Table of Contents
Introduction
Mesalazine (also known as mesalamine or 5-aminosalicylic acid, 5-ASA) is an anti-inflammatory drug used primarily in the management of inflammatory bowel diseases such as ulcerative colitis and mild Crohn disease. It acts locally within the intestinal mucosa to reduce inflammation and promote mucosal healing. Its targeted action in the gut makes it effective with relatively fewer systemic side effects.
Mechanism of Action (Step-wise)
- Mesalazine is released in the intestinal lumen from specially formulated oral or rectal preparations.
- It acts locally on the intestinal mucosa rather than systemically.
- It inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis.
- It inhibits lipoxygenase pathways, decreasing leukotriene production.
- This leads to reduced inflammatory mediator release in the gut.
- Mesalazine scavenges free radicals and reactive oxygen species.
- It inhibits activation of nuclear factor-kappa B (NF-κB).
- This reduces transcription of pro-inflammatory cytokines such as TNF-α and interleukins.
- It promotes mucosal healing and reduces inflammation in the colon.
A key exam point is that mesalazine acts locally to inhibit prostaglandins, leukotrienes, and inflammatory cytokines.
Pharmacokinetics
Mesalazine is administered orally or rectally. Oral formulations are designed to release the drug in the distal small intestine or colon using pH-dependent coatings or delayed-release systems. It is partially absorbed and metabolized to inactive acetylated metabolites in the intestinal mucosa and liver. Excretion occurs via urine and feces. Due to its local action, systemic bioavailability is relatively low.
Clinical Uses
Mesalazine is used in ulcerative colitis for both induction and maintenance of remission. It is also used in mild to moderate Crohn disease, particularly when the colon is involved. Rectal preparations are useful for distal disease such as proctitis. It helps relieve symptoms, reduce inflammation, and prevent relapse.
Adverse Effects
Mesalazine is generally well tolerated. Common adverse effects include headache, nausea, abdominal pain, and diarrhea. Rare but serious adverse effects include nephrotoxicity, pancreatitis, and hypersensitivity reactions. Renal function should be monitored during long-term use.
Comparative Analysis
| Feature | Mesalazine | Sulfasalazine | Corticosteroids |
|---|---|---|---|
| Class | 5-ASA derivative | 5-ASA + sulfapyridine | Steroid |
| Mechanism | Local anti-inflammatory | Same as mesalazine | Broad immunosuppression |
| Side effects | Mild | More (due to sulfapyridine) | Significant |
| Use | Mild–moderate IBD | Mild–moderate IBD | Moderate–severe IBD |
| Systemic effect | Minimal | Moderate | High |
Mesalazine differs from sulfasalazine by lacking the sulfapyridine component, which reduces adverse effects. Compared to corticosteroids, it has a localized action and is safer for long-term use.
MCQs
- Mesalazine is also known as:
a) 4-ASA
b) 5-ASA
c) 6-ASA
d) 3-ASA
Answer: b) 5-ASA
- Mesalazine primarily acts on:
a) Brain
b) Kidney
c) Intestinal mucosa
d) Liver
Answer: c) Intestinal mucosa
- Mesalazine inhibits which enzyme pathway?
a) Glycolysis
b) Cyclooxygenase
c) Krebs cycle
d) Urea cycle
Answer: b) Cyclooxygenase
- It also inhibits:
a) Lipoxygenase
b) ATP synthesis
c) DNA replication
d) Protein synthesis
Answer: a) Lipoxygenase
- Mesalazine reduces:
a) Prostaglandins and leukotrienes
b) Insulin
c) Dopamine
d) Calcium
Answer: a) Prostaglandins and leukotrienes
- Mesalazine is used in:
a) Asthma
b) Ulcerative colitis
c) Hypertension
d) Diabetes
Answer: b) Ulcerative colitis
- Mesalazine acts:
a) Systemically
b) Locally
c) In CNS
d) In blood
Answer: b) Locally
- A common adverse effect is:
a) Hypoglycemia
b) Headache
c) Hypercalcemia
d) Bradycardia
Answer: b) Headache
- A serious adverse effect is:
a) Nephrotoxicity
b) Hypernatremia
c) Hypokalemia
d) Arrhythmia
Answer: a) Nephrotoxicity
- Mesalazine inhibits which transcription factor?
a) NF-κB
b) DNA polymerase
c) RNA polymerase
d) ATP synthase
Answer: a) NF-κB
- Compared to sulfasalazine, mesalazine has:
a) More side effects
b) Fewer side effects
c) Same side effects
d) No effect
Answer: b) Fewer side effects
- Mesalazine promotes:
a) Inflammation
b) Infection
c) Mucosal healing
d) Fibrosis
Answer: c) Mucosal healing
FAQs
What is the mechanism of action of mesalazine?
It reduces inflammation by inhibiting prostaglandins, leukotrienes, and cytokine production in the gut.
Is mesalazine the same as mesalamine?
Yes, both refer to 5-aminosalicylic acid.
Why does mesalazine act locally?
It is formulated to release in the intestine with minimal systemic absorption.
What conditions is it used for?
Ulcerative colitis and mild Crohn disease.
What is a major adverse effect?
Nephrotoxicity.
Why is renal monitoring needed?
Because long-term use can affect kidney function.
References
Goodman & Gilman’s The Pharmacological Basis of Therapeutics – Anti-inflammatory Drugs
https://accessmedicine.mhmedical.com/book.aspx?bookid=3191
Katzung: Basic and Clinical Pharmacology – GI Anti-inflammatory Drugs
https://accessmedicine.mhmedical.com/content.aspx?bookid=3382
Tripathi: Essentials of Medical Pharmacology – Anti-inflammatory Drugs
https://www.jaypeedigital.com
Harrison’s Principles of Internal Medicine – Inflammatory Bowel Disease
https://accessmedicine.mhmedical.com
