What Are They, Mechanism of Action, Indications, Side Effects, and More

Author:Anna Hernández, MD

Editors:Ahaana Singh,Lisa Miklush, PhD, RN, CNS

Illustrator:Aileen Lin

What are dihydropyridines?

Dihydropyridines are a type of calcium channel blocker (CCB), which refer to a group of medications that block calcium channels located in the muscle cells of the heart and arterial blood vessels, thereby reducing the entry of calcium ions into the cell. By blocking these channels, CCBs promote blood vessel dilation (i.e. vasodilation), as well as changes in heart function, including reductions in heart rate, strength of contractility, and speed of conduction within the heart. 

Overall, these effects contribute to a drop in blood pressure and a decrease in the oxygen requirements of the heart. Because of these cardiovascular effects, CCBs can be used to treat hypertension (high blood pressure), among other heart problems, including angina (chest pain that results from a compromised oxygen supply to the heart muscle) and cardiac arrhythmias (disturbances in the heart rhythm).

Which calcium channel blockers are dihydropyridines?

According to their main site of action, CCBs can be categorized into two main classes—dihydropyridines and non-dihydropyridines—with different uses and side effects. Dihydropyridines act predominantly on blood vessels to promote vasodilation without having much of a direct effect on cardiac function. They include medications that end with the suffix “-dipine”, such as nifedipine, nicardipine, nimodipine, and amlodipine, to name a few. On the other hand, non-dihydropyridines have a greater effect on the heart but are less effective in promoting vasodilation. Non-dihydropyridines include fewer medications, such as verapamil and diltiazem.

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How do dihydropyridines work?

Dihydropyridines work by binding to and blocking voltage-gated L-type calcium channels found on smooth muscle cells of arterial blood vessels. Usually, these channels open in response to an electrical signal, or action potential, hence the name “voltage-gated” L-type calcium channels. These calcium channels are responsible for regulating the entry of extracellular calcium into muscle cells, which in turn stimulates muscular contraction of blood vessels. By blocking these channels, dihydropyridines are able to decrease blood vessel contraction, leading to a sustained vasodilation. In turn, vasodilation reduces vascular resistance of arterial blood vessels, leading to a drop in blood pressure.

What are dihydropyridines used for?

Dihydropyridines can be used for a variety of conditions that relate to increased vascular resistance, or increased contraction of blood vessels. Most commonly, they are used to treat hypertension by way of vasodilation, or the dilation of arterial blood vessels. Although they can be used in most individuals, they are most effective in people of Afro-Caribbean descent, as well as in older adults, both in which high systolic blood pressure is typically a result of large blood vessel stiffness. Additionally, some dihydropyridines, like nifedipine, can be given to treat high blood pressure in pregnant individuals. 

In addition, long-acting dihydropyridines can be used to treat vasospastic or Prinzmetal angina, which is caused by the narrowing of the blood vessels that supply blood to the heart (i.e. coronary arteries). In such cases, dihydropyridines can dilate the coronary arteries, increasing blood flow to the heart muscle. Moreover, they can also be used to prevent stable angina, a sudden chest pain that results from a compromised oxygen supply to the heart. 

Dihydropyridines can also be used to treat Raynaud’s syndrome, a medical condition caused by the narrowing of the small arteries of the fingertips when exposed to cold temperatures or stress. Some dihydropyridines, such as nifedipine, can also be used to slow down uterine contractions in pregnant individuals at risk of preterm birth, thereby reducing the risk of neonatal complications. Lastly, nimodipine can be used to prevent cerebral vasospasm (a sudden narrowing of the cerebral blood vessels), a serious complication that can arise after the development of a subarachnoid brain hemorrhage, or the bleeding within the protective membranes that surround the brain and spinal cord.

What are the side effects of dihydropyridines?

Dihydropyridines are generally well tolerated amongst most individuals. However, in some cases, they may amplify their own effects, causing unwanted side effects. For example, excessive vasodilation can result in low blood pressure, headaches, dizziness, and facial flushing. Similarly, short-acting dihydropyridines can cause a sudden drop in blood pressure, which can cause activation of the sympathetic nervous system, leading to reflex tachycardia (an increased heart rate). In turn, this can lead to palpitations (the uncomfortable sensation of the heart pounding inside the chest). Another common side effect is ankle swelling, which can result from increased leakage of fluid from blood vessels. Finally, gingival hyperplasia (enlargement of the gums) is a rare side effect that can be seen with certain dihydropyridines, such as nifedipine.

Are some people allergic to dihydropyridines?

Treatment with dihydropyridines can occasionally cause allergic reactions in predisposed individuals. Although rare, severe allergic reactions can cause angioedema, or the swelling of the soft tissues under the skin, as well as adverse skin reactions, ranging from mild rashes to severe skin conditions.

What are the most important facts to know about dihydropyridines?

Dihydropyridines (e.g. nimodipine, nifedipine, amlodipine) are a type of calcium channel blocker, a group of medications that block calcium channels located in the muscle cells of the heart and blood vessels. Because of their selective effect on arterial blood vessels, dihydropyridines are mainly used to decrease vascular resistance and blood pressure, and therefore are used to treat hypertension. Other uses of dihydropyridines include preventive treatment of stable angina, Raynaud’s syndrome, and cerebral vasospasm. Possible side effects include headaches or dizziness, palpitations, ankle swelling, and, rarely, enlargement of the gums. Although rare, allergic reactions have been described in predisposed individuals.

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Related links

Angina pectoris
Calcium channel blockers
Muscle contraction
Raynaud's disease
Subarachnoid hemorrhage

Resources for research and reference

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Katzung, B. G., Masters, S. B., & Trevor, A. J. (2012). Basic & Clinical Pharmacology. New York: McGraw-Hill Medical.

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Kuruvilla, M. E. & Sanan, N. (2018). Amlodipine-Induced Angioedema: An Unusual Complication of a Common Medication. Allergy & Rhinology, 9: 1–3. DOI: 10.1177/2152656718764139

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Williams, B., Mancia, G., Spiering, W., et al. (2018). 2018 ESC/ESH Guidelines For The Management of Arterial Hypertension. European Heart Journal, 39(33): 3021–3104. DOI: 10.1093/eurheartj/ehy339