Amlodipine – Calcium Channel Blocker

I. General Introduction

• Scientific name: Amlodipine besylate
• Drug class: Calcium channel blocker (DHP)
• Dosage forms: Tablets, capsules, intravenous solution
• Molecular formula: C20H25ClN2O5
• Molecular weight: 408.9 g/mol

II. Structure and Properties

• Chemical structure:
  • Amlodipine is a dihydropyridine derivative containing a secondary amine group (NH2) and a chlorine atom.
  • The amlodipine molecule is a racemic mixture of two enantiomers, (S)-amlodipine and (R)-amlodipine, but only the (S) enantiomer exhibits calcium channel blocking activity.
• Physical properties:
  • White crystalline powder, sparingly soluble in water but freely soluble in organic solvents.
  • Strong ultraviolet (UV) absorption.

III. Pharmacological Actions

• Mechanism of action:
  • Amlodipine selectively blocks L-type calcium channels in vascular smooth muscle, resulting in peripheral vasodilation, reduced peripheral vascular resistance, and decreased blood pressure.
  • Prolonged vasodilatory effects (8-12 hours) due to:
    • Cl group: Enhances lipophilicity, increasing absorption and slowing metabolism.
    • Bulky R2 substituent: Decreases metabolism rate, prolonging action.
    • NH2 group: Converts to NH3+ in the stomach, binding to proteins, forming stable complexes, and extending the duration of action.
• Pharmacological effects:
  • Lowering blood pressure
  • Reducing angina pain
  • Preventing angina attacks

IV. Pharmacokinetics

• Absorption:
  • Well absorbed orally (bioavailability 60-80%), food does not affect absorption.
  • Highly bound to plasma proteins (98%).
• Distribution:
  • Widely distributed throughout the body, with high concentrations in the liver, kidneys, and lungs.
• Metabolism:
  • Metabolized in the liver into inactive metabolites.
• Excretion:
  • Excreted in urine, mainly as metabolites.

V. Indications

• Treatment of hypertension (HTN):
  • Amlodipine is an effective antihypertensive drug, which can be used alone or in combination with other drugs.
  • It is recommended for patients with mild to moderate HTN, and can be used for patients with severe HTN if combined with other medications.
• Treatment of angina pectoris:
  • Amlodipine helps dilate blood vessels, reducing workload on the heart and relieving angina pain.
  • It can be used for patients with stable and unstable angina.

VI. Contraindications

• Untreated congestive heart failure:
  • Amlodipine may worsen heart failure.
• Hypersensitivity to amlodipine or other calcium channel blockers:
  • May cause allergic reactions and hypersensitivity.
• Pregnancy:
  • Amlodipine should be avoided during the first trimester of pregnancy as it may cause fetal malformations.
  • During the last trimester, amlodipine should be used only when absolutely necessary and after careful consideration of the benefits and risks.
• Breastfeeding:
  • Amlodipine may be excreted in breast milk, potentially affecting infants.

VII. Side Effects

• Common:
  • Ankle edema
  • Palpitations
  • Headache
  • Fatigue
  • Dizziness
  • Nausea
  • Diarrhea
  • Increased liver enzymes
• Rare:
  • Syncope
  • Cerebral hemorrhage
  • Heart failure
  • Hepatitis
  • Allergic reactions

VIII. Drug Interactions

• Increased amlodipine effects:
  • CYP3A4 inhibitors (such as ketoconazole, itraconazole)
  • Grapefruit juice
  • Antifungal medications
  • Macrolide antibiotics
• Decreased amlodipine effects:
  • CYP3A4 inducers (such as rifampicin, phenytoin)
• Increased risk of side effects:
  • ACE inhibitors (such as captopril, enalapril)
  • Diuretics (such as furosemide, hydrochlorothiazide)

IX. Precautions

• Dosage and administration: Dosage and administration of amlodipine depend on the condition, patient’s physical condition, and the type of combined medications.
  • Consult your doctor or pharmacist before using this medication.
• Patients with renal impairment: Dosage adjustment may be necessary.
• Patients with hepatic impairment: Use with caution.
• Elderly patients: Dosage adjustment may be necessary.
• Children: There is insufficient data regarding the safety and efficacy of amlodipine in children, hence its use should be avoided in children.
• Cautions:
  • Blood pressure should be monitored regularly during amlodipine therapy.
  • Do not stop taking the medication abruptly without your doctor’s instructions.
  • Inform your doctor about any side effects experienced during treatment.

X. Quantitation

• Common methods:
  • UV-Vis spectrophotometry: Based on amlodipine’s strong ultraviolet absorption.
  • High-performance liquid chromatography (HPLC): Accurate analysis and quantification.
  • Chemical reactions: Based on the reaction of the amine group (NH2) or the dihydropyridine ring with suitable reagents.

XI. Storage

• Store amlodipine at room temperature, in a dry and well-ventilated place, away from direct sunlight.
• Keep medication out of reach of children.

XII. Notes

• Amlodipine is an effective, safe, and easy-to-use antihypertensive medication.
• However, it may cause some side effects, so caution is required when using it.
• Consult your doctor or pharmacist before using amlodipine.
• Always follow your doctor’s instructions during treatment.