Hydroxyzine

BRAND NAMES:

Atarax – In general it is available in the form of tablets and oral suspensions in which the major active ingredient is hydroxyzine. Hydroxyzine hydrochloride syrup 10mg and Hydroxyzine hydrochloride 2mg tablets are also available for the treatment.

Vistaril – Vistaril capsules 25 mg and 50mg contain hydroxyl pamoate equivalent to hydroxyzine hydrochloride and are also available in the form of an oral suspension of hydroxyzine pamoate equivalent to 25mg of hydroxyzine hydrochloride.

MECHANISM OF ACTION:

Histamine increases vascular permeability, allowing fluid to move from capillaries into surrounding tissues. Overall, this causes greater edema and dilatation of vessels. Antihistamines counteract this action by blocking the H1 receptors. The clinical effect is a decrease in allergy symptoms and other associated problems.

First-generation antihistamines readily penetrate the blood-brain barrier and antagonize H1 receptors, resulting in a distinct therapeutic and adverse impact profile compared to second-generation antihistamines, which exclusively bind to peripheral histamine receptors. 

The pharmacological effects of first-generation antihistamines last around 4 to 6 hours. In contrast, second-generation antihistamines have a half-life ranging from 12 to 24 hours. Both are metabolized by the liver via the P450 cytochrome system. 

Parietal cells in the gastrointestinal tract release hydrochloric acid. Acetylcholine, gastrin, and histamine all influence their activity. Histamine is secreted by enterochromaffin-like cells. When histamine binds to the H-2 receptors on parietal cells, cyclic adenosine monophosphate rises, which activates protein kinase A. This activity causes phosphorylation of the proteins involved in hydrogen ion transport. Thus, elevated histamine causes a rise in stomach acid.

Antihistamines that target the H2 receptor stop the entire process and lower stomach acid.

PHARMACOKINETICS:

Absorption: The absolute bioavailability of hydroxyzine has yet to be determined, as intravenous formulations are unavailable due to the danger of hemolysis. Hydroxyzine is quickly absorbed from the gastrointestinal system after oral treatment, reaching its peak plasma concentration around 2 hours later.

Distribution: The average distribution volume is 16.0± 3.0 liters per kilogram. The skin has higher amounts than the plasma.

Metabolism: Hydroxyzine is metabolized in the liver via CYP3A4 and CYP3A5. While the exact metabolic destiny of hydroxyzine is unknown, the major and active metabolite produced by the oxidation of its alcohol component to a carboxylic acid is cetirizine, a second-generation antihistamine. Hydroxyzine is most likely degraded into multiple metabolites, although precise structures and routes have yet to be identified in humans.

Excretion: Approximately 70%of hydroxyzine active metabolite, cetirizine is excreted unchanged in the urine. The precise extent of renal and fecal excretion in humans has not been determined. 

PHARMACODYNAMICS:

Hydroxyzine lowers histamine activity, which relieves allergy symptoms like pruritus. Because of its off-target effects, it can be used as a sedative, anxiolytic, and antiemetic in some disorders. 

Hydroxyzine is a somewhat fast-acting medicine, with an onset time of 15 to 60 minutes and a duration of 4-6 hours. Hydroxyzine may enhance the effects of central nervous system depressants following general anesthesia; patients taking hydroxyzine should be given reduced doses of any CNS depressants that are required. Based on postmarketing reports of rare events such as Torsade de Pointes, cardiac arrest, and sudden death, hydroxyzine has been demonstrated to prolong the QT/QTc interval and should be used with caution in individuals who are at a higher risk of QTc prolongation. 

DOSAGE AND ADMINISTRATION:

Antihistamine drugs are often delivered orally in the form of tablets. It is also feasible to administer intravenously or intramuscularly. 

The hydroxyzine oral tablet dosage prescribed by your doctor will be determined by a variety of factors. Factors to consider include the patient's age, ailment severity, and medical history

Hydroxyzine oral tablets come in three strengths: 10mg, 25mg, and 50mg. 

DRUG INTERACTIONS:

Although certain drugs should never be combined, two separate medicines may be administered together even if an interaction occurs.

Hydroxyzine interacts with a variety of drugs and substances. 

• Opioids - hydrocodone, acetaminophen, or oxycodone

• Benzodiazepines - alprazolam or clonazepam.

• Sleep medications - zolpidem or eszopiclone

• Interactions with these drugs may raise the risk of heart-related issues.

• Amiodarone Antibiotics - azithromycin or ciprofloxacin

• Antipsychotics - aripiprazole or quetiapine

FOOD INTERACTIONS:

Avoid alcohol. Co-administration with alcohol may exacerbate hydroxyzine's unfavorable CNS effects. 

Avoid grapefruit products. Co-administration with grapefruit decreases hydroxyzine metabolism and may result in higher serum.

CONTRAINDICATIONS:

Certain antihistamines have possible cardiotoxic side effects and are generally contraindicated in any patient with QTc prolongation. Patients using other QTc prolongation medicines must be closely monitored for further lengthening of the QTc interval because of the danger of potentially deadly cardiac arrhythmias. 

Using in pregnant women is a relative contraindication. Women who are lactating should avoid using antihistamines. 

Patients with poor renal or hepatic function should exercise caution when using antihistamines. 

Hypertension, cardiovascular illness, urine retention, and elevated ocular pressure are all relative contraindications to using antihistamines.

SIDE EFFECTS:

A drug may induce various undesirable consequences, such as include 

• Chest discomfort.

• Symptoms include cough and dizziness. 

• Fainting 

• Fast heartbeat. 

• itching or skin rash 

• Slow heart rate. 

• Swelling around the eyes 

Symptoms: difficulty breathing, weakness. 

OVERDOSE:

Taking more than the prescribed dosage of hydroxyzine oral pills can result in serious negative effects. An overdose of hydroxyzine may cause mild symptoms such as nausea and vomiting. 

• Fever 

• Sleepiness 

• High doses of hydroxyzine can induce severe overdose symptoms, including seizures. 

• Breathing problems 

• Low blood pressure. 

• Coma

TOXICITY:

Hydroxyzine competes with histamine for binding to H1 receptor sites on the effector cell surface, reducing histaminic edema, flare, and pruritus. Hydroxyzine's sedative activities occur at subcortical levels of the CNS. In addition to its central anticholinergic properties, hydroxyzine may be beneficial as an antiemetic. 

STORAGE:

Hydroxyzine oral pills should be kept at 68°F to 77°F (20°C to 25°C) in a firmly sealed container away from light. Avoid storing in wet or moist environments.