Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

Introduction

Non-steroidal anti-inflammatory Drugs (NSAIDs) are a group of medications that are commonly used worldwide to manage pain, reduce inflammation and lower body temperature in fever. Inflammation is a complex biological response of the body to harmful stimuli such as pathogens, damaged cells or irritants, and is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. Inflammation can be classified as either acute or chronic.

NSAIDs work by inhibiting the action of enzymes called Cyclooxygenases (COX), which are responsible for the synthesis of prostaglandins. Prostaglandins are mediators of inflammation and also sensitize pain receptors, lowering their threshold of response to stimuli and allowing the other mediators of inflammation.

The NSAIDs can be grouped based on their chemical structures, which include salicylates, pyrazolone derivatives, indole derivatives, propionic acid derivatives, anthranilic acid derivatives, aryl-acetic acid derivatives, pyrrolo-pyrrolo derivatives, para-amino phenol derivatives, and benzoxazocine derivatives.

The most well-known NSAID is acetylsalicylic acid (Aspirin), which is a non-selective and irreversible inhibitor of COX. Aspirin is used for its analgesic, antipyretic and anti-inflammatory properties and also has a cardioprotective effect.

NSAIDs are absorbed well when taken orally and are 80% protein-bound. They slowly enter the brain, freely cross the placenta, are metabolized in the liver and are excreted through glomerular filtration and tubular secretion.

However, there are contraindications for the use of NSAIDs, including peptic ulcer, hypersensitivity, ulcerative colitis, gout, renal failure and haemophilia. Adverse reactions include gastrointestinal effects, Rey’s disease, hypersensitivity and salicylism.

The analgesic effect of NSAIDs is mild, being less potent than codeine, and is effective in non-visceral pain. The antipyretic effect is achieved by resetting the hypothalamic thermostat and rapidly reducing fever by heat loss. The metabolic effects are significant only at anti-inflammatory doses and increase cellular metabolism, heat production and utilization of glucose.

Respiration is stimulated by peripheral and central actions of NSAIDs at therapeutic doses. However, further increases cause respiratory depression and death due to respiratory failure. The acid-base and electrolyte balance, fluid and electrolyte balance, and renal function may also be affected.

Classification

They are classified into several categories based on their chemical structure:

1. Salicylates: e.g., Aspirin, Salsalate
2. Propionic acid derivatives: e.g., Ibuprofen, Naproxen, Ketoprofen
3. Acetic acid derivatives: e.g., Indomethacin, Diclofenac, Ketorolac
4. Enolic acid derivatives (Oxicams): e.g., Piroxicam, Meloxicam
5. Anthranilic acid derivatives (Fenamates): e.g., Mefenamic acid, Flufenamic acid
6. Selective COX-2 inhibitors: e.g., Celecoxib, Etoricoxib
7. Others: e.g., Paracetamol (Acetaminophen), Metamizole

Based on the selectivity to the COX enzyme:

NSAIDs can be classified into three main categories:

Non-selective NSAIDs

These drugs inhibit both COX-1 and COX-2 enzymes. Examples include aspirin, ibuprofen, and naproxen. Non-selective NSAIDs are widely used for their analgesic, anti-inflammatory, and antipyretic properties but can cause gastrointestinal side effects due to COX-1 inhibition.

Selective COX-2 inhibitors

Selective COX-2 inhibitors, like celecoxib, only target the COX-2 enzyme, which is responsible for inflammation and pain. They are designed to provide the same benefits as non-selective NSAIDs but with a lower risk of gastrointestinal side effects.

Topically used NSAIDs

These medications are applied directly to the skin and are used for localized pain relief. Examples include diclofenac gel and ketoprofen gel.

Aspirin

Aspirin, also known as acetylsalicylic acid, is one of the oldest and most widely used NSAIDs.

Pharmacological actions

Aspirin exerts its anti-inflammatory, analgesic, and antipyretic effects by irreversibly inhibiting the COX enzymes, decreasing prostaglandin production. In addition, aspirin has antiplatelet properties, as it inhibits the formation of thromboxane A2, which plays a crucial role in platelet aggregation.

Aspirin, also known as acetylsalicylic acid, is a salicylate and one of the most widely used NSAIDs.

Pharmacological actions:

1. Anti-inflammatory: Inhibits cyclooxygenase (COX) enzymes, reducing the production of prostaglandins, which play a role in inflammation.
2. Analgesic: Reduces pain by inhibiting prostaglandin synthesis in peripheral tissues.
3. Antipyretic: Lowers fever by inhibiting prostaglandin synthesis in the hypothalamus.
4. Antiplatelet: Inhibits platelet aggregation by irreversibly inhibiting the COX-1 enzyme, leading to reduced thromboxane A2 production.

Uses

Aspirin is commonly used to treat mild to moderate pain, fever, and inflammation. It is also used for the prevention of heart attacks, strokes, and other cardiovascular events in at-risk individuals due to its antiplatelet effects.

1. Pain relief (analgesic): Headaches, toothaches, menstrual cramps, and muscle pain.
2. Inflammation reduction (antiinflammatory): Arthritis, sprains, and other inflammatory conditions.
3. Fever reduction (antipyretic).
4. Cardiovascular protection (antiplatelet): Low-dose aspirin is used to prevent myocardial infarction, stroke, and transient ischemic attacks in high-risk patients.

Adverse reactions

While aspirin is generally well-tolerated, some adverse reactions may occur, including gastrointestinal issues like stomach pain, heartburn, and ulcers. Other potential side effects include bleeding, tinnitus (ringing in the ears), and allergic reactions.

1. Gastrointestinal: Gastric irritation, ulceration, bleeding, and nausea.
2. Bleeding: Prolonged bleeding time due to antiplatelet effects.
3. Hypersensitivity: Allergic reactions, asthma exacerbation, and anaphylaxis in susceptible individuals.
4. Reye’s syndrome: Rare but severe condition associated with aspirin use in children with viral infections.

Contraindications

Aspirin is contraindicated in individuals with a known allergy to aspirin or other NSAIDs, a history of gastrointestinal bleeding or ulcers, bleeding disorders, or those who are pregnant or breastfeeding. Aspirin should also be used with caution in patients with kidney or liver disease.

1. Active gastrointestinal bleeding or ulceration.
2. Known hypersensitivity to aspirin or other salicylates.
3. Asthma patients with a history of aspirin-induced bronchospasm.
4. Children and teenagers with viral infections (due to the risk of Reye’s syndrome).
5. Severe hepatic or renal impairment.

Other Important NSAIDs

Ibuprofen

Ibuprofen is a non-selective NSAID commonly used to treat pain, inflammation, and fever. It is available in both over-the-counter and prescription strengths.

Naproxen

Naproxen is another non-selective NSAID with similar uses to ibuprofen. It has a longer half-life than ibuprofen, which may provide longer-lasting pain relief.

Diclofenac

Diclofenac is a potent non-selective NSAID used for treating various types of pain and inflammation, including arthritis, gout, and postoperative pain. It is available in oral, topical, and injectable formulations.

Meloxicam

Preferentially inhibits COX-2 enzyme and is used for arthritis and other inflammatory conditions. It has a lower risk of gastrointestinal side effects compared to non-selective NSAIDs.

Paracetamol

Poisoning

Paracetamol, also known as acetaminophen, is a widely used analgesic and antipyretic drug. While generally safe when used as directed, excessive intake can lead to paracetamol poisoning, which can cause severe liver damage.

Paracetamol (Acetaminophen) poisoning can occur when an excessive amount of the drug is ingested, either accidentally or intentionally. It can lead to severe liver damage or acute liver failure.

Symptoms of paracetamol poisoning include nausea, vomiting, abdominal pain, and, in severe cases, jaundice, hepatic encephalopathy, and coagulopathy.

Treatment

Treatment for paracetamol poisoning may include activated charcoal to reduce absorption if administered within a few hours of ingestion and N-acetylcysteine (NAC) to replenish glutathione stores and prevent liver damage. In severe cases, liver transplantation may be necessary.

1. Activated charcoal: Administered within 1-2 hours of ingestion to reduce drug absorption.
2. N-acetylcysteine (NAC): The antidote for paracetamol poisoning, NAC replenishes glutathione stores and prevents liver damage. It is most effective when given within 8 hours of ingestion but can still be beneficial later in the course of poisoning.
3. Supportive care: Fluid resuscitation, electrolyte management, and liver and kidney function monitoring.
4. In severe cases, liver transplantation may be required.

Selective COX-2 Inhibitors

Selective COX-2 inhibitors target only the COX-2 enzyme, reducing inflammation and pain while minimizing gastrointestinal side effects associated with non-selective NSAIDs.

Examples

Examples of selective COX-2 inhibitors include celecoxib, rofecoxib (withdrawn from the market due to cardiovascular risks), and etoricoxib.

They have the following characteristics:

1. Anti-inflammatory: Effective in treating inflammatory conditions like arthritis.
2. Analgesic: Provide pain relief in various conditions.
3. Reduced gastrointestinal side effects: Lower risk of gastrointestinal bleeding and ulceration compared to non-selective NSAIDs, as they do not inhibit COX-1, which is responsible for maintaining gastric mucosal integrity.
4. Cardiovascular risk: Some selective COX-2 inhibitors (e.g., rofecoxib) have been withdrawn from the market due to an increased risk of cardiovascular events. Celecoxib and etoricoxib are still used but with caution in patients with a history of cardiovascular disease.

Topically Used NSAIDs

Topically used NSAIDs are medications that are applied directly to the skin, eyes, or other body surfaces to relieve pain and inflammation. They work by inhibiting the enzymes that produce prostaglandins, which are chemicals responsible for inflammation and pain.

Here are some examples of topical NSAIDs, including eye drops, and their uses:

1. Diclofenac gel (Voltaren, Solaraze):

• Used for the relief of pain associated with osteoarthritis, particularly in the hands, wrists, elbows, knees, ankles, and feet.
• Solaraze is specifically formulated to treat actinic keratosis, a type of precancerous skin lesion caused by sun damage.

2. Ibuprofen gel (Nurofen, Ibugel):

• Provides localized pain relief for minor aches and pains, such as sprains, strains, and sports injuries.
• Can also be used to alleviate pain from mild arthritis.

3. Ketoprofen gel (Orudis, Powergel):

• Used to treat inflammation and pain associated with musculoskeletal conditions, such as sprains, strains, and back pain.

4. Piroxicam gel (Feldene):

• Provides relief from pain and inflammation associated with musculoskeletal conditions and soft tissue injuries.

5. Flurbiprofen eye drops (Ocufen):

• Used to reduce inflammation and pain after eye surgery, such as cataract surgery.
• Can also be used to manage ocular inflammation caused by injury or infection.

6. Ketorolac eye drops (Acular, Acuvail):

• Prescribed to relieve eye pain, inflammation, and itching after eye surgery or due to seasonal allergies.

7. Nepafenac eye drops (Nevanac, Ilevro):

• Used to treat pain and inflammation following cataract surgery.
• Can also be prescribed for other types of ocular inflammation.

8. Bromfenac eye drops (Bromday, Prolensa, Xibrom):

• Reduces inflammation and pain after cataract surgery.
• Can also be used for other forms of ocular inflammation.

Topical NSAIDs are generally well tolerated, but some patients may experience localized skin reactions like rash, itching, or redness at the application site.

Disclaimer: This article is for informational purposes only and should not be taken as medical advice. Always consult with a healthcare professional before making any decisions related to medication or treatment.

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These medications play a crucial role in managing various medical conditions, such as pain from inflammation, arthritis, and menstrual cramps. Understanding the mechanisms of action, indications, and potential side effects of these drugs is essential for healthcare providers to provide effective care for their patients.

It is recommended to reinforce your understanding of NSAIDs through self-assessment. I suggest attempting a quiz or test, which does not collect any user data, to solidify your understanding and grasp important aspects of these drugs.

QUIZ: Please note that if you have any issues while attempting the quiz, either click on ‘Exit mobile version’ at the bottom of this page and redo the quiz or access it on desktops/laptops.