Mechanism of Action of Dicyclomine

Introduction

Dicyclomine (dicycloverine) is an anticholinergic antispasmodic agent primarily used in the management of irritable bowel syndrome (IBS) and other functional gastrointestinal disorders. It relieves abdominal pain and cramping by reducing smooth muscle spasm in the gastrointestinal tract. Dicyclomine is a high-yield drug in pharmacology and gastroenterology examinations because of its muscarinic receptor antagonism and characteristic anticholinergic adverse effects.

Mechanism of Action (Step-wise)

Dicyclomine reduces gastrointestinal smooth muscle spasm by blocking muscarinic receptors.

Step-wise mechanism:

1. Parasympathetic Control of GI Motility
   Gastrointestinal smooth muscle contraction is mediated by acetylcholine acting on muscarinic (M₃) receptors.
2. Muscarinic Receptor Antagonism
   Dicyclomine competitively antagonizes muscarinic receptors on GI smooth muscle.
3. Inhibition of Acetylcholine Action
   Blocking muscarinic receptors prevents acetylcholine-induced smooth muscle contraction.
4. Reduced Intracellular Calcium
   Muscarinic blockade decreases calcium influx into smooth muscle cells.
5. Relaxation of GI Smooth Muscle
   Decreased calcium availability leads to reduced tone and spasm of intestinal smooth muscle.
6. Reduction in GI Motility and Spasm
   Intestinal hypermotility and spasmodic contractions are suppressed.
7. Relief of Abdominal Pain
   Decreased spasm results in symptomatic relief of cramping and abdominal discomfort.

Pharmacokinetics

• Absorption: Well absorbed orally
• Distribution: Widely distributed; crosses blood–brain barrier
• Metabolism: Hepatic metabolism
• Elimination: Renal excretion
• Half-life: Approximately 1.8 hours
• Onset of action: Rapid (within 1–2 hours)

Clinical Uses

Dicyclomine is primarily used in functional gastrointestinal disorders:

• Irritable bowel syndrome (IBS)
• Intestinal colic
• Functional bowel spasm
• Abdominal cramping due to hypermotility

It is not effective in inflammatory bowel disease or mechanical obstruction.

Adverse Effects

Adverse effects are related to anticholinergic activity:

• Central nervous system:
  • Dizziness
  • Drowsiness
  • Confusion (elderly)
• Peripheral anticholinergic effects:
  • Dry mouth
  • Blurred vision
  • Constipation
  • Urinary retention
  • Tachycardia

Dicyclomine should be used cautiously in elderly patients and those with glaucoma or prostatic hypertrophy.

Comparative Analysis (must include a table + explanation)

Comparison of Antispasmodic Agents

Explanation:
Dicyclomine provides effective relief of GI spasm with fewer CNS effects than hyoscine. Peppermint oil offers a non-anticholinergic alternative but may be less potent in severe symptoms.

MCQs (10–15)

1. Dicyclomine relieves abdominal pain by:
   a) Increasing GI motility
   b) Blocking opioid receptors
   c) Blocking muscarinic receptors
   d) Inhibiting prostaglandin synthesis

Answer: c) Blocking muscarinic receptors

2. The primary site of action of dicyclomine is:
   a) Central nervous system
   b) Neuromuscular junction
   c) GI smooth muscle
   d) Enteric neurons only

Answer: c) GI smooth muscle

3. Dicyclomine decreases intestinal spasm by reducing:
   a) Sodium influx
   b) Potassium efflux
   c) Calcium influx
   d) Chloride secretion

Answer: c) Calcium influx

4. Dicyclomine is most commonly used in:
   a) Peptic ulcer disease
   b) Irritable bowel syndrome
   c) Ulcerative colitis
   d) Crohn disease

Answer: b) Irritable bowel syndrome

5. Dicyclomine belongs to which drug class?
   a) Opioid analgesic
   b) Antispasmodic anticholinergic
   c) Prokinetic agent
   d) H₂ receptor blocker

Answer: b) Antispasmodic anticholinergic

6. A common adverse effect of dicyclomine is:
   a) Diarrhea
   b) Bradycardia
   c) Dry mouth
   d) Hypotension

Answer: c) Dry mouth

7. Dicyclomine reduces GI motility by inhibiting:
   a) Sympathetic activity
   b) Parasympathetic activity
   c) Enteroendocrine hormones
   d) Nitric oxide synthesis

Answer: b) Parasympathetic activity

8. Dicyclomine should be avoided in patients with:
   a) IBS
   b) Glaucoma
   c) Mild diarrhea
   d) Dyspepsia

Answer: b) Glaucoma

9. Which receptor subtype is mainly blocked by dicyclomine?
   a) M₁
   b) M₂
   c) M₃
   d) Nicotinic

Answer: c) M₃

10. Dicyclomine differs from peppermint oil because it:
    a) Has no effect on smooth muscle
    b) Is anticholinergic
    c) Is prokinetic
    d) Causes diarrhea

Answer: b) Is anticholinergic

FAQs (minimum 5)

1. What is the primary mechanism of dicyclomine?
   Competitive antagonism of muscarinic receptors in GI smooth muscle.
2. Why is dicyclomine effective in IBS?
   It reduces intestinal smooth muscle spasm and abdominal pain.
3. Does dicyclomine affect GI secretion?
   Yes, it may reduce secretions due to anticholinergic action.
4. Can dicyclomine cause CNS effects?
   Yes, especially dizziness and confusion in elderly patients.
5. Is dicyclomine useful in inflammatory bowel disease?
   No, it is mainly used in functional bowel disorders.
6. Why should dicyclomine be used cautiously in glaucoma?
   Because anticholinergic effects can increase intraocular pressure.

References

• Goodman & Gilman’s The Pharmacological Basis of Therapeutics
  https://accessmedicine.mhmedical.com
• Katzung BG. Basic and Clinical Pharmacology
  https://accessmedicine.mhmedical.com
• Tripathi KD. Essentials of Medical Pharmacology
  https://www.jaypeebrothers.com
• Harrison’s Principles of Internal Medicine
  https://accessmedicine.mhmedical.com

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