Questions

Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, inflammation, and fever. It is commonly prescribed for conditions such as arthritis, gout, and other inflammatory disorders.

Mechanism of Action:

Indomethacin works by inhibiting the action of cyclooxygenase (COX) enzymes, particularly COX-1 and COX-2. These enzymes are responsible for the production of prostaglandins, which are chemicals in the body that promote inflammation, pain, and fever. By inhibiting COX enzymes, indomethacin reduces the production of prostaglandins, thereby helping to decrease inflammation, relieve pain, and lower fever.

Indications:

Indomethacin is used to treat various inflammatory conditions, including:

1. Arthritis:
   • Rheumatoid arthritis: Chronic autoimmune disease causing inflammation of the joints.
   • Osteoarthritis: Degeneration of joint cartilage and underlying bone, leading to pain and stiffness.
   • Ankylosing spondylitis: A form of arthritis that primarily affects the spine.
2. Gout: A type of arthritis caused by the accumulation of uric acid crystals in the joints.
3. Tendonitis and bursitis: Inflammation of the tendons or the fluid-filled sacs (bursae) that cushion the joints.
4. Pain management: For short-term relief of mild to moderate pain, such as muscle pain or dental pain.
5. Patent ductus arteriosus (PDA) in newborns: Indomethacin is used to treat this condition, which involves a blood vessel in the heart remaining open after birth.

Dosage and Administration:

Indomethacin is typically administered orally in the form of capsules, tablets, or suspensions. It is also available as an intravenous (IV) preparation and rectal suppositories in certain cases.

• The usual oral dose for adults ranges from 25 mg to 50 mg, taken two to three times daily.
• Maximum daily dose: Generally 200 mg (depending on the condition being treated).
• It should be taken with food or milk to reduce gastrointestinal irritation.

For gout attacks, higher doses may be used initially (e.g., 50 mg every 8 hours) until symptoms improve.

Side Effects:

Indomethacin can cause a variety of side effects, some of which may be severe. Common side effects include:

1. Gastrointestinal issues:
   • Upset stomach, nausea, vomiting, or diarrhea.
   • Gastric ulcers, bleeding, or perforation: Long-term use can increase the risk of serious stomach or intestinal problems.
2. Headache: Indomethacin is often associated with headaches, which can sometimes be severe.
3. Dizziness or drowsiness: Some patients may experience light-headedness or sedation.
4. Rash: Skin reactions like rashes or itching.
5. Fluid retention: Swelling in the hands, feet, or ankles may occur due to fluid retention.

Serious Side Effects:

While less common, indomethacin may cause more serious adverse effects, such as:

1. Cardiovascular risks:
   • Increased risk of heart attack or stroke, especially with long-term or high-dose use.
   • Hypertension (high blood pressure): Indomethacin can raise blood pressure.
2. Kidney problems:
   • Can lead to kidney damage, including acute kidney injury, particularly in patients with pre-existing kidney issues or those using other medications that affect kidney function.
3. Liver issues:
   • Can cause liver enzyme elevation and in rare cases, liver failure.
4. Severe allergic reactions:
   • Symptoms like difficulty breathing, swelling of the face or throat, and hives. These require immediate medical attention.
5. Gastrointestinal bleeding:
   • Serious GI bleeding, ulcers, or perforation, particularly in older adults or those with a history of GI disorders.

Contraindications:

Indomethacin should not be used in certain situations, including:

• Allergy to indomethacin or other NSAIDs.
• Active gastrointestinal bleeding or ulceration.
• Severe heart failure, as it can worsen fluid retention and increase the workload on the heart.
• Severe liver or kidney disease.
• Pregnancy, especially in the third trimester, as it can cause premature closure of the ductus arteriosus in the fetus.

Drug Interactions:

Indomethacin can interact with several other medications, including:

1. Anticoagulants (e.g., warfarin): Increased risk of bleeding.
2. Antihypertensives: Indomethacin may reduce the effectiveness of blood pressure-lowering medications like ACE inhibitors, angiotensin receptor blockers (ARBs), and diuretics.
3. Other NSAIDs or corticosteroids: Increased risk of gastrointestinal problems.
4. Lithium: Indomethacin can increase the blood levels of lithium, potentially leading to toxicity.
5. Methotrexate: Increases the risk of methotrexate toxicity.

Monitoring:

Patients on indomethacin, especially for long-term use, should undergo regular monitoring, including:

1. Liver function tests and renal function tests (including serum creatinine).
2. Complete blood count (CBC) to check for signs of anemia or bleeding.
3. Blood pressure monitoring to detect hypertension.

Special Considerations:

• Elderly patients: Older adults are more likely to experience side effects, especially gastrointestinal issues, cardiovascular risks, and kidney problems.
• Pregnancy: Indomethacin is contraindicated during the third trimester of pregnancy due to the risk of fetal harm, including premature closure of the ductus arteriosus. It should be used during pregnancy only if absolutely necessary and under the guidance of a healthcare provider.
• Breastfeeding: Indomethacin is excreted in breast milk, and caution is advised when used by breastfeeding mothers.

Summary:

Indomethacin is a potent NSAID used for the treatment of pain and inflammation associated with conditions like arthritis, gout, and tendonitis. While effective, it can have significant side effects, particularly in the gastrointestinal, cardiovascular, and renal systems. It is important to take it with food, monitor for side effects, and avoid using it in certain conditions, such as active gastrointestinal bleeding, severe kidney or liver disease, or during pregnancy. Regular follow-up with a healthcare provider is important for those using indomethacin, especially for long-term therapy.