Mechanism of action of Mirabegron

Mechanism of Action of Mirabegron

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Introduction

Mirabegron is a β₃‑adrenergic receptor agonist used to treat overactive bladder (OAB). By selectively activating β₃‑receptors in the detrusor muscle of the bladder, it enhances urine storage and reduces urinary urgency and frequency without significantly affecting cardiovascular β₁ or β₂ receptors.

Mirabegron MOA
Mirabegron mechanism of action

Step-by-Step Mechanism of Action

  1. Selective β₃‑Agonism
    Mirabegron binds to β₃‑adrenergic receptors in the bladder detrusor muscle.
  2. Activation of Adenylyl Cyclase
    Receptor activation triggers Gs-protein pathways, increasing cAMP production.
  3. Detrusor Muscle Relaxation
    Elevated cAMP leads to relaxation of the detrusor muscle during bladder filling.
  4. Improved Bladder Sensitivity
    Relaxation increases bladder capacity and delays the activation threshold of stretch receptors.
  5. Urinary Symptom Relief
    The result is reduced urgency episodes, decreased frequency, and fewer incontinence events.
Mechanism of action of Mirabegron flowchart
Mirabegron mechanism of action flowchart

Pharmacokinetic Parameters

ParameterValue
Bioavailability~29% (fasting)
Peak Plasma Time (Tₘₐₓ)~3.5 hours
Half-Life~50 hours
Protein Binding~71%
MetabolismHepatic via CYP3A4 and CYP2D6
Excretion~55% fecal, ~45% renal

Clinical Uses

  • Treatment of overactive bladder with symptoms of urgency, frequency, or incontinence

Adverse Effects

  • Hypertension
  • Headache
  • Nasopharyngitis
  • Urinary tract infection
  • Constipation
  • Rare: tachycardia, dizziness

Comparative Analysis

FeatureMirabegronAntimuscarinics (e.g., oxybutynin)
Mechanismβ₃‑agonistMuscarinic receptor antagonist
Bladder RelaxationVia cAMP-mediated detrusor relaxationBlocks M₃ receptors inhibiting contraction
Dry Mouth RiskLowHigh
Constipation RiskLow–moderateModerate–high
Cardiovascular EffectsMild BP/HR increase possibleMinimal

MCQs

1. Mirabegron primarily targets which receptor?
A. β₁‑adrenergic
B. β₂‑adrenergic
C. β₃‑adrenergic
D. M₃‑muscarinic
Answer: C

2. Activation of β₃-receptors in the bladder increases:
A. Intracellular Ca²⁺
B. cAMP
C. IP₃
D. DAG
Answer: B

3. The therapeutic effect of mirabegron is:
A. Increased urination frequency
B. Detrusor muscle contraction
C. Detrusor muscle relaxation
D. Alpha receptor blockade
Answer: C

4. Common side effect of mirabegron includes:
A. Severe dry mouth
B. Hypertension
C. Mydriasis
D. Urinary retention
Answer: B

5. Its half-life is approximately:
A. 10 hours
B. 24 hours
C. 50 hours
D. 72 hours
Answer: C

6. Mirabegron is metabolized by:
A. CYP1A2 only
B. CYP2E1 only
C. CYP3A4 and CYP2D6
D. Renal excretion without metabolism
Answer: C

7. Compared to antimuscarinics, it has:
A. Higher dry mouth risk
B. Lower dry mouth risk
C. Same side effect profile
D. More anticholinergic effects
Answer: B

8. Mirabegron helps relieve:
A. Stress urinary incontinence
B. Overflow incontinence only
C. Overactive bladder symptoms
D. Neuropathic bladder
Answer: C

9. Which is not a common ADR?
A. Headache
B. Hypotension
C. Constipation
D. Nasopharyngitis
Answer: B

10. Urinary effects result from:
A. Calcium channel blockade
B. Sodium channel inhibition
C. β₃‑mediated detrusor relaxation
D. Muscarinic receptor stimulation
Answer: C

FAQs

1. Is mirabegron anticholinergic?
No, it works via β₃‑adrenergic receptors, not by blocking cholinergic receptors.

2. Can it raise blood pressure?
Yes, mild to moderate increases in BP may occur.

3. Can it be used in men with BPH?
Yes, it’s approved for overactive bladder in both men and women, including those with BPH.

4. When should it be taken?
Once daily, with or without food.

5. Are there drug interactions?
Yes—especially with CYP3A4 or CYP2D6 inhibitors or inducers; dosage adjustments may be needed.

References

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