Amlodipine

Amlodipine is a medication in the calcium antagonist class that is used to treat high blood pressure (hypertension) and angina pectoris (chest pain caused by ischemia of the heart muscle). It works by blocking calcium from entering the muscles of the blood vessels and heart, causing them to relax and dilate. This improves blood flow and allows the heart to pump blood more easily, lowering the pressure in the blood vessels and reducing the workload on the heart.

Amlodipine can be used in monotherapy or in combination with other antihypertensive drugs to achieve target blood pressure values. In addition, it may be prescribed to patients with angina pectoris to prevent chest pain attacks.

This drug is available in the form of oral tablets and can be used either daily or as prescribed by a doctor. It is important to use amlodipine strictly according to your doctor's recommendations and not to stop taking it without his consent, even if you experience improvement.

Indications Amlodipine

1. Hypertension (high blood pressure): Amlodipine is used to lower blood pressure in patients with hypertension. It helps prevent complications associated with high blood pressure such as stroke, heart attack, and kidney problems.
2. Angina (stable and variant): Amlodipine may be used to treat stable and variant angina, which can be manifested by chest pain or discomfort during physical activity or stressful situations.
3. Vasospasms: Amlodipine may be used to prevent and treat vasospasms such as vasospasm from subarachnoid hemorrhage or coronary spasm.

Release form

1. Tablets for oral administration:

   • The most common form of release of amlodipine is oral tablets.
   • Dosage: Tablets usually contain 2.5 mg, 5 mg, or 10 mg of amlodipine (in the form of amlodipine besylate).
   • Tablets can be plain or coated to improve absorption and reduce side effects.

2. Modified-release tablets:

   • Controlled/modified-release tablets of amlodipine are also available, which provide a more even release of the medication throughout the day.

Pharmacodynamics

1. Blocking L-type calcium channels: Amlodipine blocks L-type calcium channels in vascular smooth muscle and myocardium. This leads to a decrease in intracellular calcium influx, which reduces the contractility of vascular smooth muscle and heart muscle.
2. Peripheral vascular dilation: Due to blockade of calcium channels in the smooth muscle of arteries and arterioles, amlodipine causes their dilation. This leads to a decrease in total peripheral vascular resistance and blood pressure.
3. Improvement of coronary blood flow: The dilation of coronary arteries under the influence of amlodipine contributes to increased blood flow in the myocardium, which may be particularly beneficial in patients with coronary heart disease.
4. Reduction of cardiac loading: By reducing cardiac muscle contractility and decreasing cardiac loading caused by vasodilation, amlodipine may improve cardiac function in patients with heart failure.
5. Minimal effect on conduction: Compared to some other calcium channel blockers, amlodipine generally has minimal effect on conduction in the conduction system of the heart, making it relatively safe for most patients with heart rhythm disorders.

Pharmacokinetics

1. Absorption: Amlodipine is usually rapidly and completely absorbed from the gastrointestinal tract after oral administration. It has a high bioavailability, about 60-65%.
2. Distribution: After absorption, amlodipine is rapidly distributed in body tissues. It is mainly bound to blood plasma proteins at a level of about 95%.
3. Metabolism: Amlodipine is metabolized in the liver with formation of inactive metabolites. The main metabolite is desethylamlodipine, which also has a blocking effect on calcium channels.
4. Excretion: Most of amlodipine and its metabolites are excreted through the kidneys (approximately 60-70% unchanged).
5. Half-life: The half-life of amlodipine from the body is about 30-50 hours, which means that its effects may continue for a long time after discontinuation.

Dosing and administration

Method of application

• Oral administration: Amlodipine is taken orally, regardless of meals. The tablets should be swallowed whole with plenty of water. The tablet should not be chewed or broken, especially if it is a modified-release tablet.

Dosage

For adults:

1. Hypertension (high blood pressure):

   • Starting dose: Usually 5 mg once daily.
   • Maintenance dose: Depending on the patient's response, the dose may be increased to a maximum dose of 10 mg per day.
   • Comment: In elderly patients, those with hepatic impairment, or when using amlodipine in combination with other drugs, the initial dose may be reduced to 2.5 mg daily.

2. Angina (chest pain):

   • Standard dose: Usually 5 mg once daily, which may be increased to 10 mg once daily depending on the patient's individual therapeutic response.

For children (ages 6 and up):

• Hypertension:
  • Starting dose: 2.5 mg once daily.
  • Maintenance dose: May be increased to 5 mg once daily after 1-2 weeks of treatment, depending on response to treatment.

Special Instructions

• Regular monitoring: Patients taking amlodipine need regular medical supervision to monitor the effectiveness and safety of treatment.
• Use during pregnancy: Amlodipine should be taken during pregnancy only if absolutely necessary under strict medical supervision.
• Interaction with other medicines: Amlodipine may interact with other medicines, which requires dose adjustment and medical supervision.

Use Amlodipine during pregnancy

The use of amlodipine during pregnancy can be problematic, especially in the first trimester when the baby's organs are forming. Amlodipine belongs to category C of the FDA pregnancy safety classification, which means that data on its safety in pregnant women are limited.

If you are taking amlodipine and become pregnant or plan to become pregnant, it is important to discuss this with your doctor. He or she will be able to assess the benefits of taking amlodipine compared with the potential risks to you and your baby.

Contraindications

1. Hypersensitivity: People with known hypersensitivity to amlodipine or other dihydropyridine calcium antagonists should avoid its use.
2. Heart failure: Patients with heart failure, especially those with low blood pressure, should take amlodipine with caution.
3. Angina: In patients with anginapectoris(angina), especially with attacks of unstable angina, the use of amlodipine requires caution.
4. Acute myocardial infarction: Amlodipine may be used with caution in the first few weeks after acute myocardial infarction.
5. Severe hepatic dysfunction: Patients with severe hepatic dysfunction should take amlodipine with caution due to possible intensification of the drug action.
6. Pregnancy and breastfeeding: The use of amlodipine during pregnancy may be limited and should be used only when absolutely necessary. Therefore, the decision to use amlodipine during pregnancy should be made by a physician.
7. Children: Data on the efficacy and safety of amlodipine in children are insufficient, therefore use in children requires special attention and supervision by a physician.
8. Aging: In elderly patients, the use of amlodipine may be limited due to possible enhancement of its hypotensive effect and increased risk of orthostatic hypotension.
9. Combination withother medicines: The use of amlodipine in combination with certain other medicines, such as CYP3A4 inhibitors or beta-adrenoblockers, may require dose adjustment and careful monitoring.

Side effects Amlodipine

1. Dizziness and feeling of weakness: Many patients experience dizziness or feeling of weakness at the beginning of taking amlodipine. These symptoms usually go away on their own as the body adapts to the drug.
2. Leg swelling: One of the most common side effects of amlodipine is leg swelling. They may appear as swelling and edema of the legs or lower legs. In some cases, the swelling may spread to other parts of the body.
3. Headache: Some patients may experience headaches or worsening of existing headaches while taking amlodipine.
4. Drowsiness and fatigue: Some patients may experience drowsiness or fatigue while taking amlodipine.
5. Digestive disorders: Gastrointestinal side effects such as nausea, vomiting, constipation or diarrhea may occur.
6. Heart palpitations: In some patients, taking amlodipine may cause a sensation of palpitations or palpitations.
7. Peripheral neurologic symptoms: In rare cases, amlodipine may cause nervous system side effects such as paresthesias (tingling or numbness) in the extremities.

Overdose

1. Severe decrease in blood pressure: Amlodipine, as a calcium channel blocker, can cause a significant decrease in blood pressure in overdose. This can lead to hypotonic crisis, fainting and even shock.
2. Tachycardia or bradycardia: Abnormal heart rhythms may occur as a result of amlodipine overdose. This may include a quickening of the heart rate (tachycardia) or a slowing of the heart rate (bradycardia).
3. Hyperkalemia: Amlodipine overdose may lead to increased blood potassium levels (hyperkalemia), especially in patients with impaired renal function.
4. Central nervous system depression: There is a risk of developing central nervous system depression, including drowsiness, decreased level of consciousness, coma, and even seizures.
5. Othersymptoms: Other possible symptoms of amlodipine overdose may include dizziness, headache, nausea, vomiting, diarrhea, etc.

Interactions with other drugs

1. CYP3A4 enzyme inhibitors: CYP3A4 enzyme inhibitors such as ketoconazole, itraconazole, clarithromycin, erythromycin, ritonavir and other antiretroviral drugs may increase blood levels of amlodipine, which may lead to an increase in its hypotensive effect and an increased risk of side effects such as edema and dizziness.
2. CYP3A4 enzyme inducers: CYP3A4 enzyme inducers such as rifampicin, carbamazepine, phenytoin, phenobarbital and herbal preparations containing tutti frutti may reduce blood levels of amlodipine, which may lead to a decrease in its hypotensive effect and an increased risk of cardiovascular events.
3. Beta-adrenoblockers: The combination of amlodipine with beta-adrenoblockers may increase the hypotensive effect and decrease the heart rate. This may lead to a decrease in heart rate and an increased risk of bradycardia.
4. Other antihypertensive drugs: Combined use of amlodipine with other antihypertensive drugs, such as ACE inhibitors or diuretics, may lead to increased hypotensive effect and increased risk of orthostatic hypotension.
5. Statins: Statins such as atorvastatin and simvastatin may increase the risk of myopathy when combined with amlodipine, especially when used concomitantly at high doses.