Metoprolol + Chlorthalidone Tablets

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Therapeutic Indication

Hypertension (moderate to severe)
Coronary artery disease
Angina pectoris
Atrial fibrillation
Post-myocardial infarction management
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Metoprolol + Chlorthalidone

Tablet

Combination of metoprolol and chlorthalidone shows synergistic action to control high blood pressure. Lowering blood pressure helps to reduce your risk of having a heart attack or a stroke in the future. Metoprolol is a selective beta-1 blocker which slows down the conduction of heart and decreases the blood pressure gradually. Chlorthalidone is a thiazide-like diuretic used for the treatment of hypertension and for management of edema caused by conditions such as heart failure or renal impairment. Chlorthalidone improves blood pressure and swelling by preventing water absorption from the kidneys through inhibition of the Na+/Cl− symporter in the distal convoluted tubule cells in the kidney.

Speciality Cardiology | Internal Medicine
Tags Beta-blocker | Diuretic | Hypertension | Cardioprotection
Strength
  • Metoprolol 25 mg
  • Chlorthalidone 12.5 mg
Packing Size
  • 10 Tablets

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Mechanism

Metoprolol specifically inhibits beta-1 receptors which are specifically present on cardiac muscles. This inhibition decreases cardiac output by producing negative chronotropic and inotropic effects without presenting activity towards membrane stabilization nor intrinsic sympathomimetics hence decreasing the blood pressure.

Chlorthalidone prevents reabsorption of sodium and chloride through inhibition of the Na+/Cl- symporter in the cortical diluting segment of the ascending limb of the loop of Henle. Reduction of sodium reabsorption subsequently reduces extracellular fluid and plasma volume via an osmotic, sodium-driven diuresis. By increasing the delivery of sodium to the distal renal tubule, Chlorthalidone indirectly increases potassium excretion via the sodium-potassium exchange mechanism. It is thought that increased diuresis results in decreased plasma and extracellular fluid volume which therefore requires decreased cardiac output and overall lowers blood pressure. Chlorthalidone has also been shown to decrease platelet aggregation and vascular permeability, as well as promote angiogenesis in vitro, which is thought to be partly the result of reductions in carbonic anhydrase-dependent pathways. These pathways may play a role in chlorthalidone's cardiovascular risk reduction effects.

Pharmacokinetics

  • Metoprolol Succinate: Oral absorption nearly complete; bioavailability ~40% due to first-pass metabolism. Peak plasma concentration in 1.5–2 hours. Volume of distribution ~4.2 L/kg; protein binding ~11%. Metabolized in liver via CYP2D6; excreted mainly via urine (<5% unchanged). Half-life ~3–7 hours.
  • Chlorthalidone: Absorbed slowly but sustained; concentrates in erythrocytes. Protein binding ~75% (mainly albumin). Large volume of distribution; biphasic elimination. Excreted ~50% unchanged via kidney. Half-life ~40–50 hours, providing prolonged antihypertensive effect.
  • Combination: Provides synergistic blood pressure reduction and cardiovascular protection. Metoprolol reduces cardiac workload, while Chlorthalidone decreases plasma volume.

Side Effects

  • Dizziness
  • Fatigue
  • Depression
  • Insomnia
  • Diarrhea
  • Electrolyte imbalance (hyponatremia, hypokalemia)

Contraindication

  • Severe aortic stenosis
  • Acute kidney failure
  • Severe hepatic impairment
  • Uncontrolled diabetes mellitus
  • Pregnancy

Interaction

  • Antidepressants (fluoxetine, paroxetine, bupropion)
  • Antimalarials (hydroxychloroquine)
  • Cimetidine, ranitidine (increase metoprolol levels)
  • Clonidine, quinidine, propafenone (cardiac drugs)
  • Diphenhydramine (antihistamine)
  • Ritonavir (HIV drug)

Warning and Precautions

  • Monitor blood pressure and electrolytes regularly
  • Use under medical supervision only
  • Caution in elderly patients

Dosage

As directed by the Physician.