Amlodipine is an oral dihydropyridine calcium channel blocker. Compared to nifedipine and other medications in the dihydropyridine class, amlodipine has the longest half-life at 30 to 50 hours. The benefit of such a long half-life is the ability to have once-daily dosing. Amlodipine is available as amlodipine besylate, which was initially approved in 1987 by the Food and Drug Administration (FDA).
Double-blind, placebo-controlled, randomized studies have shown statistically significant placebo-corrected reductions in supine and standing blood pressures 24 hours after the administration of amlodipine
Coronary Artery Disease
Amlodipine can be used as monotherapy or in combination with several different medications to manage hypertension or CAD in patients. Common combinations include:
Normally, vascular smooth muscle contraction is initiated when calcium enters the cell via voltage-dependent L-type calcium channels. The calcium binds to intracellular calmodulin which subsequently binds to and activates myosin light-chain kinase (MLCK). MLCK is responsible for the phosphorylation of myosin light-chain, ultimately leading to muscle contraction and vasoconstriction. The vascular smooth muscle contraction is further amplified by calcium-induced calcium release from the sarcoplasmic reticulum. This sequence of events leads to a decreased vascular cross-sectional area, increased vascular resistance, and increased blood pressure.
Amlodipine works by blocking the voltage-dependent L-type calcium channels, thereby inhibiting the initial influx of calcium. Reduced intracellular calcium leads to decreased vascular smooth muscle contractility, increased smooth muscle relaxation, and resultant vasodilation. Ultimately, this causes a decrease in blood pressure.
Amlodipine’s role in relieving stable angina is due to the lowering of afterload secondary to its vasodilatory and antihypertensive properties. Reducing afterload leads to a lowering of myocardial oxygen demand at any level of exertion as the heart does not need to work as hard to pump blood into systemic circulation.
Amlodipine also alleviates prinzmental or variant angina by blocking coronary spasm and restoring blood flow in the coronary arteries.
Amlodipine is primarily administered orally and is available as 2.5-mg, 5-mg, and 10-mg tablets. For pediatric patients and elderly patients with difficulty swallowing, suspensions created from oral tablets are available.
CAD, Chronic Stable Angina, Prinzmental Angina, CAD Documented by Angiography and Without Heart Failure or Ejection Fraction less than 40%
Patients with Hepatic Impairment
The major adverse effects of amlodipine include peripheral edema, heart failure, pulmonary edema, flushing, dizziness, headache, drowsiness, skin rash, nausea, and abdominal pain. In controlled clinical trials, edema, dizziness, flushing, and palpitations were observed in a dose-dependent manner. At a dose of 10 mg, the incidence of edema, dizziness, flushing, and palpitations was 10.8%, 3.4%, 2.6%, and 4.5%, respectively. The incidence of a headache, fatigue, nausea, and abdominal pain was 7.3%, 4.5%, 2.9%, and 1.6%, respectively.
Coadministration of amlodipine and clarithromycin or erythromycin has been reported to increase the risk of hypotension and acute kidney injury due to decreased metabolism by CYP3A4. Additionally, when amlodipine is used together with high doses of statins, there is an increased risk for myopathy and rhabdomyolysis. 
Amlodipine is absolutely contraindicated in patients with known hypersensitivity to amlodipine or its components. Amlodipine is relatively contraindicated and should be used with caution, in patients with cardiogenic shock, severe aortic stenosis, unstable angina, severe hypotension, heart failure, and hepatic impairment. In cardiogenic shock, the heart cannot pump effectively, and this situation is exacerbated by inhibiting the influx of calcium ions into cardiac cells. In severe aortic stenosis, amlodipine can cause ventricular collapse and dysfunction. In unstable angina, amlodipine causes a reflexive increase in cardiac contractility, which increases myocardial oxygen demand and worsens the ischemia. In patients with severe hypotension, amlodipine can result in a further drop in blood pressure, hypoperfusion to vital organs, and syncope. Patients who have heart failure may experience pulmonary edema, shortness of breath, and dyspnea with amlodipine. Lastly, patients with hepatic impairment may not be able to metabolize amlodipine, leading to a longer half-life adequately 
In general, laboratory monitoring is not required for patients taking amlodipine. Since amlodipine is an antihypertensive medication, clinicians and patients should regularly measure blood pressure to achieve target levels as per the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines. Furthermore, patients should be monitored for adverse side effects such as peripheral edema, dizziness, flushing, among others.
Amlodipine overdose and toxicity can lead to massive vasodilation, hypotension, and reflexive tachycardia to compensate. Prolonged systemic hypotension can progress to shock and even death. The hypotension is usually alleviated by intravenous (IV) fluid resuscitation, calcium salts, and vasopressor therapy with dopamine or norepinephrine. High-dose insulin is also sometimes administered as it has been shown to lower mortality and improve hemodynamics. Electrocardiographic results, vital signs, kidney function, urine output, and electrolytes are continually monitored during an overdose.
Healthcare workers including nurse practitioners should be familiar with the indications and contraindications of amlodipine. Compared to nifedipine and other medications in the dihydropyridine class, amlodipine has the longest half-life at 30 to 50 hours. The benefit of such a long half-life is the ability to have once-daily dosing. The drug can cause severe hypotension and thus it is recommended that the patient be gradually titrated with an initial low dose. Long-term patient monitoring is necessary to determine its effectiveness.