Hydroxyzine
Hydroxyzine
Generic Name
Hydroxyzine
Mechanism
- Competitive H1‑receptor blockade in the central and peripheral nervous system → reduces histamine‑mediated neurotransmission.
- Serotonin (5‑HT3) receptor antagonism contributes to anti‑emetic activity.
- Inhibition of muscarinic cholinergic receptors and voltage‑gated calcium channels enhances the sedative effect.
- Central histamine blockade decreases cortical arousal, producing anxiolysis.
Pharmacokinetics
| Parameter | Intravenous | Oral (25 mg) |
| Absorption | Rapid, peak concentration within 10 min | 85‑95 % bioavailability, Tmax 1–2 h |
| Distribution | Volume ~0.6 L/kg; highly protein‑bound (≈ 50 %) | Blood‑brain barrier penetration is extensive |
| Metabolism | Hepatic via CYP3A4 → active metabolite *desmethyl‑hydroxyzine* | Same pathway; 50‑70 % 1‑hydroxy‑hydroxyzine (inactive) |
| Half‑life | 1 h (IV) | 20–25 h (oral) |
| Elimination | Renal (~30 %) & biliary | Renal excretion of conjugates, ~45–60 % unchanged |
| Drug interactions | CYP3A4 inhibitors ↑ levels; CYP3A4 inducers ↓ efficacy | Elevated CNS depression when combined with benzodiazepines, alcohol |
Indications
- Acute allergic reactions (urticaria, angioedema) – as an antihistamine.
- Anxiety pre‑procedure or chronic – short‑term anxiolytic therapy.
- Premenstrual tension syndrome (PMTS) – symptomatic relief.
- Nausea and vomiting – antiemetic adjunct (esp. chemotherapy).
- Sleep disorders – occasional short‑term sleep aid.
- Adjunct in postoperative care – for sedation and anti‑emetic purposes.
Contraindications
- Absolute: hypersensitivity to hydroxyzine or any excipients; cholinergic crisis; asthma with acute bronchospasm.
- Relative:
- Asthma, COPD, bronchiectasis, emphysema (risk of bronchospasm).
- Narrow‑angle glaucoma, prostatic hypertrophy, urinary retention (antimuscarinic effects).
- Severe hepatic impairment (altered metabolism).
- Pediatric and geriatric (increased sensitivity to CNS depression).
- Warnings:
- CNS depression: caution when combined with alcohol, benzodiazepines, opioids.
- Cardiac effects: QT prolongation in high doses or CNS‑lethal doses; monitor EKG in patients on other QT‑prolonging drugs.
- Pregnancy/Lactation: Category C; limited data—use only if benefits outweigh risks; minimal transfer into breast milk.
Dosing
| Population | Dose | Route | Frequency | Notes |
| Adults (all indications) | 25–50 mg PO | Oral | 1–4 × daily | Prefer 25 mg; titrate to response. |
| Adults (anxiety/PMTS) | 150 mg/day split 3× | Oral | Once every 8 h | Use with caution; monitor for sedation. |
| Children 6–12 yrs | 25 mg PO | Oral | 1–2 × daily | Avoid >4 × daily. |
| Pediatric Intramuscular**: 50 mg IM for immediate anti‑emetic or anxiolytic effect; onset ~5‑10 min.
Adverse Effects
Common (≥10 %):
• Drowsiness, fatigue
• Dry mouth, blurred vision, constipation
• Headache, dizziness
Less common (1–10 %):
• Hypotension, tachycardia (early dosage)
• Visual disturbances (diplopia)
• Confusion, euphoria
Serious (≤1 %):
• Severe CNS depression (coma) – especially with concomitant CNS depressants.
• Severe hypotension (rare).
• Serotonin syndrome (with serotonergic drugs).
• Rash, anaphylaxis (hypersensitivity).
Monitoring
- CNS: level of sedation, responsiveness (for patients on benzodiazepines, opioids).
- Cardiac: EKG for QT interval in patients on other QT‑prolonging agents.
- Renal/Liver: baseline function if chronic therapy >1 month.
- Therapeutic Response: anxiety scores, allergic symptom diaries, nausea rating scales.
Clinical Pearls
- Sedation vs. Antihistamine: Hydroxyzine’s antimuscarinic side‑effects can mimic anticholinergic toxicity; distinguish from true anticholinergic agents by lack of tachycardia and normal pupil size.
- Pre‑operative Use: A single 25‑mg oral dose 2 h pre‑op reduces intra‑operative nausea and improves patient cooperation; avoid pre‑op doses >50 mg due to risk of respiratory depression in older adults.
- Combination with Antipsychotics: When added to atypical antipsychotics (e.g., clozapine), monitor for additive QT prolongation—consider baseline and follow‑up EKG.
- Drug–Drug Interactions: Co‑administration with SSRIs, SNRIs, or MAOIs can precipitate serotonin syndrome; cautious titration or avoidance recommended.
- Drug Monitoring in Renal Failure: Even with reduced clearance, the parent drug is predominantly eliminated unchanged; extend dose interval in CrCl *References*: For detailed pharmacology, refer to Goodman & Gilman's *The Pharmacological Basis of Therapeutics*, 14th ed., and the latest CECO/EMA Drug Summary for Hydroxyzine.
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