What is the recommended initial treatment for pharmacology practical screening of anti-histaminic (antihistamine) drugs?

Pharmacologic Screening of Antihistamine Drugs

Second-generation antihistamines are the recommended initial treatment for pharmacology practical screening of antihistaminic drugs due to their superior safety profile and reduced sedative effects compared to first-generation antihistamines. 1

Classification of Antihistamines

First-Generation Antihistamines

• Have significant potential to cause sedation, performance impairment, and anticholinergic effects (dry mouth, urinary retention) 1
• Examples include diphenhydramine, chlorpheniramine, and brompheniramine 2
• Cross the blood-brain barrier extensively, affecting cognitive function and psychomotor performance 3
• Should be avoided as first-line therapy due to safety concerns and potential for impairment 1, 2

Second-Generation Antihistamines

• Generally preferred over first-generation antihistamines for allergic conditions 1
• Cross the blood-brain barrier to a significantly smaller extent than their predecessors 3
• Can be further classified based on sedative properties:
  • Non-sedating (<20% brain H₁ receptor occupancy): fexofenadine, bilastine 4
  • Less-sedating (20-50% brain H₁ receptor occupancy): loratadine, desloratadine, cetirizine 4
  • Some may cause sedation at higher than recommended doses 1

Recommended Screening Protocol

Step 1: Initial Selection of Antihistamines

• Begin with second-generation antihistamines due to better safety profile 1, 3
• Prioritize testing non-sedating options first (fexofenadine, loratadine, desloratadine) 1
• These agents have been extensively studied for efficacy and safety 3

Step 2: Comparative Assessment

• Compare antihistamines based on:
  • Sedative properties at recommended doses 1
  • Time to maximum concentration (cetirizine has shortest time) 1
  • Duration of action (desloratadine has longest elimination half-life at 27 hours) 1
  • Potential for drug interactions (mizolastine has significant interactions) 1

Step 3: Special Population Considerations

• For hepatic impairment: Avoid mizolastine; use loratadine and desloratadine with caution 1, 5
• For renal impairment: Avoid acrivastine; reduce doses of cetirizine and levocetirizine 1
• For pediatric screening: Consider age-appropriate formulations and dosing 6
• For pregnancy: Generally avoid all antihistamines if possible, especially in first trimester 1

Evaluation Parameters

Efficacy Assessment

• Measure reduction in histamine-induced wheal and flare response 5
• Evaluate onset of action (typically within 1 hour for most antihistamines) 5
• Assess duration of effect (up to 24 hours for many second-generation agents) 5
• Compare efficacy for specific symptoms (rhinorrhea, sneezing, itching, congestion) 1

Safety Assessment

• Monitor for sedation using standardized scales 2
• Evaluate cognitive function and psychomotor performance 3
• Assess QT interval prolongation risk, particularly with higher doses 5
• Screen for anticholinergic effects 1, 2

Common Pitfalls and Caveats

• Do not rely solely on subjective reports of sedation, as impairment may occur without perceived drowsiness 2
• Be aware that some patients (approximately 6%) may be poor metabolizers of certain antihistamines like desloratadine 5
• Higher prevalence of poor metabolizers exists among Black populations (17%) compared to Caucasians and Hispanics (2%) 5
• Avoid increasing doses above recommended levels without considering potential for increased adverse effects 1
• Remember that intranasal antihistamines can be considered as alternatives to oral formulations but may still cause systemic effects 1

Specific Recommendations for Different Antihistamine Classes

Oral Antihistamines

• Fexofenadine: Offers excellent balance of effectiveness and safety with minimal sedation even at higher doses 7
• Cetirizine: Most potent antihistamine but may cause sedation in about 10% of patients 7
• Loratadine and desloratadine: Generally non-sedating at recommended doses 1
• Patients should be offered at least two non-sedating options as responses vary between individuals 1

Intranasal Antihistamines

• May be considered for first-line treatment of allergic and non-allergic rhinitis 1
• Equal to or superior to oral second-generation antihistamines for seasonal allergic rhinitis 1
• Have clinically significant effect on nasal congestion 1
• Generally less effective than intranasal corticosteroids 1
• Can cause systemic absorption and potential sedation 1