HBRD Module 2 Infographic | Introduction to Medical Pharmacology

Property	First Generation	Second Generation
Examples	Diphenhydramine, promethazine, hydroxyzine, chlorpheniramine	Loratadine, cetirizine, fexofenadine
CNS penetration	Yes — lipophilic, crosses blood-brain barrier readily	Minimal — less lipophilic; active P-glycoprotein efflux
Sedation	Prominent — limits daytime use	Minimal (fexofenadine least; cetirizine slightly more than others)
Antimuscarinic effects	Yes — dry mouth, urinary retention, blurred vision, constipation	None at therapeutic doses
Dosing frequency	Every 4–6 hours	Once daily
Preferred uses	Motion sickness, short-term insomnia, nighttime pruritus	Allergic rhinitis, chronic urticaria (daytime)

Second Generation

Loratadine / Desloratadine

Minimal sedation; no antimuscarinic effects
Hepatic metabolism to active metabolite desloratadine
No dose adjustment needed in renal impairment
Once daily

Second Generation

Cetirizine / Levocetirizine

Slightly more sedating than loratadine or fexofenadine
Renal elimination unchanged — dose reduction in renal impairment
Levocetirizine is the active enantiomer
Once daily

Second Generation

Fexofenadine

Least sedating — strongest P-glycoprotein efflux
Minimal hepatic metabolism; excreted largely unchanged
Safe in hepatic impairment
Fruit juice reduces absorption — take with water

First Generation — Avoid in Elderly

Diphenhydramine / Promethazine

Strong sedation and antimuscarinic burden
Beers Criteria — avoid in elderly
Overdose: anticholinergic toxidrome
Uses: motion sickness, insomnia, nighttime pruritus

High-Yield Rule — Anaphylaxis

Epinephrine is the only first-line treatment for anaphylaxis. Antihistamines are adjuncts that reduce pruritus and urticaria but do not reverse bronchospasm or hemodynamic collapse. No antihistamine — first- or second-generation — is ever the correct answer to "initial management of anaphylaxis."

H1 Antihistamines: First and Second Generation