Overview
Definition:
Antihistamines are medications used to block the action of histamine, a substance in the body that plays a key role in allergic reactions
They are broadly classified into first-generation (sedating) and second-generation (non-sedating) agents, with distinct pharmacological profiles and clinical applications, particularly in pediatric populations.
Epidemiology:
Allergic rhinitis and urticaria are common conditions in children, affecting 10-30% of pediatric populations worldwide
The choice of antihistamine significantly impacts symptom control and quality of life for these patients.
Clinical Significance:
Appropriate selection of antihistamines in children is crucial for effective management of allergic diseases while minimizing adverse effects
Differentiating between sedating and non-sedating agents is essential for optimizing treatment, preventing somnolence-related issues, and improving adherence, particularly in a competitive examination context for DNB and NEET SS aspirants.
Classification And Mechanism
First Generation Sedating:
These agents readily cross the blood-brain barrier, leading to central nervous system (CNS) effects such as drowsiness, sedation, and impaired cognitive function
They also have anticholinergic, antiserotonergic, and antiemetic properties
Examples include diphenhydramine, chlorpheniramine, hydroxyzine, and promethazine.
Second Generation Non Sedating:
These are peripheral H1 receptor antagonists with significantly reduced affinity for CNS H1 receptors due to their lower lipophilicity and/or being substrates for efflux transporters like P-glycoprotein
This results in minimal to no sedation
Examples include cetirizine, levocetirizine, loratadine, desloratadine, fexofenadine, and azelastine.
Mechanism Of Action:
Both generations competitively antagonize H1 receptors, thereby preventing the effects of histamine released from mast cells and basophils during an allergic response
These effects include vasodilation, increased vascular permeability, smooth muscle contraction, and stimulation of sensory nerve endings, leading to symptoms like itching, sneezing, rhinorrhea, and urticaria.
Clinical Presentation Of Allergic Conditions
Allergic Rhinitis:
Nasal pruritus
Sneezing
Rhinorrhea (clear, watery discharge)
Nasal congestion
Post-nasal drip
Ocular symptoms (pruritus, redness, watering)
Cough.
Urticaria:
Pruritic, erythematous, raised wheals (hives)
Transient nature of individual lesions (lasting <24 hours), though new lesions may appear as old ones resolve
Angioedema (swelling of deeper tissues, often periorbital or lips).
Atopic Dermatitis:
Pruritus (often severe, especially at night)
Erythematous, eczematous lesions
Xerosis (dry skin)
Secondary excoriations and infections due to scratching.
Comparative Efficacy And Adverse Effects
Efficacy:
Both sedating and non-sedating antihistamines are effective in managing symptoms of allergic rhinitis and urticaria
Second-generation agents provide comparable or superior efficacy for nasal and ocular symptoms with improved safety profiles for daytime use.
Sedating Adverse Effects:
Drowsiness, sedation, impaired psychomotor performance, decreased school performance, anticholinergic effects (dry mouth, blurred vision, urinary retention, constipation), dizziness, paradoxical excitation in young children.
Non Sedating Adverse Effects:
Generally well-tolerated
Mild headache, dry mouth, and fatigue can occur but are less frequent and less severe than with first-generation agents
Cardiac arrhythmias (QT prolongation) are a concern with some older agents but generally not with currently recommended pediatric second-generation antihistamines.
Indications And Contraindications In Children
Sedating Indications:
Severe allergic reactions where rapid onset of action and anxiolytic effects are desired (e.g., adjunctive for anaphylaxis)
Insomnia associated with itching in nocturnal urticaria
Sedation adjunct for procedures in older children (e.g., hydroxyzine).
Non Sedating Indications:
Chronic allergic rhinitis, perennial allergic rhinitis, seasonal allergic rhinitis
Chronic urticaria
Allergic conjunctivitis
Atopic dermatitis (adjunctive therapy).
Contraindications:
Hypersensitivity to the specific drug
Use with caution in infants under 6 months (especially sedating agents)
Narrow-angle glaucoma and urinary retention (anticholinergic effects of sedating agents)
Bronchopulmonary disease (sedating agents can thicken bronchial secretions).
Drug Selection And Dosing In Pediatrics
First Generation Dosing:
Diphenhydramine: 1.25 mg/kg/dose PO/IV/IM every 6-8 hours (max 5 mg/kg/day)
Chlorpheniramine: 0.35 mg/kg/day PO divided every 6 hours (max 12 mg/day)
Hydroxyzine: 0.5-1 mg/kg/dose PO QID (max 2 mg/kg/day or 100 mg/day).
Second Generation Dosing:
Cetirizine: Age 2-6 years: 2.5 mg once daily
Age >6 years: 5-10 mg once daily
Levocetirizine: Age 6-11 years: 2.5 mg once daily
Age >12 years: 5 mg once daily
Loratadine: Age 2-12 years: 5 mg once daily (tablets/syrup)
Age >12 years: 10 mg once daily.
Considerations For Selection:
For daytime symptom control and activities requiring alertness, non-sedating agents are preferred
Sedating agents may be considered for nocturnal pruritus or when a sedating effect is beneficial
Always consider the child's age, weight, co-morbidities, and potential drug interactions.
Key Points
Exam Focus:
DNB/NEET SS exam questions often focus on distinguishing between the two classes, identifying common pediatric allergens, and appropriate dosing for allergic rhinitis and urticaria
Understanding CNS penetration and anticholinergic side effects is critical.
Clinical Pearls:
Advise parents about potential sedation with first-generation antihistamines, especially regarding school performance and operating machinery (if applicable to older adolescents)
For chronic allergic conditions, a once-daily non-sedating antihistamine is often the first-line choice.
Common Mistakes:
Using sedating antihistamines for routine daytime allergy management, leading to impaired academic performance
Inappropriate dosing based on adult recommendations
Overlooking non-pharmacological management strategies for allergic diseases.