Pain & Inflammation Part 1.3

Indomethacin, an acetic acid derivative, is noted for what characteristic and uses?

• It is less potent than aspirin and primarily used for mild pain.

• It is a selective COX-2 inhibitor with a long half-life.

• It is the most potent inhibitor of prostaglandin synthesis (COX-1) and is used for acute gouty arthritis and ankylosing spondylitis.

• It is primarily an analgesic with no anti-inflammatory effect.

Besides inhibiting prostaglandin synthesis, what other enzymes may Indomethacin inhibit?

• COX-2 and TXA2.

• Phospholipase A and C.

• Interleukin-1 and Interleukin-6.

• Nitric oxide synthase and adhesion molecules.

Why are topical forms of Indomethacin often preferred, despite its oral absorption?

• It is poorly absorbed orally.

• It is not bound to plasma proteins.

• It is highly bound to plasma proteins, so topical forms are often preferred for local analgesic/anti-inflammatory effects.

• It has a very short half-life.

Which of the following are listed as adverse effects of Indomethacin?

• Agranulocytosis and aplastic anemia.

• GI problems, severe migraine, confusion, depression, and risk of fluid retention.

• Occult bleeding and renal tubular necrosis without hepatic issues.

• Diarrhea and abdominal pain (only).

Indomethacin is contraindicated in which patient populations?

• Patients with diabetes and hypertension.

• Patients with peptic ulcer and gastrointestinal irritation.

• Pregnant patients (due to premature closure of the patent ductus arteriosus, PDA, in the fetus) and in patients with psychosis.

• Children with chickenpox or influenza B virus infection.

What is noted about Sulindac?

• It is an active drug that is converted into a prodrug in the liver.

• It has a distinct indication and toxicity profile from indomethacin.

• It is a prodrug closely related to indomethacin, converted to its active form in the liver, with similar indications and toxicity profile.

• It is an anthranilic acid derivative with a short half-life.

What is noted about Diclofenac?

• It is contraindicated in nursing mothers but safe for children and pregnant women.

• It does not accumulate in synovial fluid.

• It accumulates in synovial fluid after oral administration, high doses can impair renal function, and it is contraindicated in children, pregnant women, and nursing mothers.

• It is primarily used to replace morphine for post-surgical pain.

Which of the following are Anthranilic Acid Derivatives, and for what are they commonly used?

• Diclofenac and Indomethacin; used for rheumatoid arthritis.

• Mefenamic Acid (e.g., Ponstan) and Flufenamic Acid; common over-the-counter drugs for dysmenorrhea and inflammation.

• Ibuprofen and Naproxen; used for acute gout.

• Meloxicam and Piroxicam; used for peptic ulcers.

What are the key pharmacokinetic and adverse effect characteristics of Anthranilic Acid Derivatives like Mefenamic Acid?

• Long half-life, allowing once-daily dosing; commonly cause severe migraine.

• Short half-life, requiring dosing every 6 hours; can cause diarrhea and abdominal pain.

• Poorly absorbed orally; primarily cause agranulocytosis.

• Metabolized in the kidneys; enhance the effect of oral hypoglycemics.

Which drug interaction is a key concern with Anthranilic Acid Derivatives?

• They decrease the effect of oral anticoagulants.

• They are safe to use concurrently with aspirin, warfarin, or heparin.

• They primarily interact with barbiturates.

• They enhance the effect of oral anticoagulants, so avoid concurrent use with aspirin, warfarin, or heparin.