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Cyclizine

Cyclizine: A Comprehensive Overview of its Uses, Mechanism, and Side Effects

Introduction

Cyclizine, a first-generation antihistamine, is widely used to treat symptoms related to nausea, vomiting, and dizziness caused by motion sickness, vertigo, and various other conditions. Its antiemetic properties, along with its ability to alleviate motion-induced symptoms, have made it a go-to drug for managing conditions where nausea and dizziness are prominent.

Cyclizine

Cyclizine is an antihistamine, specifically a piperazine derivative, primarily used as an antiemetic and for the management of nausea and vomiting. It is commonly prescribed for motion sickness, postoperative nausea, and other conditions where the prevention of nausea and vomiting is necessary. Although it belongs to the class of first-generation antihistamines, its sedative properties are more pronounced compared to its newer counterparts.

Mechanism of Action

Cyclizine works by antagonizing the action of histamine at H1 receptors in the brain, specifically within the vomiting center of the brainstem. Histamine, a neurotransmitter involved in inflammatory responses, also plays a critical role in the regulation of nausea and vomiting. Cyclizine prevents the binding of histamine to its receptors, thereby reducing the vomiting reflex and alleviating nausea. Additionally, it has mild anticholinergic properties, which also contribute to its antiemetic effects by blocking acetylcholine receptors, another pathway involved in nausea and vomiting. In addition to its antiemetic effects, cyclizine can affect the vestibular system, which is responsible for balance. This makes it effective in treating vertigo and dizziness caused by conditions like benign paroxysmal positional vertigo (BPPV) and Meniere’s disease. By stabilizing the vestibular system, cyclizine helps to reduce the sensations of dizziness and imbalance.

Clinical Uses of Cyclizine

Cyclizine's main use is in the treatment and prevention of nausea, vomiting, and dizziness, particularly in conditions associated with motion sickness and vertigo. However, its clinical applications extend beyond these common uses.

1. Motion Sickness

Motion sickness occurs when there is a discrepancy between visual inputs and sensory information received from the inner ear, resulting in symptoms such as nausea, vomiting, and dizziness. Cyclizine is commonly used to prevent and treat these symptoms, particularly in individuals who experience motion sickness during travel.

2. Postoperative Nausea and Vomiting (PONV)

After surgery, many patients experience nausea and vomiting due to anesthesia or the surgical procedure itself. Cyclizine is often used as part of a multimodal approach to prevent and manage postoperative nausea and vomiting (PONV).

3. Vertigo and Dizziness

Cyclizine is also used in treating dizziness and vertigo related to disorders of the inner ear, such as Meniere’s disease, and conditions like benign paroxysmal positional vertigo (BPPV). It helps relieve the associated nausea and the imbalance caused by disturbances in the vestibular system.

4. Allergic Reactions and Skin Conditions

As a first-generation antihistamine, cyclizine is also useful in alleviating symptoms of allergic reactions, such as itching, rash, and hives. However, its use for these conditions has largely been replaced by newer antihistamines with fewer sedative effects.

Pharmacokinetics of Cyclizine

Understanding how cyclizine is absorbed, distributed, metabolized, and excreted is essential for its proper clinical use.

Absorption: Cyclizine is well-absorbed following oral administration, with peak plasma concentrations typically occurring within 1-2 hours.
Bioavailability: The drug exhibits good bioavailability, although the precise percentage is not well-established in the literature.
Metabolism: Cyclizine is metabolized in the liver, primarily via the cytochrome P450 enzyme system. Its metabolism produces inactive metabolites that are then excreted by the body.
Half-life: The elimination half-life of cyclizine is around 20-30 hours, which is relatively long for a first-generation antihistamine. This allows for once or twice daily dosing.
Excretion: Cyclizine is primarily excreted in the urine, with a small portion eliminated through the feces.

Side Effects and Toxicity

Like all medications, cyclizine is associated with certain side effects. Most of these are related to its antihistamine and anticholinergic properties, which can cause various degrees of sedation, dry mouth, and cognitive impairment, particularly in older adults.

Common Side Effects:

Drowsiness and Sedation: As a first-generation antihistamine, cyclizine can cause significant sedation, making it unsuitable for tasks requiring alertness, such as driving or operating heavy machinery.
Dry Mouth and Throat: Due to its anticholinergic effects, cyclizine can cause a dry mouth, which may be uncomfortable.
Dizziness and Blurred Vision: Although cyclizine helps alleviate dizziness, it may paradoxically cause it in some patients, especially when standing up quickly.
Constipation and Urinary Retention: Its anticholinergic properties can slow gastrointestinal motility and contribute to constipation. It may also lead to urinary retention in susceptible individuals.

Serious Side Effects:

Severe Allergic Reactions: Although rare, some individuals may experience severe allergic reactions, including difficulty breathing and swelling of the face and throat, requiring immediate medical attention.
Cognitive Impairment: Cyclizine, like other first-generation antihistamines, can impair cognitive function and may be especially concerning in elderly patients, potentially increasing the risk of falls or confusion.
Heart-Related Issues: In rare cases, cyclizine may cause arrhythmias or affect the heart's electrical activity, particularly in individuals with pre-existing heart conditions.

Drug Interactions

Cyclizine can interact with other medications, leading to either increased side effects or reduced efficacy. Common interactions include:

Central Nervous System Depressants: When used concurrently with other CNS depressants such as alcohol, benzodiazepines, or opioids, cyclizine’s sedative effects may be amplified.
Anticholinergic Medications: Using cyclizine in combination with other drugs that have anticholinergic effects (such as atropine, antihistamines, or tricyclic antidepressants) may increase the risk of dry mouth, constipation, urinary retention, and cognitive impairment.
CYP3A4 Inhibitors: Since cyclizine is metabolized by the cytochrome P450 enzyme system, particularly CYP3A4, drugs that inhibit this enzyme (such as ketoconazole or grapefruit juice) may increase cyclizine levels in the blood, potentially leading to enhanced side effects.

Considerations and Contraindications

Cyclizine is generally safe for most people, but there are specific populations who should use it with caution or avoid it altogether:

Elderly Patients: Older adults may be more susceptible to the sedative and anticholinergic effects of cyclizine, making them more prone to confusion, dizziness, and falls.
Pregnancy: Cyclizine is classified as a Category C drug by the FDA, meaning it should be used during pregnancy only if the potential benefits outweigh the risks.
Liver and Kidney Disease: People with impaired liver or kidney function should use cyclizine with caution, as reduced metabolic capacity may lead to an increased risk of side effects.

Cyclizine in Clinical Practice

Cyclizine remains an important medication in the clinical management of nausea and vomiting, particularly in cases of motion sickness and postoperative recovery. It is often used in combination with other medications in the management of nausea, and its relatively low cost and well-established safety profile make it a valuable treatment option. However, healthcare providers must remain vigilant in monitoring for potential side effects, especially in elderly patients and those taking other CNS depressants.

Conclusion

Cyclizine is a versatile and effective medication for managing nausea, vomiting, and dizziness, particularly in conditions such as motion sickness, postoperative nausea, and vestibular disorders. While it remains a cornerstone in treating these symptoms, its side effects, including sedation and anticholinergic effects, require careful management. As with any medication, appropriate dosing, awareness of potential interactions, and monitoring for side effects are essential to ensure the safe and effective use of cyclizine in clinical practice.

References:

“Cyclizine.” British National Formulary (BNF). 2020.
Rosenthal, L. J., & Sklar, M. S. (2017). Pharmacology and Therapeutics of Antihistamines. Clinical Pharmacology and Therapeutics, 103(3), 411-416.
“Cyclizine.” Drugs.com. Accessed April 2025.