. Since its commercial introduction in the late 19th century, aspirin has become a cornerstone of pharmacotherapy, used in the treatment of a wide range of conditions, from headaches and arthritis to cardiovascular diseases.

Historical Background

The origins of aspirin trace back to ancient times. The use of willow bark and meadowsweet plants for pain relief and fever control was known to civilisations such as the Sumerians, Egyptians, Greeks, and Romans. The active component in these plants, salicin, was identified in the early 19th century.

• 1828: Johann Buchner, a German chemist, isolated salicin from willow bark.
• 1838: Italian chemist Raffaele Piria converted salicin into salicylic acid, the principal active compound responsible for its therapeutic effect.
• 1853: French chemist Charles Frédéric Gerhardt synthesised acetylsalicylic acid for the first time, though his method produced an unstable product.
• 1897: The modern form of aspirin was successfully synthesised and stabilised by Felix Hoffmann, a chemist at Bayer AG in Germany, who was seeking a less irritating alternative to salicylic acid for his father’s arthritis.

Bayer patented the process in 1899 and marketed the compound under the brand name Aspirin, derived from “A” for acetyl and “Spir” from Spiraea ulmaria (meadowsweet). The name soon became synonymous with the compound itself and eventually a generic term for acetylsalicylic acid worldwide.

Chemical Composition and Structure

• Chemical Name: 2-acetoxybenzoic acid (acetylsalicylic acid)
• Molecular Formula: C₉H₈O₄
• Molar Mass: 180.16 g/mol
• Structure: Consists of a benzene ring substituted with an ester group (–COOCH₃) and a carboxylic acid group (–COOH).

Aspirin is synthesised by acetylating salicylic acid with acetic anhydride in the presence of an acid catalyst, usually sulphuric acid or phosphoric acid.

Mechanism of Action

Aspirin exerts its pharmacological effects primarily by inhibiting the cyclooxygenase (COX) enzymes, COX-1 and COX-2, which play a key role in the biosynthesis of prostaglandins and thromboxanes.

• Prostaglandins are lipid compounds that mediate inflammation, pain, and fever.
• Thromboxanes facilitate platelet aggregation, leading to blood clot formation.

By acetylating a serine residue in the active site of the COX enzymes, aspirin irreversibly inhibits their function. This prevents the conversion of arachidonic acid into prostaglandins and thromboxanes, thereby:

• Reducing pain and inflammation.
• Lowering fever.
• Preventing platelet aggregation (hence reducing the risk of thrombosis).

Pharmacological Actions

1. Analgesic (Pain-Relieving): Aspirin alleviates mild to moderate pain such as headaches, toothaches, muscle pain, and menstrual cramps by reducing prostaglandin-mediated nerve sensitisation.
2. Antipyretic (Fever-Reducing): It acts on the hypothalamic heat-regulating centre, promoting vasodilation and sweating, which lower body temperature during fever.
3. Anti-Inflammatory: By suppressing prostaglandin synthesis, aspirin reduces tissue inflammation in conditions like rheumatoid arthritis and osteoarthritis.
4. Antiplatelet (Blood-Thinning): Low-dose aspirin irreversibly inhibits platelet aggregation, reducing the risk of heart attacks, strokes, and thrombosis. This effect lasts for the lifespan of the platelet (7–10 days).

Medical Uses

Aspirin is used both as a prescription and an over-the-counter (OTC) medication. Its applications include:

• Relief of mild to moderate pain and fever.
• Treatment of inflammatory conditions such as rheumatic fever, arthritis, and tendinitis.
• Prevention of myocardial infarction (heart attack) and ischemic stroke in high-risk patients.
• Management of unstable angina and after coronary artery bypass grafting (CABG) or angioplasty.
• In low doses (typically 75–150 mg/day), as a long-term cardiovascular prophylactic agent.

Dosage and Formulations

Aspirin is available in various formulations depending on therapeutic use:

• Tablets: 75 mg (low-dose), 300–500 mg (regular).
• Enteric-coated tablets: Designed to dissolve in the intestine, reducing gastric irritation.
• Effervescent tablets and powders: For faster relief of pain or fever.
• Combination formulations: Often combined with other analgesics like paracetamol or caffeine.

Adverse Effects and Precautions

While generally safe when used appropriately, aspirin can produce side effects, especially at high doses or with prolonged use. Common and serious adverse effects include:

• Gastrointestinal Irritation: Nausea, heartburn, and gastric ulceration due to inhibition of COX-1, which normally protects the stomach lining.
• Bleeding Risk: Prolonged bleeding time due to antiplatelet action.
• Allergic Reactions: Including asthma exacerbations and skin rashes (in aspirin-sensitive individuals).
• Reye’s Syndrome: A rare but serious condition causing liver and brain damage in children given aspirin during viral infections (e.g., influenza, chickenpox). Hence, aspirin is contraindicated in children under 12 years.
• Kidney and Liver Effects: High doses can impair renal and hepatic function.

Contraindications

Aspirin should be avoided or used with caution in:

• Peptic ulcer disease.
• Bleeding disorders (e.g., haemophilia).
• Hypersensitivity to salicylates or NSAIDs.
• Children and teenagers with viral infections.
• Pregnant women, particularly in the third trimester, due to risk of delayed labour and foetal complications.

Interactions

Aspirin can interact with several drugs:

• Anticoagulants (e.g., warfarin): Increased bleeding risk.
• Corticosteroids: Enhanced gastrointestinal irritation.
• Other NSAIDs: Increased risk of gastric and renal toxicity.
• Antihypertensive drugs: May reduce their effectiveness.

Recent Developments and Research

Modern research continues to explore aspirin’s broader potential. Studies have investigated its role in:

• Cancer prevention: Some evidence suggests that long-term low-dose aspirin may reduce the risk of colorectal cancer and other malignancies by inhibiting inflammation and abnormal cell growth.
• Neuroprotection: Research into its role in preventing Alzheimer’s disease and cognitive decline remains inconclusive.
• COVID-19 management: Early investigations considered aspirin’s antiplatelet properties for managing coagulopathy in severe infections, though results remain mixed.

Mechanistic Variations with Other NSAIDs

Unlike most non-steroidal anti-inflammatory drugs (NSAIDs), which reversibly inhibit COX enzymes, aspirin causes irreversible acetylation. This makes its antiplatelet effect unique and long-lasting, distinguishing it from ibuprofen or naproxen.

Public Health and Global Impact

Aspirin remains one of the most widely used and affordable medicines globally, included in the World Health Organization’s Model List of Essential Medicines. Its accessibility and versatility have made it indispensable in both developed and developing nations.
It is estimated that over 40,000 metric tonnes of aspirin are consumed annually worldwide. Despite over a century of use, it continues to be central to preventive cardiology and general healthcare.